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Sample records for albuminuria

  1. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  2. CUBN Is a Gene Locus for Albuminuria

    NARCIS (Netherlands)

    Boeger, Carsten A.; Chen, Ming-Huei; Tin, Adrienne; Olden, Matthias; Koettgen, Anna; de Boer, Ian H.; Fuchsberger, Christian; O'Seaghdha, Conall M.; Pattaro, Cristian; Teumer, Alexander; Liu, Ching-Ti; Glazer, Nicole L.; Li, Man; O'Conne, Jeffrey R.; Tanaka, Toshiko; Peralta, Carmen A.; Kutalik, Zoltan; Luan, Jian'an; Zhao, Jing Hua; Hwang, Shih-Jen; Akylbekova, Ermeg; Kramer, Holly; van der Harst, Pim; Smith, Albert V.; Lohman, Kurt; de Andrade, Mariza; Hayward, Caroline; Kollerits, Barbara; Toenjes, Anke; Aspelund, Thor; Ingelsson, Erik; Eiriksdottir, Gudny; Launer, Lenore J.; Harris, Tamara B.; Shuldiner, Alan R.; Mitchell, Braxton D.; Arking, Dan E.; Franceschini, Nora; Boerwinkle, Eric; Egan, Josephine; Hernandez, Dena; Reilly, Muredach; Townsend, Raymond R.; Lumley, Thomas; Siscovick, David S.; Psaty, Bruce M.; Kestenbaum, Bryan; Haritunians, Talin; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Mooser, Vincent; Waterworth, Dawn; Johnson, Andrew D.; Florez, Jose C.; Meigs, James B.; Lu, Xiaoning; Turner, Stephen T.; Atkinson, Elizabeth J.; Leak, Tennille S.; Aasarod, Knut; Skorpen, Frank; Syvaenen, Ann-Christine; Illig, Thomas; Baumert, Jens; Koenig, Wolfgang; Kraemer, Bernhard K.; Devuyst, Olivier; Mychaleckyj, Josyf C.; Minelli, Cosetta; Bakker, Stephan J. L.; Kedenko, Lyudmyla; Paulweber, Bernhard; Coassin, Stefan; Endlich, Karlhans; Kroemer, Heyo K.; Biffar, Reiner; Stracke, Sylvia; Voelzke, Henry; Stumvol, Michael; Maegi, Reedik; Campbell, Harry; Vitart, Veronique; Hastie, Nicholas D.; Gudnason, Vilmundur; Kardia, Sharon L. R.; Liu, Yongmei; Polasek, Ozren; Curhan, Gary; Kronenberg, Florian; Prokopenko, Inga; Rudan, Igor; Aernloev, Johan; Hallan, Stein; Navis, Gerjan; Parsa, Afshin; Ferrucci, Luigi; Coresh, Josef; Shlipak, Michael G.; Bul, Shelley B.; Paterson, Andrew D.; Wichmann, H. -Erich; Wareham, Nicholas J.; Loos, Ruth J. F.; Rotter, Jerome I.; Pramstaller, Peter P.; Cupples, L. Adrienne; Beckmann, Jacques S.; Yang, Qiong; Heid, Iris M.; Rettig, Rainer; Dreisbach, Albert W.; Bochud, Murielle; Fox, Caroline S.; Kao, W. H. L.

    2011-01-01

    Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-

  3. Albuminuria reflects widespread vascular damage. The Steno hypothesis

    DEFF Research Database (Denmark)

    Deckert, T; Feldt-Rasmussen, B; Borch-Johnsen, K;

    1989-01-01

    Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative reti...... to constitute the primary cause of albuminuria and the associated complications. Genetic polymorphism of such enzymes is possibly the main reason for variation in susceptibility.......Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative...... retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.g. heparan sulphate proteoglycan) vulnerable to hyperglycaemia, seem...

  4. Individual long-term albuminuria exposure during angiotensin receptor blocker therapy is the optimal predictor for renal outcome

    NARCIS (Netherlands)

    Felix Kröpelin, Tobias; de Zeeuw, Dick; Holtkamp, Frank Arjan; Packham, David Kenneth; L Heerspink, Hiddo J

    2016-01-01

    BACKGROUND: Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study

  5. Relationship Between Dyslipidemia and Albuminuria in Hypertensive Adults

    Science.gov (United States)

    Lee, Sung-Ho; Kim, Do Hoon; Kim, Yang-Hyun; Roh, Yong Kyun; Ju, Sang Yhun; Nam, Hyo-Yun; Nam, Ga-Eun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo; Park, Yong-Gyu

    2016-01-01

    Abstract This study aimed to estimate the relationship between various lipid abnormalities and albuminuria in hypertensive Korean adults. Data obtained from the Korea National Health and Nutrition Examination Survey in 2011 to 2012 were analyzed. The study included 2330 hypertensive participants. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Dyslipidemia parameters were defined as high TG ≥200 mg/dL, low HDL-C as HDL-C dyslipidemia may be necessary for hypertensive women to address potential albuminuria. PMID:27100412

  6. Number and Frequency of Albuminuria Measurements in Clinical Trials in Diabetic Nephropathy

    DEFF Research Database (Denmark)

    Kröpelin, Tobias F; de Zeeuw, Dick; Andress, Dennis L;

    2015-01-01

    BACKGROUND AND OBJECTIVES: Albuminuria change is often used to assess drug efficacy in intervention trials in nephrology. The change is often calculated using a variable number of urine samples collected at baseline and end of treatment. Yet more albuminuria measurements usually occur. Because...... urine collections per visit were increased. Using all albuminuria measurements at all study visits led to a 4- to 6-fold reduction in sample size to detect a 30% albuminuria-lowering treatment effect with 80% power compared with using baseline and end-of-treatment albuminuria measurements alone...... end point can be significantly improved, leading to smaller sample sizes and less complex trials....

  7. Prevalence and distribution of (micro)albuminuria in toddlers

    NARCIS (Netherlands)

    Gracchi, Valentina; van den Belt, Sophie M; Küpers, Leanne K; Corpeleijn, Eva; de Zeeuw, Dick; Heerspink, Hiddo J L

    2015-01-01

    BACKGROUND: Microalbuminuria is common in the general adult population, with a prevalence of ∼7%, and is an independent indicator of renal and cardiovascular risks. Whether albuminuria is acquired during life (as a result of hypertension/diabetes) or is congenital and already present at birth is unk

  8. Diabetes mellitus, hypertension and albuminuria in rural Zambia

    DEFF Research Database (Denmark)

    Rasmussen, Jon B; Thomsen, Jakúp A; Rossing, Peter;

    2013-01-01

    OBJECTIVE: To assess albuminuria in rural Zambia among patients with diabetes mellitus only (DM group), hypertension only (HTN group) and patients with combined DM and HTN (DM/HTN group). METHODS: A cross-sectional survey was conducted at St. Francis Hospital in the Eastern province of Zambia...... of DM or HTN. RESULTS: A total of 193 participants were included (DM group: n = 33; HTN group: n = 92; DM/HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/HTN group (P group was younger and had lower BMI, WC....... Albumin-creatinine ratio in one urine sample was used to assess albuminuria. Other information obtained included age, sex, body mass index (BMI), waist circumference (WC), blood pressure (BP), glycosylated haemoglobin (HbA1c ), random capillary glucose, time since diagnosis, medication and family history...

  9. Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy

    DEFF Research Database (Denmark)

    Holtkamp, Frank A; de Zeeuw, Dick; de Graeff, Pieter A;

    2011-01-01

    The long-term cardioprotective effect of angiotensin receptor blockers (ARBs) is associated with the short-term lowering of its primary target blood pressure, but also with the lowering of albuminuria. Since the individual blood pressure and albuminuria response to an ARB varies between and withi...

  10. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers

    NARCIS (Netherlands)

    Heerspink, H. J. L.; Johnsson, E.; Gause-Nilsson, I.; Cain, V. A.; Sjostrom, C. D.

    2016-01-01

    Aims: To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. Methods: We conducted a

  11. The Association of Albuminuria With Tubular Reabsorption of Uric Acid : Results From a General Population Cohort

    NARCIS (Netherlands)

    Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.

    2014-01-01

    Background-Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results-Include

  12. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    NARCIS (Netherlands)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-01-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-an

  13. TRPC6 enhances angiotensin II-induced albuminuria.

    LENUS (Irish Health Repository)

    Eckel, Jason

    2011-03-01

    Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.

  14. Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

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    Paccaud Fred

    2011-09-01

    Full Text Available Abstract Background Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. Methods This was a cross-sectional population-based study in Caucasians (n = 5913. Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Results Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P P for trend P P = 0.004 were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. Conclusions In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

  15. Exercise-induced albuminuria is related to metabolic syndrome.

    Science.gov (United States)

    Greenberg, Sharon; Shenhar-Tsarfaty, Shani; Rogowski, Ori; Shapira, Itzhak; Zeltser, David; Weinstein, Talia; Lahav, Dror; Vered, Jaffa; Tovia-Brodie, Oholi; Arbel, Yaron; Berliner, Shlomo; Milwidsky, Assi

    2016-06-01

    Microalbuminuria (MA) is a known marker for endothelial dysfunction and future cardiovascular events. Exercise-induced albuminuria (EiA) may precede the appearance of MA. Associations between EiA and metabolic syndrome (MS) have not been assessed so far. Our aim was to investigate this association in a large sample of apparently healthy individuals with no baseline albuminuria. This was a cross-sectional study of 2,027 adults with no overt cardiovascular diseases who took part in a health survey program and had no baseline MA. Diagnosis of MS was based on harmonized criteria. All patients underwent an exercise test (Bruce protocol), and urinary albumin was measured before and after the examination. Urinary albumin-to-creatinine ratio (ACR) values before and after exercise were 0.40 (0.21-0.89) and 1.06 (0.43-2.69) mg/g for median (interquartile range) respectively. A total of 394 (20%) subjects had EiA; ACR rose from normal rest values (0.79 mg/g) to 52.28 mg/g after exercise (P metabolic equivalents (P < 0.001), higher baseline blood pressure (P < 0.001), and higher levels of fasting plasma glucose, triglycerides, and body mass index (P < 0.001). Multivariate binary logistic regression model showed that subjects with MS were 98% more likely to have EiA (95% confidence interval: 1.13-3.46, P = 0.016). In conclusion, EiA in the absence of baseline MA is independently related to MS.

  16. Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD : The Pro View

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo; Gansevoort, Ron T.

    2015-01-01

    The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but also

  17. Association between Albuminuria and Different Body Constitution in Type 2 Diabetes Patients: Taichung Diabetic Body Constitution Study

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    Cheng-Hung Lee

    2015-01-01

    Full Text Available Objective. Albuminuria in type 2 diabetes mellitus (T2DM patients increases the risk of diabetic nephropathy, the leading cause of end-stage renal disease worldwide. Because albuminuria is modifiable, identifying relevant risk factors could facilitate prevention and/or management. This cross-sectional study investigated whether body constitution (BC independently predicts albuminuria. Method. Patients with T2DM (n=846 received urinalysis, a blood test, and diabetic retinopathy examination. Albuminuria was defined by an elevated urinary albumin/creatinine ratio (≥30 μg/mg. BC type (Yang deficiency, Yin deficiency, and Phlegm stasis was assessed using a body constitution questionnaire (BCQ. Traditional risk factors for albuminuria were also recorded. Odds ratios (ORs of albuminuria for BC were estimated using multivariate logistic regression. Results. Albuminuria was more prevalent in patients with Yang deficiency or Phlegm stasis (both P<0.01. After adjustment, patients with both Yang deficiency and Phlegm stasis exhibited a significantly higher risk of albuminuria (OR = 3.037; 95% confidence interval = 1.572–5.867, and P<0.001. Conclusion. BC is strongly associated with albuminuria in T2DM patients. Using a BCQ to assess BC is noninvasive, convenient, and inexpensive and can provide information for health care professionals to identify T2DM patients who are at a high risk of albuminuria.

  18. Relationship Between Sarcopenia and Albuminuria: The 2011 Korea National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Kim, Tae Nyun; Lee, Eun Ju; Hong, Jae Won; Kim, Jung Min; Won, Jong Chul; Kim, Mi Kyung; Noh, Jung Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun

    2016-01-01

    Studies have shown that albuminuria, obesity, and sarcopenia may share pathophysiological processes related to cardiovascular disease risk. Their direct relationships, however, have not been examined. This study investigated the association between albuminuria and sarcopenia in a representative fraction of the Korean population.Of the 10,589 people who participated in the 2011 Korea National Health and Nutrition Examination Survey, 2158 participants aged over 19 years had been tested for albumin-to-creatinine ratio and for body composition data using dual-energy x-ray absorptiometry. Albuminuria was defined as an albumin-to-creatinine ratio ≥30 mg/g. Sarcopenia was defined as a skeletal muscle index (SMI) (SMI (%) = total appendicular skeletal muscle mass [kg]/weight [kg] × 100) of less than 1 standard deviation (SD) (grade 1) or 2 SD (grade 2) below the sex-specific mean for a younger reference group.The prevalence of albuminuria was higher in those with grade 2 sarcopenia than in those with a normal SMI or grade 1 sarcopenia (33.3% versus 8.4% and 8.9%; P sarcopenia was also more prevalent in participants with albuminuria than in those with the upper tertile of normoalbuminuria. In addition, multiple logistic regression analysis showed the odds ratio for albuminuria risk in the grade 2 sarcopenia group was 2.93 (95% confidence interval [CI], 1.46-5.88), compared with normal SMI after adjusting for potential confounding factors, including the presence of obesity, diabetes, and hypertension. Moreover, individuals with albuminuria had an odds ratio of 3.39 (95% [confidence interval], 1.38-8.37) for grade 2 sarcopenia compared with those in the lowest tertile of normoalbuminuria.This is the first study to demonstrate that individuals with sarcopenia exhibited increased risk of albuminuria and vice versa.

  19. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

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    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  20. ALBUMINURIA AND DIABETES MELLITUS TYPE 2: AN OBSERVATIONAL STUDY FROM BARABANKI, LUCKNOW

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    Vivek

    2015-04-01

    Full Text Available INTRODUCTION: India leads the world with largest number of diabetic subjects and this is expected to further rise in coming years. Diabetic nephropathy affects 20 - 30% of patients with diabetes. It presents in its earliest stage with low levels of albumin in the urine (m icro - albuminuria. The determination of micro - albuminuria in diabetes mellitus is important as it is the earliest indication of diabetic nephropathy. When left untreated, it will eventually lead to end stage renal disease (ESRD. OBJECTIVE: To detect the o nset of albuminuria among diabetic patients and the effect of hyperglycemia in causing this condition at an early stage. MATERIALS AND METHODS: One hundred clinically diagnosed cases of non - insulin dependent diabetes mellitus (NIDDM were selected for the study, from Feb - 2014 to May - 2014 (4 months. Criteria for the diagnosis of DM were of patients having fasting blood glucose levels more than 126 mg/dl. Micro - albuminuria is defined when urinary albumin excretion rate (UAER in 24 - hr urine or short time col lected urine during the day time is in the range of 30 - 300 mg/24 - hrs. If excretion is less than 20 μgm/min, the patient is considered to have normo - albuminuria, and if excretion is higher than 200 μgm/min, he is considered to have macro - albuminuria or clin ical proteinuria. The data for biochemical analysis are expressed as means ± S. E. M. OBSERVATION: In our study 35% of the total patients developed albuminuria, while 65% were free from it. 10% patients developed micro - albuminuria who was less than 50 yrs, while it was seen in 15% patients having age more than 50 yrs. Our study shows that only 5% patients developed macro - albuminuria. Glyc osyl ated haemoglobin and fasting plasma glucose was significantly raised among all these patients. Conclusion: Considerin g the tremendous increase in the number of diabetic patients in India and health budgets of our country, an early detection and good control

  1. Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

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    Cho, Eun Bin; Shin, Hee-Young; Park, Sang Eon; Chun, Phillip; Jang, Hye Ryoun; Yang, Jin-ju; Kim, Hee Jin; Kim, Yeo Jin; Jung, Na-Yeon; Lee, Jin San; Lee, Juyoun; Jang, Young Kyoung; Jang, Eun Young; Kang, Mira; Lee, Jong-Min; Kim, Changsoo; Min, Ju-Hong; Ryu, Seungho; Na, Duk L; Seo, Sang Won

    2016-01-01

    We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures. PMID:26878913

  2. Low-grade albuminuria in children with obstructive sleep apnea.

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    Varlami, Vasiliki; Malakasioti, Georgia; Alexopoulos, Emmanouel I; Theologi, Vasiliki; Theophanous, Eleni; Liakos, Nikolaos; Daskalopoulou, Euphemia; Gourgoulianis, Konstantinos; Kaditis, Athanasios G

    2013-06-01

    Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index  5 episodes∙h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea. PMID:23228180

  3. Global Longitudinal Strain Is Not Impaired in Type 1 Diabetes Patients Without Albuminuria

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Sogaard, Peter; Andersen, Henrik Ullits;

    2015-01-01

    OBJECTIVES: The purpose of this study was to investigate if systolic myocardial function is reduced in all patients with type 1 diabetes (T1DM) or only in patients with albuminuria. BACKGROUND: Heart failure is a common cause of mortality in T1DM, and a specific diabetic cardiomyopathy has been...... function assessed by GLS was reduced in T1DM compared with control subjects. This difference, however, was driven solely by decreased GLS in T1DM patients with albuminuria. T1DM patients with normoalbuminuria have systolic myocardial function similar to healthy control subjects. These findings do...... suggested. It is not known whether myocardial dysfunction is a feature of T1DM per se or primarily associated with diabetes with albuminuria. METHODS: This cross-sectional study compared 1,065 T1DM patients without known heart disease from the outpatient clinic at the Steno Diabetes Center with 198 healthy...

  4. Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease : results of the TEMPO 3:4 Trial

    NARCIS (Netherlands)

    Gansevoort, Ron T; Meijer, Esther; Chapman, Arlene B; Czerwiec, Frank S; Devuyst, Olivier; Grantham, Jared J; Higashihara, Eiji; Krasa, Holly B; Ouyang, John; Perrone, Ronald D; Torres, Vicente E

    2015-01-01

    BACKGROUND: The TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The

  5. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data

    NARCIS (Netherlands)

    Matsushita, K.; Coresh, J.; Sang, Y.; Chalmers, J.; Fox, C.; Guallar, E.; Jafar, T.; Jassal, S.K.; Landman, G.W.; Muntner, P.; Roderick, P.; Sairenchi, T.; Schottker, B.; Shankar, A.; Shlipak, M.; Tonelli, M.; Townend, J.; Zuilen, A. van; Yamagishi, K.; Yamashita, K.; Gansevoort, R.; Sarnak, M.; Warnock, D.G.; Woodward, M.; Arnlov, J.; Wetzels, J.F.M.

    2015-01-01

    BACKGROUND: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta

  6. Albuminuria, Proteinuria, and Novel Urine Biomarkers as Predictors of Long-term Allograft Outcomes in Kidney Transplant Recipients

    NARCIS (Netherlands)

    Nauta, Ferdau L.; Bakker, Stephan J. L.; van Oeveren, Wim; Navis, Gerjan; van der Heide, Jaap J. Homan; van Goor, Harry; de Jong, Paul E.; Gansevoort, Ron T.

    2011-01-01

    Background: Proteinuria is an established marker of decreased kidney function after kidney transplant. It recently has been suggested that albuminuria might be a more reliable marker. Although albuminuria often is regarded as a marker of glomerular damage, because chronic renal allograft damage is b

  7. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes : a collaborative meta-analysis of individual participant data

    NARCIS (Netherlands)

    Matsushita, Kunihiro; Coresh, Josef; Sang, Yingying; Chalmers, John; Fox, Caroline; Guallar, Eliseo; Jafar, Tazeen; Jassal, Simerjot K.; Landman, Gijs W. D.; Muntner, Paul; Roderick, Paul; Sairenchi, Toshimi; Schoettker, Ben; Shankar, Anoop; Shlipak, Michael; Tonelli, Marcello; Townend, Jonathan; van Zuilen, Arjan; Yamagishi, Kazumasa; Yamashita, Kentaro; Gansevoort, Ron; Sarnak, Mark; Warnock, David G.; Woodward, Mark; Arnlov, Johan; de Zeeuw, Dick

    2015-01-01

    Background The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-

  8. Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon

    International Nuclear Information System (INIS)

    Few data are available on the extent of albuminuria in diabetic populations in the Middle East generally and in Lebanon specifically. We conducted this study to determine the prevalence of albuminuria and its major risk factors in a cohort of diabetic patients in Lebanon. Patients and Diabetic patients followed in the outpatient department at the American University of Beirut Medical Center (AUBMC) were included in a prospective observational study. AUBMC is a tertiary referral center and the outpatient department typically handles patients of low socioeconomic status with advanced disease. Patients were classified according to their urinary albumin-to-creatinine ratio (ACR) as having normoalbuminuria (ACR<30 mg/g creatinine), microalbuminuria (ACR=30 to <300 mg/g creatinine), or macro-albuminuria (ACR 2300 mg/g creatinine). The three groups were compared to analyze the association between albuminuria and its risk factors. In addition, independent predictors of albuminuria were determined using multivariate logistic regression and presented as an odds ratio.Microalbuminuria and macroalbuminuria were present in 33.3% and 12.7% of 222 patients (mean age 56.4 years, mean deviation of diabetes 8.6 years, 58.7% women, 43.8% obese), respectively. Factors significantly associated with microalbuminuria included glycemic control, insulin use, and total and LDL cholesterol.Those associated with macroalbuminuria included in addition to glycemic control and insulin use, duration of diabetes, hypertension, elevated mean arterial pressure (MAP), and presence of neuropathy, retinopathy and peripheral vascular disease by bivariate analysis. Only glycemic control was an independent risk factor for both in addition to MAP and retinopathy for macroalbuminuria by multivariate analysis. Albuminuria is highly prevalent among this cohort of diabetic patients in Lebanon. Both glyce-mic control and blood pressure need to be better targeted in its management (Author).

  9. Albuminuria Assessed From First-Morning-Void Urine Samples Versus 24-Hour Urine Collections as a Predictor of Cardiovascular Morbidity and Mortality

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Brantsma, Auke H.; de Zeeuw, Dick; Bakker, Stephan J. L.; de Jong, Paul E.; Gansevoort, Ron T.

    2008-01-01

    Screening for albuminuria has been advocated because it is associated with cardiovascular morbidity and all-cause mortality. The "gold standard" to assess albuminuria is 24-hour urinary albumin excretion (UAE). Because 24-hour urine collection is cumbersome, guidelines suggest measuring albuminuria

  10. Towards a rational screening strategy for albuminuria: results from the unreferred renal insufficiency trial.

    Directory of Open Access Journals (Sweden)

    Arjan van der Tol

    Full Text Available BACKGROUND: There remains debate about the screening strategies for albuminuria. This study evaluated whether a screening strategy in an apparently healthy population based on basic clinical and biochemical parameters could be more effective than a strategy where screening for albuminuria is performed unselectively. METHODOLOGY/PRINCIPAL FINDINGS: The Unreferred Renal Insufficiency (URI Study is a cross-sectional study on the prevalence of metabolic risk factors in Belgian workers, volunteering to be screened during a routine yearly occupational check-up. Subjects (n = 295 with treated hypertension, known diabetes, treated dyslipidaemia, cardiovascular and renal disease were excluded. Among 1,191 apparently healthy subjects, 23% had unknown hypertension, 13% had impaired glucose tolerance, 15.4% had normoalbuminuria, 4.2% had microalbuminuria and 0.4% had macroalbuminuria. Subjects with resting heart rate ≥85 bpm, plasma glucose ≥5.6 mmol/L and blood pressure ≥140/90 mmHg were associated with albuminuria of any degree. A strategy where only subjects with at least one of these risk factors (n = 431 were screened for albuminuria, would identify all subjects with macroalbuminuria (5/5, 64% of those with microalbuminuria (32/50, and less than half of those with normoalbuminuria (81/183. An alternative strategy whereby subjects were first screened for presence of albuminuria, and additional cardiovascular risk factors were only measured in subjects positive for albuminuria (n = 238, would identify only 27% (118/431 of the subjects with additional and potentially modifiable cardiovascular risk factors. On the other hand, half of the subjects in this study with albuminuria (120/238, of which 102 had normoalbuminuria, had no additional cardiovascular risk factor at all. CONCLUSIONS: Screening an apparently healthy population directly for albuminuria will result in a high percentage of false positives, mostly measured in the normal

  11. Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy

    DEFF Research Database (Denmark)

    Kohan, Donald E; Lambers Heerspink, Hiddo J; Coll, Blai;

    2015-01-01

    ) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. RESULTS: Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP....... CONCLUSIONS: In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria...

  12. Serum Magnesium Concentration Is Inversely Associated with Albuminuria and Retinopathy among Patients with Diabetes

    Science.gov (United States)

    Lu, Jun; Gu, Yuying; Guo, Meixiang; Chen, Peihong; Wang, Hongtao

    2016-01-01

    Aim. To investigate the association between serum magnesium levels and microvascular complications among patients with diabetes. Methods. Patients with diabetes were recruited between April 2012 and January 2015. All patients received an assay of serum magnesium concentration, were screened for 24 h albumin excretion rate, and underwent nonmydriatic fundus photography. Albuminuria and retinopathy were defined accordingly. A total of 3,100 patients with normal serum magnesium levels were included in this study. Results. Patients with albuminuria and/or retinopathy had lower levels of serum magnesium than patients without these complications (P diabetic microvascular complications among patients with serum magnesium levels within the normal range.

  13. Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy

    NARCIS (Netherlands)

    Kohan, Donald E; Lambers Heerspink, Hiddo J; Coll, Blai; Andress, Dennis; Brennan, John J; Kitzman, Dalane W; Correa-Rotter, Ricardo; Makino, Hirofumi; Perkovic, Vlado; Hou, Fan Fan; Remuzzi, Giuseppe; Tobe, Sheldon W; Toto, Robert; Parving, Hans-Henrik; de Zeeuw, Dick

    2015-01-01

    BACKGROUND AND OBJECTIVES: Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced

  14. Baseline albuminuria predicts the efficacy of blood pressure-lowering drugs in preventing cardiovascular events

    NARCIS (Netherlands)

    Boersma, C.; Postma, M.J.; Visser, S.T.; Atthobari, J.; de Jong, P.E.; de Jong-van den Berg, L.T.; Gansevoort, R.T.

    2008-01-01

    AIMS Albuminuria has been proven to be associated with cardiovascular (CV) events in specific patient populations, but also in the general population. This study aimed to investigate whether the efficacy of blood pressure-lowering agents in preventing CV events depends on baseline urinary albumin ex

  15. Estimated GFR, Albuminuria, and Cognitive Performance : The Maastricht Study

    NARCIS (Netherlands)

    Martens, Remy J H; Kooman, Jeroen P; Stehouwer, Coen D A; Dagnelie, Pieter C; van der Kallen, Carla J H; Koster, Annemarie; Kroon, Abraham A; Leunissen, Karel M L; Nijpels, Giel; van der Sande, Frank M; Schaper, Nicolaas C; Sep, Simone J S; van Boxtel, Martin P J; Schram, Miranda T; Henry, Ronald M A

    2016-01-01

    BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. STUDY DESIGN: Cross

  16. [The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].

    Science.gov (United States)

    Fernández González, R; García Robles, R; Rodríguez Pérez, J C; Gómez Pajuelo, C; Moreno Carretero, E

    2001-01-01

    The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil

  17. Water-Pipe Smoking and Albuminuria: New Dog with Old Tricks

    Science.gov (United States)

    Ishtiaque, Iqra; Shafique, Kashif; Ul-Haq, Zia; Shaikh, Abdul Rauf; Khan, Naveed Ali; Memon, Abdul Rauf; Mirza, Saira Saeed; Ishtiaque, Afra

    2014-01-01

    Water-pipe (WP) smoking is on rise worldwide for the past few years, particularly among younger individuals. Growing evidence indicates that WP smoking is as harmful as cigarette smoking. To date, most of the research has focused on acute health effects of WP smoking, and evidence remains limited when it comes to chronic health effects in relation to long-term WP smoking. Therefore, the aim of this study was to examine the association between WP smoking and albuminuria in apparently healthy individuals. This analysis was conducted on data of a population-based cross-sectional study—the Urban Rural Chronic Diseases Study (URCDS). The study sample was recruited from three sites in Pakistan. Trained nurses carried out individual interviews and obtained the information on demographics, lifestyle factors, and past and current medical history. Measurements of complete blood count, lipid profile, fasting glucose level, and 24-hour albuminuria were also made by using blood and urine samples. Albumin excretion was classified into three categories using standard cut-offs: normal excretion, high-normal excretion and microalbuminuria. Multiple logistic regression models were used to examine the relationship between WP smoking and albuminuria. The final analysis included data from 1,626 health individuals, of which 829 (51.0%) were males and 797 (49.0%) females. Of 1,626 individuals, 267 (16.4%) were current WP smokers and 1,359 (83.6%) were non-WP smokers. WP smoking was significantly associated with high-normal albuminuria (OR  =  2.33, 95% CI 1.68-3.22, p-value <0.001) and microalbuminuria (OR  =  1.75, 95% CI 1.18-2.58, p-value 0.005) after adjustment for age, sex, BMI, social class, hypertension, and diabetes mellitus. WP smoking was significantly associated with high-normal albuminuria and microalbuminuria when analysis was stratified on hypertension and diabetes mellitus categories. WP smoking has a strong association with albuminuria in apparently healthy

  18. Water-pipe smoking and albuminuria: new dog with old tricks.

    Directory of Open Access Journals (Sweden)

    Iqra Ishtiaque

    Full Text Available Water-pipe (WP smoking is on rise worldwide for the past few years, particularly among younger individuals. Growing evidence indicates that WP smoking is as harmful as cigarette smoking. To date, most of the research has focused on acute health effects of WP smoking, and evidence remains limited when it comes to chronic health effects in relation to long-term WP smoking. Therefore, the aim of this study was to examine the association between WP smoking and albuminuria in apparently healthy individuals. This analysis was conducted on data of a population-based cross-sectional study--the Urban Rural Chronic Diseases Study (URCDS. The study sample was recruited from three sites in Pakistan. Trained nurses carried out individual interviews and obtained the information on demographics, lifestyle factors, and past and current medical history. Measurements of complete blood count, lipid profile, fasting glucose level, and 24-hour albuminuria were also made by using blood and urine samples. Albumin excretion was classified into three categories using standard cut-offs: normal excretion, high-normal excretion and microalbuminuria. Multiple logistic regression models were used to examine the relationship between WP smoking and albuminuria. The final analysis included data from 1,626 health individuals, of which 829 (51.0% were males and 797 (49.0% females. Of 1,626 individuals, 267 (16.4% were current WP smokers and 1,359 (83.6% were non-WP smokers. WP smoking was significantly associated with high-normal albuminuria (OR  =  2.33, 95% CI 1.68-3.22, p-value <0.001 and microalbuminuria (OR  =  1.75, 95% CI 1.18-2.58, p-value 0.005 after adjustment for age, sex, BMI, social class, hypertension, and diabetes mellitus. WP smoking was significantly associated with high-normal albuminuria and microalbuminuria when analysis was stratified on hypertension and diabetes mellitus categories. WP smoking has a strong association with albuminuria in apparently

  19. Influence of albuminuria and glomerular filtration rate on blood pressure response to antihypertensive drug therapy

    Directory of Open Access Journals (Sweden)

    John M Flack

    2008-01-01

    Full Text Available John M Flack1, Karl Duncan2, Suzanne E Ohmit3, Ruth Quah1, Xuefeng Liu1, Preeti Ramappa1, Sandra Norris1, Lowell Hedquist1, Amanda Dudley1, Samar A Nasser11Division of Translational Research and Clinical Epidemiology, Department of Internal Medicine, Wayne State University, Detroit, MI, USA; 2Department of Interventional Cardiology, Harper University Hospital, Detroit Medical Center, Detroit, MI, USA; 3School of Public Health, University of Michigan, Ann Arbor, MI, USABackground: Albuminuria and glomerular filtration rate (GFR, two factors linked to kidney and vascular function, may influence longitudinal blood pressure (BP responses to complex antihypertensive drug regimens.Methods: We reviewed the clinic records of 459 patients with hypertension in an urban, academic practice.Results: Mean patient age was 57-years, 89% of patients were African American, and 69% were women. Mean patient systolic/diastolic BP (SBP/DBP at baseline was 171/98 mmHg while taking an average of 3.3 antihypertensive medications. At baseline, 27% of patients had estimated (eGFR <60 ml/min/1.732, 28% had micro-albuminuria (30–300 mg/g and 16% had macro-albuminuria (300 mg/g. The average longitudinal BP decline over the observation period (mean 7.2 visits was 25/12 mmHg. In adjusted regression models, macro-albuminuria predicted a 10.3 mmHg lesser longitudinal SBP reduction (p < 0.001 and a 7.9 mmHg lesser longitudinal DBP reduction (p < 0.001; similarly eGFR <60 ml/min/1.732 predicted an 8.4 mmHg lesser longitudinal SBP reduction (p < 0.001 and a 4.5 lesser longitudinal DBP reduction (p < 0.001. Presence of either micro- or macro-albuminuria, or lower eGFR, also significantly delayed the time to attainment of goal BP.Conclusions: These data suggest that an attenuated decline in BP in drug-treated hypertensives, resulting in higher average BP levels over the long-term, may mediate a portion of the increased risk of cardiovascular-renal disease linked to elevated

  20. Association of relatives of hemodialysis patients with metabolic syndrome, albuminuria and Framingham Risk Score.

    Directory of Open Access Journals (Sweden)

    Jiun-Chi Huang

    Full Text Available BACKGROUND AND AIM: Metabolic syndrome (MetS, albuminuria, and the Framingham Risk Score (FRS are significant predictors for cardiovascular disease (CVD. However, the relationship and clinical significance of these CVD predictors in individuals with a family history of end-stage renal disease (ESRD are unclear. We investigated the association of relatives of hemodialysis (HD patients with MetS, albuminuria, and the FRS. METHODS: One hundred and sixty-six relatives of HD patients and 374 age- and sex- matched community controls were enrolled. MetS was defined using the Adult Treatment Panel III for Asians. Albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g. CVD risk was evaluated by the FRS. RESULTS: A significantly higher prevalence of MetS (19.9% vs. 12.5%, P = 0.026, albuminuria (12.7% vs. 5.1%, P = 0.002 and high FRS risk ≥ 10% of 10-year risk (15.7% vs. 8.5%, P = 0.013 was found in relatives of HD patients compared to their counterpart controls. In multivariate analysis, being relatives of HD patients (vs. controls was an independent determinant for MetS (odds ratio [OR], 1.785; 95% confidence interval [CI], 1.045 to 3.050, albuminuria (OR, 2.891; 95% CI, 1.431 to 5.841, and high FRS risk (OR, 1.863; 95% CI, 1.015 to 3.418. Higher low-density lipoprotein cholesterol (OR, 1.034; 95% CI, 1.017 to 1.052 and betel nut chewing (OR, 13.994; 95% CI, 3.384 to 57.871 were independent determinants for having a high FRS risk in relatives of HD patients. CONCLUSIONS: Being relatives of HD patients was independently associated with MetS, albuminuria and high FRS risk, suggesting family members of ESRD patients may have higher CVD risks through the interactions of renal risk factors. Proactive surveillance of these CVD predictors and preventive strategies should be targeted to this high-risk population.

  1. Determination of albuminuria in the urine of diabetics for prevention and control of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Köbberling, Johannes

    2005-11-01

    Full Text Available The issue: Diabetes has become the main cause of endstage renal disease. The costs for the treatment of diabetic patients with endstage renal disease have increased in the last years and have become a relevant economic topic of the health service. The first unspecific predictor of a diabetic nephropathy is an albuminuria. The screening for diabetic nephropathy uses microalbuminuria as a proof. Objectives: * What significance does the determination of albuminuria have on the precaution and course-control of the diabetic nephropathy? a in type 1 diabetic patients, b in type 2 diabetic patients * Which is an appropriate time to determine the albuminuria for the purpose of precaution and course-control of the diabetic nephropathy? a in type 1 diabetic patients, b in type 2 diabetic patients * Which method of testing is most effective concerning economic and medical aspects? Methods: Published literature from 1998 up to 2004 was identified by searching in the most important databases. Most of the guidelines were found by hand searching in the internet. Results: Of 2,792 citation titles and abstracts examined, 274 articles were retrieved for full-text review. Five metaanalyses and reviews, one review about clearing of guidelines (regarding 18 international guidelines and four guidelines met the inclusion criteria for screening for microalbuminuria and type 1 diabetes. Seven metaanalyses, one HTA report, one review about clearing of guidelines (regarding 17 international guidelines, and seven guidelines met the inclusion criteria for screening for microalbuminuria and type 2 diabetes.At the moment, the determination of albuminuria still has a great significance because it is recommended in most published literature and guidelines. The time to determine the albuminuria depends on the age of the patients and their type of diabetes. Type 2 diabetic patients should start the determination when the diabetes is diagnosed whereas the determination is

  2. Stratification of Ambulatory Blood Pressure Monitoring Findings by Cluster Analysis in Patients with Arterial Hypertension, Obesity and Albuminuria

    OpenAIRE

    Samoyavcheva S.V.; Shkarin Vl.V.

    2013-01-01

    The aim of the investigation was to study the characteristics of ambulatory blood pressure monitoring (ABPM) indices in the combination of arterial hypertension (AH) with obesity and albuminuria using cluster analysis. Material and Methods. The study involved 70 AH patients randomly chosen, aged from 23 to 71 years (mean age — 47.9 years). ABPM was performed before antihypertensive therapy administration. We estimated body mass index and albuminuria level. ABPM indices were stratified int...

  3. Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Reinhard, Henrik;

    2009-01-01

    throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS: Placebo geometric mean albuminuria was 258 mg/day (range 84-2,361), mean +/- SD 24-h blood pressure was 140/73 +/- 15/8 mm......-79), more than either monotherapy (P mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P mm...

  4. Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension

    DEFF Research Database (Denmark)

    Rasmussen, Jon B.; Nordin, Lovisa S.; Thomsen, Jakúp A.;

    2016-01-01

    The objective of this cross-sectional study was to investigate risk markers indicating the presence of albuminuria in patients with hypertension in rural sub-Saharan Africa (SSA). Urine albumin-creatinine ratio, glycated hemoglobin (HbA1c ), blood pressure, anthropometry, and other patient...... characteristics including medications were assessed. We identified 160 patients with hypertension, of whom 68 (42.5%) were co-diagnosed with diabetes mellitus (DM). Among the included participants, 57 (35.6%) had albuminuria (microalbuminuria [n=43] and macroalbuminuria [n=14]). A backward multivariate logistic...... regression model identified age (per 10-year increment) (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.03-1.95), HbA1c >53 compared with treatment with dihydropyridine calcium channel blockers (OR, 2.59; 95% CI, 1.09-6.16) as the variables...

  5. Cost-effectiveness of aliskiren in type 2 diabetes, hypertension, and albuminuria

    DEFF Research Database (Denmark)

    Delea, Thomas E; Sofrygin, Oleg; Palmer, James L;

    2009-01-01

    The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type...... 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID...... on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime...

  6. Association of high blood pressure with renal insufficiency: role of albuminuria, from NHANES, 1999-2006.

    Directory of Open Access Journals (Sweden)

    Ping Yan

    Full Text Available BACKGROUND: The relationship between hypertension and kidney disease is complicated. Clinical trials found intense blood pressure control was not associated with alterations in glomerular filtration rate (GFR in all patients but did slow the rate of GFR decline among those with a higher baseline proteinuria. However, the underlying mechanism has been unclear. METHODS: We tested the hypothesis that the association between high blood pressure and renal function is modified by albuminuria status by conducting analyses in a cross-sectional study with 12,440 adult participants without known kidney diseases, diabetes or cardiovascular diseases, participating in the National Health and Nutrition Examination Survey (NHANES 1999-2006. RESULTS: 1226 out of 12440 were found to have unknown high blood pressure and 4494 were found to have reduced renal function. Overall, a moderate association was found between high blood pressure and renal function insufficiency in all participants analyzed. However, among participants with albuminuria, the prevalence of moderate-severe renal insufficiency substantially and progressively increased from normal subjects to prehypertensive and undiagnosed hypertensive subjects (1.43%, 3.44%, 10.96%, respectively, P for trend<0.0001; on the other hand, the prevalence of undiagnosed hypertension was also significantly higher among subjects with moderate-severe renal insufficiency than those with mild renal insufficiency (35.54% Vs 19.09%, P value <0.05, supporting an association between hypertension and renal function damage. In contrast, no association between hypertension and renal insufficiency was observed among those without albuminuria in this population. Similar findings were observed when the CKD-EPI equation was used. CONCLUSIONS: The association between high blood pressure and reduced renal function could be dependent upon the albuminuria status. This finding may provide a possible explanation for results observed in

  7. Effect of sensor-augmented pump treatment vs. multiple daily injections on albuminuria

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Willum Hansen, Tine; Rossing, Peter;

    2015-01-01

    CONTEXT: The effect of glycaemic control on persisting albuminuria remains unclear. Insulin delivery and glucose variability may be important Objective: To investigate the effect of 1 year treatment with sensor-augmented insulin pump (SAP) or multiple daily injections (MDI) on albuminuria. DESIGN......: Randomized controlled open-label parallel trial. PATIENTS AND METHODS: 60 type 1 diabetes patients, with a history of albuminuria and on stable RAS-inhibition, were randomized to SAP or MDI. Urine albumin creatinine ratio (UACR) was measured in 3 urine samples at all visits. Glucose variability......±12 years, UACR (geometric mean,IQR): 99(37-233) mg/g, (51)Cr-EDTA-GFR: 94±22 ml/min/1.73m(2), HbA1c: 9.0±1.1%, glucose variability (calculated as SD): 4.0±1.0 mmol/l; no groups differences (P≥0.06 for all). After 1 year, change in UACR was (mean(95%CI)) -13(-39-22) with SAP vs. 30(-12-92)% on MDI treatment...

  8. Plasma Molecular Signatures in Hypertensive Patients With Renin-Angiotensin System Suppression: New Predictors of Renal Damage and De Novo Albuminuria Indicators.

    Science.gov (United States)

    Baldan-Martin, Montserrat; Mourino-Alvarez, Laura; Gonzalez-Calero, Laura; Moreno-Luna, Rafael; Sastre-Oliva, Tamara; Ruiz-Hurtado, Gema; Segura, Julian; Lopez, Juan Antonio; Vazquez, Jesus; Vivanco, Fernando; Alvarez-Llamas, Gloria; Ruilope, Luis M; de la Cuesta, Fernando; Barderas, Maria G

    2016-07-01

    Albuminuria is a risk factor strongly associated with cardiovascular disease, the first cause of death in the general population. It is well established that renin-angiotensin system suppressors prevent the development of new-onset albuminuria in naïf hypertensive patients and diminish its excretion, but we cannot forget the percentage of hypertensive patients who develop de novo albuminuria. Here, we applied multiple proteomic strategy with the purpose to elucidate specific molecular pathways involved in the pathogenesis and provide predictors and chronic organ damage indicators. Briefly, 1143 patients were followed up for a minimum period of 3 years. One hundred and twenty-nine hypertensive patients chronically renin-angiotensin system suppressed were recruited, classified in 3 different groups depending on their albuminuria levels (normoalbuminuria, de novo albuminuria, and sustained albuminuria), and investigated by multiple proteomic strategies. Our strategy allowed us to perform one of the deepest plasma proteomic analysis to date, which has shown 2 proteomic signatures: (1) with predictive value of de novo albuminuria and (2) sustained albuminuria indicator proteins. These proteins are involved in inflammation, immune as well as in the proteasome activation occurring in situations of endoplasmic reticulum stress. Furthermore, these results open the possibility of a future strategy based on anti-immune therapy to treat hypertension which could help to prevent the development of albuminuria and, hence, the progression of kidney damage.

  9. Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei-Yueh; Chen, Szu-Chia; Shin, Shyi-Jang; Hsiao, Pi-Jung; Lin, Kun-Der; Hsu, Wei-Hao

    2016-01-01

    Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM. PMID:27490538

  10. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

    Science.gov (United States)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-03-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  11. Atrasentan Reduces Albuminuria by Restoring the Glomerular Endothelial Glycocalyx Barrier in Diabetic Nephropathy.

    Science.gov (United States)

    Boels, Margien G S; Avramut, M Cristina; Koudijs, Angela; Dane, Martijn J C; Lee, Dae Hyun; van der Vlag, Johan; Koster, Abraham J; van Zonneveld, Anton Jan; van Faassen, Ernst; Gröne, Hermann-Josef; van den Berg, Bernard M; Rabelink, Ton J

    2016-08-01

    Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial glycocalyx in diabetic apolipoprotein E (apoE)-deficient mice in relation to its antialbuminuric effects. Treatment with atrasentan (7.5 mg/kg/day) for 4 weeks reduced urinary albumin-to-creatinine ratios by 26.0 ± 6.5% (P < 0.01) in apoE knockout (KO) mice with streptozotocin-induced diabetes consuming an atherogenic diet, without changes in gross glomerular morphology, systemic blood pressure, and blood glucose concentration. Endothelial cationic ferritin surface coverage, investigated using large-scale digital transmission electron microscopy, revealed that atrasentan treatment increases glycocalyx coverage in diabetic apoE KO mice from 40.7 ± 3.2% to 81.0 ± 12.5% (P < 0.05). This restoration is accompanied by increased renal nitric oxide concentrations, reduced expression of glomerular heparanase, and a marked shift in the balance of M1 and M2 glomerular macrophages. In vitro experiments with endothelial cells exposed to laminar flow and cocultured with pericytes confirmed that atrasentan reduced endothelial heparanase expression and increased glycocalyx thickness in the presence of a diabetic milieu. Together these data point toward a role for the restoration of endothelial function and tissue homeostasis through the antialbuminuric effects of atrasentan, and they provide a mechanistic explanation for the clinical observations of reduced albuminuria with atrasentan in diabetic nephropathy.

  12. Inhibition of the soluble epoxide hydrolase promotes albuminuria in mice with progressive renal disease.

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    Oliver Jung

    Full Text Available Epoxyeicotrienoic acids (EETs are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH and sEH inhibitors are considered treatment for chronic renal failure (CRF. We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg, the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.

  13. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts : a collaborative meta-analysis

    NARCIS (Netherlands)

    Matsushita, Kunihiro; van der Velde, Marije; Astor, Brad C.; Woodward, Mark; Levey, Andrew S.; de Jong, Paul E.; Coresh, Josef; Gansevoort, Ron T.

    2010-01-01

    Background Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. Methods

  14. TLR-mediated albuminuria needs TNFα-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice

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    Nidhi Jain

    2016-06-01

    Full Text Available Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs in mice through engagement of Toll-like receptors (TLRs is widely studied as a partial model for some forms of human nephrotic syndrome (NS. In addition to TLRs, CD80 has been shown to be essential for PAMP-mediated albuminuria. However, the mechanistic relationships between TLRs, CD80 and albuminuria remain unclear. Here, we show that albuminuria and CD80-uria induced in mice by many TLR ligands are dependent on the expression of TLRs and their downstream signalling intermediate MyD88 exclusively in hematopoietic cells and, conversely, on CD80 expression exclusively in non-hematopoietic cells. TNFα is crucial for TLR-mediated albuminuria and CD80-uria, and induces CD80 expression in cultured renal podocytes. IL-10 from hematopoietic cells ameliorates TNFα production, albuminuria and CD80-uria but does not prevent TNFα-mediated induction of podocyte CD80 expression. Chitohexaose, a small molecule originally of parasite origin, mediates TLR4-dependent anti-inflammatory responses, and blocks TLR-mediated albuminuria and CD80-uria through IL-10. Thus, TNFα is a prominent mediator of renal CD80 induction and resultant albuminuria in this model, and small molecules modulating TLR-mediated inflammatory activation might have contributory or adjunct therapeutic potential in some contexts of NS development.

  15. Stratification of Ambulatory Blood Pressure Monitoring Findings by Cluster Analysis in Patients with Arterial Hypertension, Obesity and Albuminuria

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    Samoyavcheva S.V.

    2013-12-01

    Full Text Available The aim of the investigation was to study the characteristics of ambulatory blood pressure monitoring (ABPM indices in the combination of arterial hypertension (AH with obesity and albuminuria using cluster analysis. Material and Methods. The study involved 70 AH patients randomly chosen, aged from 23 to 71 years (mean age — 47.9 years. ABPM was performed before antihypertensive therapy administration. We estimated body mass index and albuminuria level. ABPM indices were stratified into clusters. Results. Clusters with normal heart rate prevailed in patients with normal weight and overweight, I degree obesity in all AH varuants. Hypertensive clusters with tachycardia were found to prevail in patients with II–III degree obesity. AH structure changed with body mass increase. In overweight and I degree obesity there grows the occurrence of systolic-diastolic AH clusters. In II–III degree obesity the clusters of systolic-diastolic and isolated diastolic AH were revealed less frequently than in normal body weight, while isolated systolic AH clusters were found more frequently. Their occurrence increased in patients with a high albuminuria level as well. Conclusion. ABPM data can be grouped into clusters, and their own pathogenic mechanisms of AH maintenance and regulation seem to prevail in each cluster. In overweight and I degree obesity patients the occurrence of systolic-diastolic AH increases. With obesity degree increase there is the tendency for heart rate rise, and hemodynamic AH variants are redistributed towards the increase of isolated systolic AH, which is likely to be due to the increase in AH severity with vascular wall remodeling progression. Isolated systolic AH prevalence is increasing not only in II–III degree obesity, but also in high albuminuria supporting the significance of systolic AH in albuminuria development. No interaction between albuminuria and heart rate was revealed.

  16. Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension.

    Science.gov (United States)

    Bakri, Mahinur; Yi, Yang; Chen, Ling-Dan; Aisa, Haji Akber; Wang, Mong-Heng

    2014-04-01

    In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers. PMID:24863351

  17. Clinical Observation on Breviscapine in Treating Hypertension Patients Complicated with Micro-albuminuria of Renal Impairment

    Institute of Scientific and Technical Information of China (English)

    WEI Ling; TAN Jie

    2005-01-01

    Objective:To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary β2-microglobulin (β2-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment. Results: In the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly (P<0.05), while in the treated group, both urinary β2-MG and quantitative determination of 24 hrs urinary protein got lowered significantly (P<0.05 and P<0.01). But after treatment, compared with the control group, urinary β2-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced (P<0.05). Conclusion: Besides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.

  18. Associations among systemic blood pressure, microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism

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    Hsiang Tsai-Yuan

    2010-11-01

    Full Text Available Abstract Background Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC. Methods This study investigated the relationships among adrenocorticotropic hormone (ACTH-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100, in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40, or adrenal-dependent hyperadrenocorticism (ADH; n = 30. Results Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803. However the incidence of hypertension was highest in dogs with ADH (p = 0.017, followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019. Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p p = 0.306. Conclusions Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.

  19. Elevated albuminuria associated with increased risk of recurrent venous thromboembolism : results of a population-based cohort study

    NARCIS (Netherlands)

    van Schouwenburg, Inge M.; Mahmoodi, Bakhtawar K.; Veeger, Nic J. G. M.; Kluin-Nelemans, Hanneke C.; Gansevoort, Ron T.; Meijer, Karina

    2012-01-01

    This study examined the risk of recurrent venous thromboembolism (VTE) in patients with elevated albuminuria. In 1997-1998, inhabitants of Groningen, the Netherlands, aged 28-75 years (n = 85 421), were invited to participate in the PREVEND(Prevention of REnal and Vascular ENd stage Disease) Study,

  20. A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury

    NARCIS (Netherlands)

    Grams, Morgan E.; Sang, Yingying; Ballew, Shoshana H.; Gansevoort, Ron T.; Kimm, Heejin; Kovesdy, Csaba P.; Naimark, David; Oien, Cecilia; Smith, David H.; Coresh, Josef; Sarnak, Mark J.; Stengel, Benedicte; Tonelli, Marcello; de Zeeuw, Dick; Bakker, Stephan J. L.; van der Harst, Pim; Heerspink, Hiddo J.; Hillege, Hans L.

    2015-01-01

    Background: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). Study Design: Collaborativ

  1. Albuminuria Is Associated with Traditional Cardiovascular Risk Factors and Viral Load in HIV-Infected Patients in Rural South Africa.

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    G Emerens Wensink

    Full Text Available As life expectancy improves among Human Immunodeficiency Virus (HIV patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions between HIV, cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV.In a rural primary health care centre, 903 HIV-infected adult patients were randomly selected and data on HIV-infection and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g. Multivariate logistic regression analysis was used to analyse albuminuria and demographic, clinical and HIV-associated variables.The study population consisted of 903 HIV-infected patients, with a median age of 40 years (Inter-Quartile Range (IQR 34-48 years, and included 625 (69% women. The median duration since HIV diagnosis was 26 months (IQR 12-58 months and 787 (87% received antiretroviral therapy. Thirty-six (4% of the subjects were shown to have diabetes and 205 (23% hypertension. In the cohort, 21% had albuminuria and 2% an eGFR <60 mL/min/1.73m2. Albuminuria was associated with hypertension (adjusted odds ratio (aOR 1.59; 95% confidence interval (CI 1.05-2.41; p<0.05, total cholesterol (aOR 1.31; 95% CI 1.11-1.54; p<0.05, eGFR (aOR 0.98; 95% CI 0.97-0.99; p<0.001 and detectable viral load (aOR 2.74; 95% CI 1.56-4.79; p<0.001. Hypertension was undertreated: 78% were not receiving treatment, while another 11% were inadequately treated. No patients were receiving lipid-lowering medication.Glomerular filtration rate was well conserved, while albuminuria was common amongst HIV-infected patients in rural South Africa. Both cardiovascular and HIV-specific variables were associated with albuminuria. Improved cardiovascular risk prevention as well as adequate

  2. Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

    Science.gov (United States)

    Kitagawa, Noriyuki; Okada, Hiroshi; Tanaka, Muhei; Hashimoto, Yoshitaka; Kimura, Toshihiro; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

    2016-08-01

    The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30 mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross-sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, Pperipheral SBP (odds ratio, 1.029; 95% confidence interval, 1.016-1.043) or central SBP (odds ratio, 1.022; 95% confidence interval, 1.011-1.034) was associated with an increased odds of albuminuria. In addition, AUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes.

  3. Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats.

    Science.gov (United States)

    Jenkin, Kayte A; O'Keefe, Lannie; Simcocks, Anna C; Grinfeld, Esther; Mathai, Michael L; McAinch, Andrew J; Hryciw, Deanne H

    2015-05-01

    Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague-Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9). In a different cohort, rats were fed a HFD for 15 weeks. After 9 weeks consuming a HFD, rats were injected daily for 6 weeks with 3 mg/kg AM251 (n=9) or saline via i.p. injection (n=9). After 10 weeks consuming a HFD, CB1 and megalin protein expression were significantly increased in the kidneys of obese rats. Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats. Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinaemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGFA, TGFB1 and collagen IV in the kidney. This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats. PMID:25804605

  4. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy : a randomised trial

    NARCIS (Netherlands)

    de Zeeuw, Dick; Bekker, Pirow; Henkel, Elena; Hasslacher, Christopher; Gouni-Berthold, Ioanna; Mehling, Heidrun; Potarca, Antonia; Tesar, Vladimir; Lambers Heerspink, Hiddo J.; Schall, Thomas J.

    2015-01-01

    Background Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX

  5. Diabetic Albuminuria Is Due to a Small Fraction of Nephrons Distinguished by Albumin-Stained Tubules and Glomerular Adhesions

    OpenAIRE

    Kralik, Patricia M.; Long, Yunshi; Song, Ye; Yang, Lu; Wei, Haiyang; Coventry, Susan; Zheng, Shirong; Epstein, Paul N.

    2009-01-01

    OVE26 diabetic mice develop severe albuminuria. Immunohistochemical analysis revealed a pattern of intense albumin staining in a small subset of OVE26 tubules. Immunostaining was strikingly heterogeneous; some tubules stained intensely for albumin, but most tubules had weak or no staining. Serial sectioning showed that staining patterns were distinctive for each nephron. Electron microscopy revealed that albumin accumulated in villi and at the base of the brush border. Tubule cell injury, as ...

  6. The usefulness of a free self-test for screening albuminuria in the general population: a cross-sectional survey

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    Schellevis François G

    2009-10-01

    Full Text Available Abstract Background In this study we evaluated the usefulness of a free self-test for screening albuminuria in the general population. Methods Dutch adults were invited by the Dutch Kidney Foundation to order a free albuminuria self-test, consisting of three semi quantitative dipstick tests, via the Internet. Results were classified in negative, low-positive and high-positive. In case of a positive test result, the tester was recommended to visit a GP for supplementary examination and/or treatment. Participants of the programme were sent a questionnaire for evaluation by e-mail eight weeks after receiving the self-test. Results During the first 30 days of the self-test programme, 996,927 self-tests were ordered. In total, 71,714 participants completed the questionnaire: 79% had a negative test result and 21% had a positive test result (20% low-positive and 1% high-positive. Of the positive testers, 25% visited a GP after testing for albuminuria. Among the 3,983 participants who visited a GP, 193 new diseases were detected: 25 chronic renal failure, 152 hypertension and 31 diabetes mellitus. Conclusion Using a free self-test for screening albuminuria in the general population resulted in a large response and a number of newly detected diseases. However, we found a very high percentage of positive testers of which probably a large part is false positive. Furthermore, only a small part of the positive testers visited a GP for additional examination and/or treatment. The efficiency of such a campaign could be increased by embedding the testing in health care to reduce the number of false-positive results and to ensure follow-up and treatment in case of a positive test result.

  7. Albuminuria is Associated With Subendocardial Viability Ratio in Chronic Kidney Disease Patients

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    Robert Ekart

    2015-10-01

    Full Text Available Background/Aims: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA employs the technique of applanation tonometry to obtain a peripheral pulse pressure waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR and ejection duration (ED. SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD patients. Methods: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1% were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP monitoring were performed. The following parameters were calculated: (1 aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75, (2 SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3 ED, (4 estimated central aortic systolic and diastolic pressure and (5 central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR were analyzed; UACR values were natural log transformed (lnUACR. Results: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73m2 (mean 32.6; SD±24.6. We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004, eGFR (r=-0.219; P=0.04, hemoglobin (r=-0.255; P=0.02, phosphorus (r=0.222; P=0.04, iPTH (r=0.268; P=0.01, SEVR (r=-0.254; P=0.02 and ED (r=0.315; P=0.003. No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic

  8. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial.

    Science.gov (United States)

    Borges, Cynthia M; Papadimitriou, Alexandros; Duarte, Diego A; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect. PMID:27320846

  9. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial.

    Science.gov (United States)

    Borges, Cynthia M; Papadimitriou, Alexandros; Duarte, Diego A; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect.

  10. Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.

    Science.gov (United States)

    Miles, Clifford D; Skorupa, Jill Y; Sandoz, John P; Rigley, Theodore H; Nielsen, Kathleen J; Stevens, R Brian

    2011-01-01

    Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications. PMID:21077952

  11. Alpha thalassemia protects sickle cell anemia patients from macro-albuminuria through its effects on red blood cell rheological properties.

    Science.gov (United States)

    Lamarre, Yann; Romana, Marc; Lemonne, Nathalie; Hardy-Dessources, Marie-Dominique; Tarer, Vanessa; Mougenel, Danielle; Waltz, Xavier; Tressières, Benoît; Lalanne-Mistrih, Marie-Laure; Etienne-Julan, Maryse; Connes, Philippe

    2014-01-01

    While chronic hemolysis has been suspected to be involved in the development of glomerulopathy in patients with sickle cell anemia (SCA), no study focused on the implications of blood rheology. Ninety-six adults with SCA at steady state were included in the present cross-sectional study. Three categories were defined: normo-albuminuria (NORMO, n = 41), micro-albuminuria (MICRO, n = 23) and macro-albuminuria (MACRO, n = 32). Blood was sampled to measure hematological and hemorheological parameters, and genomic DNA extraction was performed to detect the presence of α-thalassemia. The prevalence of α-thalassemia was lower in the MACRO group compared with the two other groups. Anemia was more severe in the MACRO compared with the NORMO group leading the former group to exhibit decreased blood viscosity. Red blood cell deformability was lower and red blood cell aggregates strength was greater in the MACRO compared to the two other groups, and this was directly attributed to the lower frequency of α-thalassemia in the former group. Our results show the protective role of α-thalassemia against the development of sickle cell glomerulopathy, and strongly suggest that this protection is mediated through the decrease of anemia, the increase of RBC deformability and the lowering of the RBC aggregates strength.

  12. Sugary soda consumption and albuminuria: results from the National Health and Nutrition Examination Survey, 1999-2004.

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    David A Shoham

    Full Text Available BACKGROUND: End-stage renal disease rates rose following widespread introduction of high fructose corn syrup in the American diet, supporting speculation that fructose harms the kidney. Sugar-sweetened soda is a primary source of fructose. We therefore hypothesized that sugary soda consumption was associated with albuminuria, a sensitive marker for kidney disease. METHODOLOGY/PRINCIPAL FINDINGS: Design was a cross-sectional analysis. Data were drawn from the National Health and Nutrition Examination Survey (NHANES, 1999-2004. The setting was a representative United States population sample. Participants included adults 20 years and older with no history of diabetes mellitus (n = 12,601; after exclusions for missing outcome and covariate information (n = 3,243, the analysis dataset consisted of 9,358 subjects. Exposure was consumption of two or more sugary soft drinks, based on 24-hour dietary recall. The main outcome measure was Albuminuria, defined by albumin to creatinine ratio cutpoints of >17 mg/g (males and >25 mg/g (females. Logistic regression adjusted for confounders (diet soda, age, race-ethnicity, gender, poverty. Interactions between age, race-ethnicity, gender, and overweight-obesity were explored. Further analysis adjusted for potential mediators: energy intake, basal metabolic rate, obesity, hypertension, lipids, serum uric acid, smoking, energy expenditure, and glycohemoglobin. Alternative soda intake definitions and cola consumption were employed. RESULTS: Weighted albuminuria prevalence was 11%, and 17% consumed 2+ sugary soft drinks/day. The confounder-adjusted odds ratio for sugary soda was 1.40 (95% confidence interval: 1.13, 1.74. Associations were modified by gender (p = 0.008 and overweight-obesity (p = 0.014. Among women, the OR was 1.86 (95% CI: 1.37, 2.53; the OR among males was not significant. In the group with body mass under 25 kg/m(2, OR = 2.15 (95% confidence interval: 1.42, 3.25. Adjustment for potential

  13. Albuminuria and its correlates in an Iranian type 2 diabetic population

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    Meysamie Alipasha

    2008-08-01

    Full Text Available Abstract Objective To study the prevalence and correlates of increased urinary albumin excretion (UAE in an Iranian type 2 diabetic population. Methods Over a one year period since October 2002, 400 consecutive type 2 diabetic patients referred to an outpatient diabetes clinic, were enrolled in a cross sectional study. Subjects had no history of renal impairment or overt proteinuria. Data concerning demographic characteristics and cardiovascular risk factors were recorded and height, weight and blood pressure were measured. Glucose, cholesterol, HDL-C, LDL-C, triglyceride, apoprotein B, lipoprotein a, creatinine, and HbA1c were measured in fasting blood samples. Overnight twelve-hour UAE were assessed by immunoturbidometry method. Regression analyses were employed to determine the correlates of UAE. Results Out of 400 patients, 156 (40% subjects had increased UAE (UAE ≥ 30 mg/24 hour. The UAE was higher in males compared to females (145.5 vs. 72.1 mg/day; p Conclusion In this study, increased UAE was considerably frequent among type 2 diabetic patients without any significant history of renal dysfunction. Albuminuria was found to be associated with dyslipidemia (low HDL-C, long duration of diabetes, and uncontrolled glycemia revealed by higher HbA1c.

  14. Association of the estimated 24-h urinary sodium excretion with albuminuria in adult koreans: the 2011 Korea National Health and Nutrition Examination Survey.

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    Sang Youb Han

    Full Text Available BACKGROUND: Sodium intake and albuminuria have important roles in blood pressure and renal progression. Although their relationship has been reported, the results have not been consistent and all studies have examined small populations. OBJECTIVE: This study investigated the role of the estimated 24-h urinary sodium excretion as a marker of sodium intake and albuminuria. DESIGN: This investigation included 5,187 individuals age 19 years and older from a cross-sectional, nationally representative, stratified survey: The Korea National Health and Nutrition Examination Survey (KNHANES V-2, in 2011. Albuminuria was defined as a urinary albumin/creatinine ratio ≥30 mg/g. The 24-h urinary sodium excretion was estimated from a spot urine. RESULTS: On classifying our participants into quartiles based on the estimated 24-h urinary sodium excretion, the prevalence of albuminuria increased with the 24-h urinary sodium excretion (5.3, 5.7, 7.5, and 11.8% in the first through fourth quartiles, respectively, p for trend <0.001. Even after adjusting for age, sex, diabetes, obesity, and hypertension, the significance persisted. In a multiple logistic regression analysis, the second and third quartiles of the estimated 24-h urinary sodium excretion were not associated with the presence of albuminuria with the first quartile as a control. However, the fourth quartile was significantly associated with the presence of albuminuria (odds ratio 1.61 [95% confidence interval 1.71-2.21], p = 0.003 after adjusting for age, sex, diabetes, obesity, and hypertension. CONCLUSIONS: These findings suggest that salt intake is associated with the presence of albuminuria in the general Korean adult population.

  15. Amlodipine Reduces Inflammation despite Promoting Albuminuria in the Streptozotocin-Induced Diabetic Rat

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    Elizabeth R. Flynn

    2012-07-01

    Full Text Available Amlodipine reduces blood pressure; however, its effect in the diabetic kidney irrespective of its blood pressure-lowering effects is unclear. This study examined the effects of amlodipine (0, 5, 10 and 20 mg/kg; DA0, DA5, DA10 and DA20, respectively for 12 weeks on renal functional and structural changes in the streptozotocin-induced diabetic rat, a nonhypertensive model of diabetes-associated hyperfiltration. Compared with nondiabetic rats, diabetes (D was associated with increased urine albumin excretion (UAE, 12.6 ± 3.40 vs. 3.73 ± 1.14 mg/day, glomerular filtration rate (2.17 ± 0.09 vs. 1.64 ± 0.12 ml/min/g kidney weight, glomerulosclerosis (0.21 ± 0.03 vs. 0.05 ± 0.01 AU and infiltration of inflammatory cells (18.5 ± 2.78 vs. 6.92 ± 0.70 cells/cm2, but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg. While DA20 abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight and inflammatory cell abundance (6.0 ± 0.79 cells/cm2, it exacerbated UAE (43.5 ± 8.49 mg/day and increased MAP (132 ± 3.76 mm Hg, but had no effect on renal pathology. These data suggest that amlodipine reduces renal inflammation and abolished glomerular hyperfiltration, but increases blood pressure and exacerbates albuminuria in the rat model of normotensive diabetic kidney disease. We conclude that amlodipine may have limited renoprotective effects in the face of hyperfiltration and absence of elevated blood pressure.

  16. A study of the relationship between albuminuria, proteinuria and urinary reagent strips.

    LENUS (Irish Health Repository)

    Collier, Geraldine

    2012-02-01

    BACKGROUND: The aims of this study were to examine the relationship between proteinuria and albuminuria and to assess the equivalence between the albumin to creatinine ratio (ACR) and the protein to creatinine ratio (PCR) at the cut-offs recommended by the National Institute for Health and Clinical Excellence (NICE) guidance on chronic kidney disease. The sensitivity and specificity of the reagent strips used in our laboratory for the detection of clinical proteinuria was also assessed. METHODS: Urine samples (n = 117) were screened for protein using the Bayer Multistix 10SG and read manually. Urinary total protein and creatinine was measured on the Roche P Modular by the benzethonium chloride and kinetic Jaffe methods, respectively. Urinary albumin was measured by immunoturbidimetry on the Roche Cobas Mira. RESULTS: The relationship between urinary protein and albumin loss was non-linear (P < 0.05). As urinary protein loss increased the percentage of albumin to total protein increased. At the NICE guidance recommended cut-offs for clinical proteinuria (ACR > or =30 mg\\/mmol and PCR > or =50 mg\\/mmol) there was one discordant result between ACR and PCR (ACR <30 mg\\/mmol and PCR >50 mg\\/mmol). The Bayer Multistix 10SG had a sensitivity and specificity of 97% and 62%, respectively, for the detection of clinical proteinuria compared with ACR. CONCLUSIONS: The proportion of urinary total protein attributable to albumin changes with concentration. There was only one discordant result between ACR and PCR: therefore either ratio may be used for the identification of clinical proteinuria. As a screening test for proteinuria, the Bayer Multistix 10SG had an acceptable sensitivity but poor specificity.

  17. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

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    J. Škrha

    2013-01-01

    Full Text Available The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE in patients with diabetes. Skin autofluorescence (AF assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/ and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P<0.0001. Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r=0.37, P<0.02 and r=0.60, P<0.0001, but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2=0.38. Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  18. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  19. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    Science.gov (United States)

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established. PMID:23671885

  20. Significance of anti-nuclear and anti-extracellular matrix autoantibodies for albuminuria in murine lupus nephritis : a longitudinal study on plasma and glomerular eluates in MRL/1 mice

    NARCIS (Netherlands)

    VanBruggen, MCJ; Kramers, C; Hylkema, MN; Smeenk, RJT; Berden, JHM

    1996-01-01

    The relationship between autoantibody reactivities and nephritis in systemic lupus erythematosus (SLE) is unclear. We studied MRL/1 mice which developed a considerable albuminuria (either mice with short (<1 week) or heavy and prolonged (3 weeks) albuminuria) and compared them with non-albuminuric a

  1. Hyperuricemia is an independent risk factor for new onset micro-albuminuria in a middle-aged and elderly population: a prospective cohort study in taiwan.

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    Hung-Yu Chang

    Full Text Available BACKGROUND: Hyperuricemia is now regarded as a risk factor for cardiovascular disease. Micro-albuminuria is associated with increased risk for cardiovascular disease and chronic kidney disease. We hypothesized that elevated serum uric acid (UA is associated with development of micro-albuminuria in the general population. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community-based prospective cohort study. A total of 1862 subjects from southern Taiwan, all older than 40 years, were screened and 993 of these participants without micro-albuminuria were followed for 4 years. Urinary albumin-to-creatinine ratio was measured two times per year. A multiple linear regression model indicated that serum UA was independently associated with ln(ACR after adjustment for 8 factors (age, sex, and 6 metabolic metrics (β = 0.194, p<0.01. Logistic regression analysis indicated that each 1 mg/dL increase of UA was associated with a 1.42-fold increased risk of micro-albuminuria after adjustment for the same 8 factors (OR = 1.42, 95% CI: 1.27-1.59, p<0.01. A Cox regression model using subjects with serum UA less than 5 mg/dL as reference group indicated higher hazard ratios (HRs only found in subjects with serum UA more than 7 mg/dL (HR = 3.54, 95% CI: 2.11-5.93, p<0.01 and not in subjects with serum UA of 5 to 7 mg/dL (HR = 1.30, 95% CI: 0.82-2.07, p = 0.15. CONCLUSION: Hyperuricemia is significantly associated with micro-albuminuria in middle-aged and elderly males and females from a general population in Taiwan. Elevated serum UA is an independent predictor for development of micro-albuminuria in this population.

  2. Hyperuricemia Is an Independent Risk Factor for New Onset Micro-Albuminuria in a Middle-Aged and Elderly Population: A Prospective Cohort Study in Taiwan

    Science.gov (United States)

    Chang, Hung-Yu; Lee, Pei-Hsien; Lei, Chen-Chou; Tung, Chun-Wu; Hsu, Yung-Chien; Huang, Tung-Jung

    2013-01-01

    Background Hyperuricemia is now regarded as a risk factor for cardiovascular disease. Micro-albuminuria is associated with increased risk for cardiovascular disease and chronic kidney disease. We hypothesized that elevated serum uric acid (UA) is associated with development of micro-albuminuria in the general population. Methodology/Principal Findings We conducted a community-based prospective cohort study. A total of 1862 subjects from southern Taiwan, all older than 40 years, were screened and 993 of these participants without micro-albuminuria were followed for 4 years. Urinary albumin-to-creatinine ratio was measured two times per year. A multiple linear regression model indicated that serum UA was independently associated with ln(ACR) after adjustment for 8 factors (age, sex, and 6 metabolic metrics) (β = 0.194, p<0.01). Logistic regression analysis indicated that each 1 mg/dL increase of UA was associated with a 1.42-fold increased risk of micro-albuminuria after adjustment for the same 8 factors (OR = 1.42, 95% CI: 1.27–1.59, p<0.01). A Cox regression model using subjects with serum UA less than 5 mg/dL as reference group indicated higher hazard ratios (HRs) only found in subjects with serum UA more than 7 mg/dL (HR = 3.54, 95% CI: 2.11–5.93, p<0.01) and not in subjects with serum UA of 5 to 7 mg/dL (HR = 1.30, 95% CI: 0.82–2.07, p = 0.15). Conclusion Hyperuricemia is significantly associated with micro-albuminuria in middle-aged and elderly males and females from a general population in Taiwan. Elevated serum UA is an independent predictor for development of micro-albuminuria in this population. PMID:23637835

  3. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

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    Yusuke Okazaki

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

  4. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

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    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  5. Effect of 4 years subcutaneous insulin infusion treatment on albuminuria, kidney function and HbA1c compared with multiple daily injections

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Hansen, T W; Andersen, Steen;

    2015-01-01

    AIM: The effect of insulin pump [continuous subcutaneous insulin infusion (CSII)] treatment on diabetes complications in a modern clinical setting is largely unknown. We investigated the effect of 4 years CSII treatment on HbA1c, albuminuria and kidney function compared with multiple daily inject...

  6. Plasma COOH-Terminal Proendothelin-1 A marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29)

    NARCIS (Netherlands)

    Drion, Iefke; Kleefstra, Nanne; Landman, Gijs W. D.; Alkhalaf, Alaa; Struck, Joachim; Groenier, Klaas H.; Bakker, Stephan J. L.; Bilo, Henk J. G.

    2012-01-01

    OBJECTIVE-The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-A total of 1,225 patients with ty

  7. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts

    NARCIS (Netherlands)

    van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C.; Woodward, Mark; Levey, Andrew S.; de Jong, Paul E.; Gansevoort, Ron T.

    2011-01-01

    Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta

  8. Midregional Fragment of Proadrenomedullin, New-Onset Albuminuria, and Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-30)

    NARCIS (Netherlands)

    Landman, Gijs W. D.; van Dijk, Peter R.; Drion, Iefke; van Hateren, Kornelis J. J.; Struck, Joachim; Groenier, Klaas H.; Gans, Rijk O. B.; Bilo, Henk J. G.; Bakker, Stephan J. L.; Kleefstra, Nanne

    2014-01-01

    OBJECTIVEThe midregional fragment of proadrenomedullin (MR-proADM) is a marker of endothelial dysfunction and has been associated with a variety of diseases. Our aim was to investigate whether MR-proADM is associated with new-onset albuminuria and cardiovascular (CV) and all-cause mortality in patie

  9. Clinical Commentary: How to Choose Blood Pressure Goals and Treatment: Influence of Estimated Glomerular Filtration Rate and Albuminuria

    Science.gov (United States)

    Weir, Matthew R.

    2008-01-01

    Objective measures of cardiovascular disease are often lacking until patients develop symptoms associated with either coronary, cerebral or peripheral vascular disease. Estimating risk for cardiovascular disease is often based on classic Framingham Heart Study criteria, such as age, gender, blood pressure, cholesterol, glucose levels and family history. Moreover, there is a well described continuous relationship between blood pressure, cholesterol, and glucose and risk for cardiovascular events. Estimating GFR, using simple formulae, and screening quantitatively for albuminuria may provide an important opportunity for identifying patients at increased risk for cardiovascular events. These safe, simple and cost-effective measures of estimating cardiovascular disease risk can be used not only to estimate cardiovascular disease burden, but also to gauge the adequacy of response to cardiovascular risk-reducing therapies. PMID:18596856

  10. Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia

    Science.gov (United States)

    Flanagan, Jonathan M.; Alvarez, Ofelia A.; Nelson, Stephen C.; Aygun, Banu; Nottage, Kerri A.; George, Alex; Roberts, Carla W.; Piccone, Connie M.; Howard, Thad A.; Davis, Barry R.; Ware, Russell E.

    2016-01-01

    Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation. PMID:27711207

  11. Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III, 1991-1994

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    Chang Man-huei

    2010-11-01

    Full Text Available Abstract Background Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria. Methods We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994 of the Third National Health and Nutrition Examination Survey (NHANES III, a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR, as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models. Results Variants in several genes were found to be marginally associated (uncorrected P value IL1B (rs1143623 among Mexican Americans remained significantly associated with increased odds, while IL1B (rs1143623, CRP (rs1800947 and NOS3 (rs2070744 were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P TNF rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within MBL2, CRP, ADRB2, IL4R, NOS3, and VDR were significantly associated (FDR-P Conclusions Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the

  12. Cross-sectional association of serum C-reactive protein and uric acid with albuminuria in Chinese type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    LING Yan; LI Xiao-mu; GAO Xin

    2013-01-01

    Background Evidences show that subclinical chronic inflammation is involved in the pathogenesis of diabetic nephropathy.The aim of this study was to examine the relationship between serum C-reactive protein (CRP),serum uric acid,and albuminuria in Chinese type 2 diabetic patients.Methods A total of 1162 type 2 diabetic patients were recruited.All participants had relevant clinical and laboratory measurements.CRP was measured using a particle enhanced immunoturbidimetric assay.Results In the multiple linear regression model,natural log-transformed CRP (InCRP) and uric acid were independent predictors of natural log-transformed urinary albumin to creatinine ratio (InACR) (β=0.18,95% CI 0.10-0.27,P <0.001 and β=0.18,95% CI 0.09-0.27,P <0.001).The interaction of InCRP with uric acid was also associated with InACR (β=0.04,95% CI 0.02-0.06,P <0.001).In the full-adjusted logistic regression model,the OR for albuminuria of the patients in the third tertile levels of CRP and uric acid was 3.94 compared with patients in the first tertile levels of CRP and uric acid (95%CI 1.73-8.94,P <0.001).Conclusions Elevated serum CRP and increased serum uric acid level were associated with albuminuria in Chinese type 2 diabetic patients.Moreover,CRP and uric acid had an interactive effect on albuminuria.

  13. Reduced albuminuria during early and aggressive antihypertensive treatment of insulin-dependent diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Smidt, U M;

    1981-01-01

    Urinary albumin excretion rate (radial immunodiffusion), glomerular filtration rate (GFR) (single-shot 51Cr-EDTA technique), and arterial blood pressure (BP) were measured in 12 juvenile-onset, insulin-dependent diabetic patients with persistent proteinuria (greater than 0.5 g/day) due to diabetic...... nephropathy. Mean age of the patients was 30 yr. All patients had a diastolic blood pressure greater than or equal to 95 mm Hg. Metoprolol, hydralazine, and furosemide or thiazide were used as antihypertensives. During the 12-mo treatment period, BP decreased from 151/104 to 133/85 mm Hg (P less than 0.......001), the urinary albumin excretion rate diminished from 1447 to 613 micrograms/min (P less than 0.005), and GFR declined from 96 to 89 ml/in/1.73 m2 (P less than 0.01). A linear relationship between mean blood pressure and the logarithm of the albuminuria was found (r = 0.48, P less than 0.01). Arterial...

  14. Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients.

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    Kuei-Mei Chou

    Full Text Available OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL and liver-type fatty acid binding protein (L-FABP are emerging as excellent biomarkers in the urine and plasma for the early prediction of acute and chronic kidney injury. The aims of this prospective study were to determine the role of albuminuria, and that of serum and urine levels of NGAL and L-FABP as predictors of a decline in the glomerular filtration rate (GFR in patients with type 2 diabetes. METHODS: A longitudinal cohort study with one hundred forty type 2 diabetic patients was conducted. Serum and urine levels of NGAL and L-FABP, and the urine albumin excretion rate were determined. The correlation between the kidney injury biomarkers and rate of GFR decline was analyzed. RESULTS: The eGFR of study subjects decreased significantly as the study progressed (86.4±31.1 vs. 74.4±27.3 ml/min/1.73 m(2, P<0.001, and the urine albumin excretion rate increased significantly (264.9±1060.3 vs. 557.7±2092.5 mg/day, P = 0.009. The baseline urine albumin excretion rate and serum L-FABP level were significantly correlated with baseline eGFR (P<0.05. The results of regression analysis for the correlations between the rate of eGFR change and the baseline levels of NGAL and L-FABP, and the urine albumin excretion rate showed that only the urine albumin excretion rate was significantly correlated with the rate of eGFR change (standardized coefficients: -0.378; t: -4.298; P<0.001. CONCLUSIONS: Tubular markers, such as NGAL and L-FABP, may not be predictive factors associated with GFR decline in type 2 diabetic patients.

  15. 中医药为主治疗肾性蛋白尿临床研究%Clinical Progress of Traditional Chinese Medicine in Treatment of Renal Albuminuria

    Institute of Scientific and Technical Information of China (English)

    吕恩君

    2013-01-01

    蛋白尿(proteinuria)是以肾小球滤过屏障结构及功能异常为主要病理基础,肾脏对血液正常超滤作用受损以及肾小管重吸收功能受损的结果.蛋白尿是肾损害的标志物,也是肾衰发生发展中起决定作用的因素之一.西医治疗肾性蛋白尿主要采用糖皮质激素、免疫抑制剂等.此类治疗方法虽有较满意的疗效,但同时亦使人体免疫力下降,导致感染等严重并发症.近年来随着深入探寻肾性蛋白尿的发病机制,中医药为主治疗肾性蛋白尿取得了较好的临床进展.%The glomerular filtration harrier structure and dysfunction are the main pathological basis of proteinuria, and it is the outcome of kidney damage and blood ultrafiltration dysfunction. Proteinuria is not only a sign of kidney damage, but also plays a decisive role in the development of renal failure. Western medicine for treatment of renal albuminuria is glucocorticoids and immunosuppressive agents. Such treatments have more satisfactory results, but they make the human body immunity reduce, leading to severe complications such as infection. In recent years, with the in-depth exploration of renal albuminuria pathogenesis, TCM and Chinese herbs for treatment of renal albuminuria have achieved good clinical progress.

  16. Prevalence of and factors associated with albuminuria in the Korean adult population: the 2011 Korea National Health and Nutrition Examination Survey.

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    Jong Chul Won

    Full Text Available BACKGROUND: Microalbuminuria is associated with increased risk of renal disease and cardiovascular diseases even in non-diabetic subjects. High incidence rates of microalbuminuria have been found in a number of population-based studies. However, the prevalence and risk factors associated with microalbuminuria in the general population in Korea are unclear. OBJECTIVES: The present study was performed to estimate the prevalence of microalbuminuria and investigate the associated risk factors in the general adult population using the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2 data from 2011. METHODS: A total of 5,202 participants (mean age, 45.6 years; men, 2,337; women, 2,865 were included in the analysis. Microalbuminuria was evaluated in participants of KNHANES V-2 based on the urine albumin-creatinine ratio. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. RESULTS: The weighted prevalence of microalbuminuria was 5.2% (95% CI, 4.4-6.1 in the general population. The prevalence of albuminuria is increased with age. After adjustment for age and sex, the presence of albuminuria was associated with increased waist circumference, systolic and diastolic blood pressure, aspartate aminotransferase, triglyceride, fasting plasma glucose, and the presence of hypertension and diabetes. In logistic regression analyses, older age, female sex, diabetes, hypertension, and serum aspartate aminotransferase were independently associated with the presence of albuminuria. CONCLUSION: The prevalence of microalbuminuria was found to be 5.2%, and conventional risk factors for cardiovascular diseases are closely related to the presence of microalbuminuria in Korea. Microalbuminuria may be a useful marker to identify individuals with increased risk of cardiovascular disease.

  17. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice

    OpenAIRE

    Vallon, Volker; Gerasimova, Maria; Rose, Michael A.; Masuda, Takahiro; Satriano, Joseph; Mayoux, Eric; Koepsell, Hermann; Thomson, Scott C.; Rieg, Timo

    2013-01-01

    Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60–80 mg·kg−1·day−1) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upr...

  18. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy : Post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial

    NARCIS (Netherlands)

    Eijkelkamp, Wouter B. A.; Zhang, Zhongxin; Remuzzi, Giuseppe; Parving, Hans-Henrik; Cooper, Mark E.; Keane, William F.; Shahinfar, Shahnaz; Gleim, Gilbert W.; Weir, Matthew R.; Brenner, Barry M.; de Zeeuw, Dick

    2007-01-01

    Albuminuria reduction could be renoprotective in hypertensive patients with diabetic nephropathy. However, the current use of renin-angiotensin-system intervention is targeted to BP only. Therefore, this study investigated the adequacy of this approach in 1428 patients with hypertension and diabetic

  19. LONG-TERM EFFECTS OF LINOLEIC-ACID-ENRICHED DIET ON ALBUMINURIA AND LIPID-LEVELS IN TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS WITH ELEVATED URINARY ALBUMIN EXCRETION

    NARCIS (Netherlands)

    DULLAART, RPF; BEUSEKAMP, BJ; MEIJER, S; HOOGENBERG, K; VANDOORMAAL, JJ; SLUITER, WJ

    1992-01-01

    We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200-mu-g/min

  20. Impacts of chronic kidney disease and albuminuria on associations between coronary heart disease and its traditional risk factors in type 2 diabetic patients – the Hong Kong diabetes registry

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    Cockram Clive S

    2007-12-01

    Full Text Available Abstract Background Glycated haemoglobin (HbA1c, blood pressure and body mass index (BMI are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD may influence the effects of other risk factors on coronary heart disease (CHD. Methods A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings. Results Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC, high density lipoprotein cholesterol (HDL-C and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L. Conclusion In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.

  1. Remission of nephrotic-range albuminuria reduces risk of end-stage renal disease and improves survival in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Rossing, K; Christensen, P K; Hovind, Peter;

    2005-01-01

    AIMS/HYPOTHESIS: We evaluated the impact of remission of nephrotic-range albuminuria (>2500 mg/24 h) (NRA) on end-stage renal disease (ESRD) and mortality in type 2 diabetic patients with nephropathy. METHODS: This was a follow-up observational study involving all 79 patients (35%; 62 men, 17 women......) with NRA from a cohort of type 2 diabetic patients with nephropathy that was followed for at least 3 years at the Steno Diabetes Center (n=227). Patients were followed from the onset of NRA until death or January 2005. The mean age (+/-SD) was 60+/-8 years and known diabetes duration was 14+/-7 years...... associated with an increased risk of ESRD and death. CONCLUSIONS/INTERPRETATION: Aggressive antihypertensive treatment can lead to long-term remission of NRA in a sizeable proportion of patients with type 2 diabetes. Such remission is associated with a slower progression of nephropathy and substantially...

  2. Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy.

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    Susan Yung

    Full Text Available OBJECTIVE: Sulodexide is a mixture of glycosaminoglycans that may reduce proteinuria in diabetic nephropathy (DN, but its mechanism of action and effect on renal histology is not known. We investigated the effect of sulodexide on disease manifestations in a murine model of type I DN. METHODS: Male C57BL/6 mice were rendered diabetic with streptozotocin. After the onset of proteinuria, mice were randomized to receive sulodexide (1 mg/kg/day or saline for up to 12 weeks and renal function, histology and fibrosis were examined. The effect of sulodexide on fibrogenesis in murine mesangial cells (MMC was also investigated. RESULTS: Mice with DN showed progressive albuminuria and renal deterioration over time, accompanied by mesangial expansion, PKC and ERK activation, increased renal expression of TGF-β1, fibronectin and collagen type I, III and IV, but decreased glomerular perlecan expression. Sulodexide treatment significantly reduced albuminuria, improved renal function, increased glomerular perlecan expression and reduced collagen type I and IV expression and ERK activation. Intra-glomerular PKC-α activation was not affected by sulodexide treatment whereas glomerular expression of fibronectin and collagen type III was increased. MMC stimulated with 30 mM D-glucose showed increased PKC and ERK mediated fibronectin and collagen type III synthesis. Sulodexide alone significantly increased fibronectin and collagen type III synthesis in a dose-dependent manner in MMC and this increase was further enhanced in the presence of 30 mM D-glucose. Sulodexide showed a dose-dependent inhibition of 30 mM D-glucose-induced PKC-βII and ERK phosphorylation, but had no effect on PKC-α or PKC-βI phosphorylation. CONCLUSIONS: Our data demonstrated that while sulodexide treatment reduced proteinuria and improved renal function, it had differential effects on signaling pathways and matrix protein synthesis in the kidney of C57BL/6 mice with DN.

  3. High-normal serum uric acid is associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; HAN Xue-yao; JI Li-nong

    2011-01-01

    Background Recently,some studies had shown that elevated serum uric acid (SUA) itself may increase the risk for development of renal disease in patients with diabetes.This study aimed to explore whether SUA was a predictor of microalbuminuria and impaired renal function in type 2 diabetes in Chinese patients.Methods This cross-sectional study included 2108 type 2 diabetic patients.Kidney function was estimated using the simplified modification of diet in renal disease (MDRD) equation to obtain estimated glomerular filtration rate.The urine samples were obtained for measuring the albumin-to-creatinine ratio (ACR).Results According to the ACR level,these patients were divided into two groups,normal ACR (NA) and non-normal ACR (non-NA).Both SUA and creatinine were significantly higher in the non-NA group than those in the NA group ((318.89+107.52) vs.(283.44±88.64) μmol/L,and (95.08±53.24) vs.(79.63±18.20) μmol/L,respectively).Logistic regression analysis showed that diabetic duration,systolic blood pressure,creatinine and SUA were the independent predictors of albuminuria.Furthermore,to identify the factors associated with renal function,these patients were divided into two groups according to the MDRD level (MDRD<90 or MDRD>90).Both SUA and creatinine were significantly higher in the lower MDRD group than those in the higher MDRD group ((301.90±96.46) vs.(264.07+84.74) μmol/L,and (89.10±31.00) vs.(66.37±11.15) μ mol/L,respectively).Logistic regression analysis showed that only age and SUA were the independent predictors of MDRD.Conclusion High-normal SUA was associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients.

  4. The impact of chronic kidney disease and albuminuria on coronary artery disease%慢性肾病及尿蛋白阳性对冠状动脉病变的影响

    Institute of Scientific and Technical Information of China (English)

    刘晶淼; 贾大林; 周维

    2010-01-01

    目的 研究慢性肾病患者冠状动脉病变特点及尿蛋白阳性对冠状动脉病变的影响.方法 根据基础肾小球滤过率(GFR)将连续299例接受冠状动脉造影患者分为三组:144例GFR>90ml/(min·1.73m~2)为肾功能正常组;97例GFR 60~90ml/(min·1.73m~2)为肾功能轻度减退组;58例GFR90 ml/(min·1.73m~2)],group Ⅱ[97 patients with mild renal impairment,GFR 60-90 ml/(min·1.73 m~2)]and group Ⅲ[58 patients with medium renal impairment,GFR < 60 ml/(min·1.73 m2~)].Then according to the albuminuria,patients were divided into 2 groups:the albuminuria negative group(171 patients)and albuminuria positive group(128 patients).Clinical features and coronary lesion characteristics were compared among the groups.Results In group Ⅰ,Ⅱ,Ⅲ,the incidence rate of coronary heart disease was 66.7%(96/144),70.1%(68/97),72.4%(42/58),the incidence rate of three-vessel coronary lesion was 9.7%(14/144),20.6%(20/97),22.4%(13/58),the incidence rate of left anterior descending artery lesion was 50.7%(73/144),56.7%(55/97),60.3%(35/58),and coronary jeopardy score was(15±15),(19+20),(22 ± 21)scores,respectively.There was significant difference among them(P <0.05).In albuminuria negative group and positive group,the incidence rate of coronary heart disease was 64.3%(110/171),75.0%(96/128),the incidence rate of three-vessd coronary lesion was 11.1%(19/171),21.9%(28/128),the incidence rate of left anterior descending artery lesion was 49.1%(84/171),61.7%(79/128),and coronary jeopardy score was(15 ±16),(20 ± 20)scores,respectively.There was significant difference between the two groups(P <0.05).Conclusions Chronic kidney dysfunction and albuminuria may be an important factor determining the occurrence and the severity of coronary artery disease.Especially it is more significant to inspect albuminuria at the early stage of kidney dysfunction.

  5. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

    Science.gov (United States)

    Gallo, Linda A.; Ward, Micheal S.; Fotheringham, Amelia K.; Zhuang, Aowen; Borg, Danielle J.; Flemming, Nicole B.; Harvie, Ben M.; Kinneally, Toni L.; Yeh, Shang-Ming; McCarthy, Domenica A.; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M.

    2016-01-01

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted. PMID:27226136

  6. Flow Mediated Dilatation Is Reduced with the Progressive Stages of Glomerular Filtration Rate and Albuminuria in Type 2 Diabetic Patients without Coronary Heart Disease

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    Hiroyuki Ito

    2015-01-01

    Full Text Available We aimed to clarify the usefulness of measuring the flow mediated dilatation (FMD in patients with type 2 diabetes mellitus without and with coronary heart disease (CHD. The FMD was measured in 480 patients with type 2 diabetes and in 240 nondiabetic subjects. The FMD was significantly lower in the subjects with CHD (n = 145, 5.4±3.2% than in those without CHD (n = 95, 6.9±3.5% among the nondiabetic subjects. The FMD was also lower in the subjects both with CHD (n = 161, 5.6±2.8% and without CHD (n = 319, 6.1±3.3% among the patients with diabetes compared to those without both diabetes and CHD. The FMD showed a significant positive correlation with the estimated glomerular filtration rate (eGFR in the diabetic patients without CHD, while there was no significant association in those with CHD. The FMD was significantly lower with the progressive stages of the GFR or albuminuria in the patients without CHD among those with diabetes, although the FMD was not different in those with CHD. In conclusion, the FMD is considered to be useful for the detection of atherosclerosis in patients with type 2 diabetes, even if overt macroangiopathy is not diagnosed.

  7. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice.

    Science.gov (United States)

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M

    2016-01-01

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted. PMID:27226136

  8. 2型糖尿病患者蛋白尿与糖尿病视网膜病变的相关性研究%Relationship of albuminuria and diabetic retinopathy in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    周晓芳

    2013-01-01

    Objective To study the relationship between the albuminuria to diabetic retinopathy in type 2 diabetic patients. Methods 70 patients with type 2 diabetes were screened in our hospital, according the patients with diabetic nephropathy or not to divided into the observation group(albuminuria group) 35 cases and the control group(without albuminuria group) 35 cases, all of the patients were given fundus examination, observed the happening situation with retinopathy. Results The notably of diabetic retinopathy in the observation group cases higher than the control group, the difference have statistically significant(P<0.05). Conclusion The patients with type 2 diabetes abnormal proteinuria in retinopathy have higher risk for diabetic retinopathy.%目的:探讨2型糖尿病患者蛋白尿与糖尿病视网膜病变发病率的关系。方法将2010年3月-2013年2月我院2型糖尿病患者70例分为观察组(蛋白尿组)与对照组(无蛋白尿组)各35例,均给予眼底检查,观察两组患者视网膜病变的发生情况。结果观察组发生糖尿病视网膜病变的比例明显高于对照组(P<005)。结论2型糖尿病患者蛋白尿与糖尿病视网膜病变存在明显相关,伴有蛋白尿的2型糖尿病患者发生视网膜病变具有较高的风险性。

  9. Current progress of the prevalence of albuminuria and its influencing factors%人群白蛋白尿发生率及影响因素的研究进展

    Institute of Scientific and Technical Information of China (English)

    王华斌; 刘蕊

    2014-01-01

    目前尿白蛋白的检测已经广泛应用于肾早期损伤的筛查.近几年来有不少国内外学者通过对大众人群的白蛋白尿发生率进行调查研究,发现白蛋白尿在大众人群中存在着较高的发生率,并且白蛋白尿的发生与肥胖、血脂代谢异常、糖代谢异常、高血压以及生活习性等因素显著相关.同时,不少研究表明白蛋白尿的发生是心血管疾病进展、风险评估以及过早死亡的独立因素,对心血管疾病死亡率预测和全因死亡率预测有重要价值.%Currently the detection of albumin excretion rate is widely used to screen early renal injury.In recent years,there are many researches about the prevalence of albuminuria in the general population around the world,showing the high prevalence of albuminuria in the general population,and indicating that the increased albumin in urine is significantly correlated with obesity,abnormal lipid metabolism,abnormal glucose metabolism,hypertension and life habits.Meanwhile,numerous studies find that albuminuria is an independent risk factor for the progression and risk evaluation of cardiovascular disease and all-cause mortality,it can be a useful predictor of cardiovascular mortality and all-cause mortality in the general population.

  10. Aliskiren suppresses the renin–angiotensin–aldosterone system and reduces blood pressure and albuminuria in elderly chronic kidney disease patients with hypertension

    Directory of Open Access Journals (Sweden)

    Morishita Y

    2012-09-01

    patients with hypertension.Keywords: aliskiren, renin–angiotensin–aldosterone system, blood pressure, albuminuria, elderly chronic kidney disease

  11. Albuminuria as a Risk Factor for Anemia in Chronic Kidney Disease: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD.

    Directory of Open Access Journals (Sweden)

    Ji Suk Han

    Full Text Available Anemia is a common complication among patients with chronic kidney disease (CKD, and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR. We assessed the association of the urinary albumin-to-creatinine ratio (ACR and eGFR with anemia in CKD patients.We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD. Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m2 and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%. Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g as a reference group; 30-299 mg/g, adjusted odds ratio (OR = 1.43, 95% confidence interval (CI = 0.88-2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12-3.10. In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m2.The present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR.

  12. Application value of random micro-albuminuria and creatinine ratio for nursing and monitoring of preeclampsia%随机尿微量蛋白肌酐比对子痫前期护理监测的应用价值

    Institute of Scientific and Technical Information of China (English)

    李俊; 邓佩瑛; 吴瑜瑜

    2012-01-01

    Objective: To analyze the correlation between random micro - albuminuria and creatinine ratio and preeclampsia retrospectively, explore the application value of random micro - albuminuria and creatinine ratio for nursing and monitoring of preeclampsia. Methods; A total of 69 patients with preeclampsia who were treated in departments of gynecology and obstetrics, departments of critical care medicine in the hospital and Southern hospital affiliated to Southern medical university from October 2011 to February 2012 were selected, then they were divided into mild preeclampsia group and severe preeclampsia group according to random micro - albuminuria and creatinine ratio, the perinatal outcomes of pregnant women in the two groups were compared, Results; There was no statistically significant difference in age and BMI between the two groups- Systolic blood pressure, diastolic blood pressure, gestational weeks at delivery, and 24 - hour urine protein level in severe preeclampsia group were statistically significantly higher than those in mild preeclampsia group ( P < 0, 05) . The birth weight of neonates in severe preeclampsia group was statistically significantly lower than that in mild preeclampsia group ( P < 0.05 ) , The incidence of adverse pregnancy outcome in mild preeclampsia group was statistically significantly lower than that in severe preeclampsia group. Conclusion: Random micro - albuminuria and creatinine ratio can reflect the severity of preeclampsia in pregnant women rapidly and simply, which has high application value for nursing and monitoring of preeclampsia.%目的:回顾性分析孕妇随机尿微量蛋白肌酐比(ACR)水平与子痫前期的相关性,探讨ACR对子痫前期护理监测的应用价值.方法:选择2011年10月~2012年2月深圳市妇幼保健院、南方医科大学南方医院妇产科及重症医学科收治的子痫前期患者69例,根据ACR水平将患者分为轻度组和重度组,比较两组孕妇的围产结局.结果:

  13. Measurement, interpretation, and implications of proteinuria and albuminuria.

    Science.gov (United States)

    Grauer, Gregory F

    2007-03-01

    Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats. PMID:17336676

  14. Perspectives on randomized clinical trials : the case for albuminuria

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo Jan

    2008-01-01

    Large scale randomized clinical trials are needed to detect small but meaningful effects of new drugs. However, large scale randomized clinical trials are expensive undertakings and they are in imbalance with the scientific output. As a consequence there is a strong voice for more efficacious random

  15. Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia

    DEFF Research Database (Denmark)

    Hansen, J M; Olsen, Niels Vidiendal; Feldt-Rasmussen, B;

    1994-01-01

    The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid...... groups. Exercise did not reveal any further renal dysfunction. In both groups, high altitude increased TERalb from 4.8 to > 6.7%/h (P function and independent of effects of isradipine on filtration fraction...... and passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb...

  16. The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Coll, Blai; Andress, Dennis;

    2014-01-01

    with a significant increase in weight and a reduction in hemoglobin, but rates of peripheral edema, heart failure, or other side effects did not differ between groups. However, more patients treated with 1.25 mg/d atrasentan discontinued due to adverse events. After stopping atrasentan for 30 days, measured...

  17. [Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes].

    Science.gov (United States)

    Mathison Natera, Y; Finol, H J; Quero, Z; González, R; González, J

    2010-01-01

    Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

  18. Abnormal albuminuria and blood pressure rise in incipient diabetic nephropathy induced by exercise

    DEFF Research Database (Denmark)

    Christensen, Cramer

    1984-01-01

    diastolic blood pressure was elevated [92.1 mm Hg +/- 6.0 (mean +/- SD)] compared to D2 (80.9 mm Hg +/- 4.8, 2P = 0.003%) and C (79.5 mm Hg +/- 12.4, 2P = 1.2%). Baseline systolic blood pressure was not significantly different in the three groups, but systolic blood pressure was more elevated at 600 kpm....../min in D3 (193.0 mm Hg +/- 23.0) compared to D2 (170.5 +/- 17.3, 2P = 1.2%) and C (157.5 mm Hg +/- 20.9, 2P = 0.07%). Baseline albumin excretion in D3 was 82.6 micrograms/min X/ divided by 2.5 (geometric mean X/ divided by tolerance factor) and during exercise the maximal albumin excretion rose to 195...

  19. Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes

    DEFF Research Database (Denmark)

    Jorsal, Anders; Petersen, Emilie Hein; Tarnow, Lise;

    2013-01-01

    AIM: Urinary adiponectin (u-adiponectin) excretion has been suggested to reflect early glomerular damage. Inspired by this, we studied the levels of u-adiponectin in type 1 diabetic patients with different levels of urinary albumin excretion (UAE). METHODS: U-adiponectin was analysed by ELISA in...... type 1 diabetic patients: Fifty-eight with normoalbuminuria (<30mg albumin/24h), 43 with persistent microalbuminuria (30-300mg/24h) and 44 with persistent macroalbuminuria (>300mg/24h). For comparison, a control group of 55 healthy individuals was included. RESULTS: U-adiponectin increased with...... increasing levels of UAE (p<0.01). U-adiponectin median (interquartile range): Normoalbuminuria 0.38 (0.14-1.31), microalbuminuria 1.12 (0.20-2.68), macroalbuminuria 9.20 (1.10-23.35) and controls 0.09 (0.06-0.24) μg/g creatinine. Levels were unrelated to sex, age, cholesterol, diastolic BP and BMI. U-adiponectin...

  20. Albuminuria and its correlates in an Iranian type 2 diabetic population

    OpenAIRE

    Meysamie Alipasha; Hamidi Sepehr; Aghamohammadzadeh Naser; Esfahanian Fatemeh; Esteghamati Alireza; Nakhjavani Manouchehr; Abbasi Mehrshad

    2008-01-01

    Abstract Objective To study the prevalence and correlates of increased urinary albumin excretion (UAE) in an Iranian type 2 diabetic population. Methods Over a one year period since October 2002, 400 consecutive type 2 diabetic patients referred to an outpatient diabetes clinic, were enrolled in a cross sectional study. Subjects had no history of renal impairment or overt proteinuria. Data concerning demographic characteristics and cardiovascular risk factors were recorded and height, weight ...

  1. Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia

    DEFF Research Database (Denmark)

    Hansen, J M; Olsen, N V; Feldt-Rasmussen, B;

    1994-01-01

    groups. Exercise did not reveal any further renal dysfunction. In both groups, high altitude increased TERalb from 4.8 to > 6.7%/h (P < 0.05). In conclusion, acute altitude hypoxia increases Ualb despite unchanged tubular function and independent of effects of isradipine on filtration fraction. The......The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid and...... passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb...

  2. Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz;

    2007-01-01

    as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased...... in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P ICAM-1 increased from group C to group A; e.g. ICAM-1 [median (interquartile...... range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P ICAM-1 correlated (r = 0.38, P ICAM-1, respectively). CONCLUSION...

  3. Classification of Kidney Transplant Recipients Using a Combination of Estimated GFR and Albuminuria Reflects Risk

    Science.gov (United States)

    White, Christine A.; Akbari, Ayub; Talreja, Hari; Lalani, Neha; Knoll, Greg A.

    2016-01-01

    Background The 2012 Kidney Dialysis Initiative Global Outcomes chronic kidney disease (CKD) classification scheme subdivides stage 3 CKD and incorporates the urinary albumin-to-creatinine ratio (ACR). The aim of this study was to evaluate whether the novel scheme provides graded risk in kidney transplant recipients (KTRs). Methods Prevalent KTRs with available laboratory data were included. The primary outcome was a composite of doubling of serum creatinine, graft failure, or death. Patients were stratified using the CKD-Epidemiolgic Collaboration equation, and ACR and the event rate per 1000 patient-years in each CKD category were calculated. Results There were 269 KTRs with a mean follow-up of 4.5 ± 2.0 years. There was a graded increase in outcomes with increasing ACR and decreasing estimated glomerular filtration rate (eGFR). For the primary outcome, the event rate was 15.3 (95% confidence interval, 4.2-39.2) per 1000 patient-years for those with an eGFR greater than 60 mL/min per 1.73 m2 and an ACR less than 30 mg/g, whereas it was 375 (95% confidence interval, 193.8-655.1) for those with an eGFR less than 30 mL/min per 1.73 m2 and an ACR greater than 300 mg/g. Conclusions The novel Kidney Dialysis Initiative Global Outcomes classification scheme provides graded risk for important clinical events in KTRs. This information can be used to identify high-risk patients and to tailor follow-up and management strategies aimed at improving outcomes.

  4. Serum D-dimer concentrations in nephrotic syndrome track with albuminuria, not estimated glomerular filtration rate.

    LENUS (Irish Health Repository)

    Sexton, D J

    2012-01-01

    The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship.

  5. Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria

    NARCIS (Netherlands)

    Heerspink, Hiddo Lambers; Greene, Tom; Lewis, Julia B.; Raz, Itamar; Rohde, Richard D.; Hunsicker, Lawrence G.; Schwartz, Sherwyn L.; Aronoff, Stephen; Katz, Murray A.; Eisner, Gilbert M.; Mersey, James H.; Wiegmann, Thomas B.

    2008-01-01

    Background. Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized t

  6. Assessment of stress & related albuminuria in caregivers of severe mentally ill persons

    OpenAIRE

    Anirban Dalui; Prathama Guha; De, Angshuman; Sandip Chakraborty; Indranil Chakraborty

    2014-01-01

    Background & objectives: The family caregivers of patients with chronic diseases are known to undergo psychiatric stress leading to oxidative damage to glomerular membrane of kidney resulting in proteinuria. This study was aimed to compare current anxiety, depression levels and urinary albumin:creatinine ratio between primary caregivers of chronic mental patients and matched controls, and also whether the urinary albumin : creatinine ratio is correlated with stress factors (state and trait an...

  7. Aminaphtone therapy in patients with type 1 diabetes and albuminuria: a case report

    OpenAIRE

    Romano, Concetta; Tamburella, Consuelo; Costa, Martino; Messina, Marco; Fassari, Anna Lisa; Bertini, Marco

    2014-01-01

    Introduction Microalbuminuria in type 1 diabetes is the earliest manifestation of diabetic microangiopathy (nephropathy). To date, the pharmacological approach to microangiopathy has not been shown to be useful. By using aminaphtone to control nephrologic complications of insulin-dependent diabetes mellitus we first obtained a significant improvement in microalbuminuria confirming this new pharmacological approach for insulin-dependent diabetes mellitus organospecific complications control. C...

  8. EFFECT OF A SOMATOSTATIN ANALOG, OCTREOTIDE, ON RENAL HEMODYNAMICS AND ALBUMINURIA IN ACROMEGALIC PATIENTS

    NARCIS (Netherlands)

    DULLAART, RPF; MEIJER, S; MARBACH, P; SLUITER, WJ

    1992-01-01

    Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma fl

  9. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    OpenAIRE

    Šoupal, J.; G. Loni Ekali; Prázný, M.; Kalousová, M; Kvasnička, J.; L. Landová; Zima, T.; Škrha, J.

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.3...

  10. High altitude-induced albuminuria in normal man is enhanced by infusion of low-dose dopamine

    DEFF Research Database (Denmark)

    Hansen, J M; Kanstrup, I L; Richalet, J P;

    1996-01-01

    flow (ERPF) from 465 ml min-1 (412-503) to 410 ml min-1 (385-451) (p filtration fraction from 24% (22-27) to 28% (26-29) (p Glomerular filtration rate (GFR), and the renal clearances of lithium (CLi) and sodium (CNa) remained unchanged at high altitude. Dopamine...... excretion rate of albumin, which is further increased by the renal vasodilating drug dopamine. This effect of dopamine at high altitude may result from combined effects of the increase in renal plasma flow and a hypoxia-induced increase in the glomerular capillary permeability to albumin.......Renal function and the urinary excretion rate of albumin (Ualb) at rest and during infusion of dopamine (3 micrograms kg-1 min-1) were investigated in eight normal volunteers at sea level and 48 h after a rapid, passive ascent to an altitude of 4350 m. Oxygen saturation decreased to 81% (77...

  11. Aliskiren in combination with losartan reduces albuminuria independent of baseline blood pressure in patients with type 2 diabetes and nephropathy

    DEFF Research Database (Denmark)

    Persson, Frederik; Lewis, Julia B; Lewis, Edmund J;

    2011-01-01

    Elevated BP contributes to development and progression of proteinuria and decline in renal function in patients with type 2 diabetes. Our post hoc analysis assessed the baseline BP influence on the antiproteinuric effect in the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study....

  12. Effects of isradipine in Type 1 (insulin-dependent) diabetic patients with albuminuria and normal blood pressure

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Feldt-Rasmussen, B

    1992-01-01

    The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin...... excretion (more than 30 mg/24h) based on several 24 h urine collections, and BP was normal (below 140/90 mmHg). After a placebo treatment period of eight weeks the patients were randomly assigned to two groups for a double-blind crossover study. Each patient received either 2.5 mg isradipine twice daily...... or placebo for eight weeks. Then, after 4 weeks (the wash-out period), each patient received the drug he or she had not taken before for another 8 weeks. Systolic blood pressure was lowered by 8 mmHg from 127 (114-139) mmHg (P less than 0.01) and diastolic by 5 mmHg from 81 (70-87) mmHg (P less than 0...

  13. Effective risk stratification in patients with moderate cardiovascular risk using albuminuria and atherosclerotic plaques in the carotid arteries

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Sehestedt, Thomas;

    2015-01-01

    /mmol in men/women. The composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic heart disease was recorded (n = 229). RESULTS: Both elevated UACR (P = 0.002) and atherosclerotic plaques (P ..., Systematic COronary Risk Evaluation (SCORE), and Framingham risk score (FRS) groups. Subclinical vascular damage was defined as carotid-femoral pulse wave velocity at least 12 m/s, and carotid atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 90th percentile of 0.73/1.06 mg...

  14. Clinical Commentary: How to Choose Blood Pressure Goals and Treatment: Influence of Estimated Glomerular Filtration Rate and Albuminuria

    OpenAIRE

    Weir, Matthew R

    2008-01-01

    Objective measures of cardiovascular disease are often lacking until patients develop symptoms associated with either coronary, cerebral or peripheral vascular disease. Estimating risk for cardiovascular disease is often based on classic Framingham Heart Study criteria, such as age, gender, blood pressure, cholesterol, glucose levels and family history. Moreover, there is a well described continuous relationship between blood pressure, cholesterol, and glucose and risk for cardiovascular even...

  15. Association between albuminuria, atherosclerotic plaques, elevated pulse wave velocity, age, risk category and prognosis in apparently healthy individuals

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Blyme, Adam;

    2014-01-01

    .4, 20.6% or 7.9, 8.2, 16.6, 19.5% or 6.6, 7.6, 9.8, 20.0%) increased, all P aged 61 or 71 years, with moderate or very high SCORE or intermediate or high FRS (all P aged 41, 51 or 61 years......, with moderate SCORE or with high-intermediate or high FRS (all P aged 51 years (P aged 51 [hazard ratio 2.7 (1.6-4.8)] and 61...... and especially atherosclerotic plaques or urine albumin/creatinine ratio (UACR) at least 0.73/1.06 mg/mmol (men/women) added prognostic information in individuals aged 51 or 61 years or with moderate or intermediate risk....

  16. Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

    LENUS (Irish Health Repository)

    Cullen, Mr

    2013-10-11

    Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin\\/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes.

  17. Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H;

    2010-01-01

    The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-American...

  18. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

    OpenAIRE

    Linda A. Gallo; Ward, Micheal S.; Fotheringham, Amelia K.; Aowen Zhuang; Borg, Danielle J.; Nicole B. Flemming; Harvie, Ben M.; Kinneally, Toni L.; Shang-Ming Yeh; McCarthy, Domenica A.; Hermann Koepsell; Volker Vallon; Carol Pollock; Usha Panchapakesan; Josephine M. Forbes

    2016-01-01

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In mal...

  19. Antihypertensive effects of double the maximum dose of valsartan in African-American patients with type 2 diabetes mellitus and albuminuria

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H;

    2010-01-01

    The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-A...

  20. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus

    NARCIS (Netherlands)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J L

    2016-01-01

    BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response

  1. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus

    NARCIS (Netherlands)

    Pena, Michelle J.; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J. L.

    2016-01-01

    Background: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response

  2. Association between albuminuria and expression of nephrin in diabetic rats%糖尿病大鼠蛋白尿与肾脏病理及nephrin表达的相关性研究

    Institute of Scientific and Technical Information of China (English)

    屈智慧; 杨立志; 赵颖; 肖庆飞; 崔明姬

    2011-01-01

    目的 探讨糖尿病大鼠蛋白尿的排泄量与大鼠肾脏病理改变及足细胞裂孔蛋白nephrin表达的相关性.方法 将40只Wistar大鼠分为正常组(NC n=20)、糖尿病组(DM n=20),DM组单次腹腔注射链脲菌素(STZ)50 mg/kg,建立糖尿病模型,NC组注射等量枸橼酸缓冲液.分别于0周、4周、8周、12周动态监测大鼠尿白蛋白排泄量、肾重/体重指数(KW/BW),肌酐清除率(Ccr)等.取不同时期糖尿病大鼠肾组织分别行常规病理检查和用免疫组化检测大鼠肾脏nephrin的表达.结果 与NC组相比,DM组大鼠随着糖尿病病程的延长尿白蛋白、肌酐清除率逐渐增加,肾重/体重指数增高,并且白蛋白尿早于肾功能的改变,光镜显示DM组大鼠肾小球细胞外基质增多,基底膜增厚,系膜基质增多.随着病理改变加重,肾组织内nephrin蛋白表达开始降低,在12周时最明显.结论 糖尿病大鼠出现白蛋白尿,是肾脏损伤的早期指标,随着尿蛋白的增多,肾脏病理改变加重且nephrin蛋白表达降低,提示nephrin蛋白参与糖尿病大鼠蛋白尿的产生与发展.%Objective  To observe album inuria excretion in diabetic rats and to investigate its relationships with renal tissue patho logical changes and the expression of nephrin .Methods  40 Wistar rats were divided into control group(NCn = 20) ,diabetic group(DM n =20) .Diabetes was induced by peritoneal injection of STZ 50 mg/kg .Urinary album in(U A) ,renalfuction and the ratio of kidney weight/body weight(KW/BW ) were detected dynamically at 0 ,4 ,8,12 weeks .The renal tissue were analyzed by by light microscope .Expression of nephrin was detected by immunohistochemistry .Results  Compared with NC ,with extension of the course of disease ,urinary album in ,C cr and the ratio of kidney weight/body weight in DM were gradually increased ( P < 0 .05) .Album inuria appeared earlier than abnorm alities of C cr .Histological examination of the kidney revealed increased ECM accumulation ,thickening of the glomerular basement membrane with the development of diabetic nephropathy .Nephrin was distributed asymmetry and decreased gradually on glomeruloes in diabetic group especially at 12 th week .Conclusion  Album inuria appeared earlier in diabetic rats ,which is an indicator of early damage in diabetic nephropathy .Nephrin may play a role in pathogenesis and development of the Album inuria in diabetic nephropathy .

  3. Effects of simvastatin on albuminuria in hypercholesterolemic type 2 diabetic patients%辛伐他汀对伴高胆固醇血症的2型糖尿患者白蛋白尿的影响

    Institute of Scientific and Technical Information of China (English)

    伊桂叶; 苏青

    2008-01-01

    目的 探讨辛伐他汀治疗对2型糖尿患者尿白蛋白排泄率的影响.方法 血压正常、血糖控制稳定的伴高胆固醇血症和白蛋白尿的2型糖尿患者25例,给予辛伐他汀20 mg/d,共三个月.于治疗前后测定空腹血糖、糖化血红蛋白、肌酐、尿素氮、内生肌酐清除牢、血脂、血压及尿白蛋白排泄率.结果 辛伐他汀治疗前后患者的空腹mL糖、糖化血红蛋白、肌酐、尿素氮、内生肌酐清除率、血压、血清甘油三酯和高密度脂蛋白胆同醇的变化无统计学意义(P>0.05),治疗后血清总胆同醇、低密度脂蛋白和尿白蛋白排泄率降低(P<0.01).结论 辛伐他汀治疗可降低高胆固醇血症的Z型糖尿患者尿白蛋白排泄率,提示他汀类调脂药对糖尿病肾病可能具有肾保护作用.%Objective To investigate the effects of simvastatin on urinary albumin excretion rate in pa-tients With type 2 diabetes. Methods A total of 25 normotensive hypercholesterolemic type 2 diabetic patients with microalbuminurea or macroalbuminurea were enrolled in a study for 3 months,receiving Simvastatin at dose of 20 mg/day. Fasting plasma glucose, HbA 1c, systolic blood pressure, diastolic blood pressure, blood lipid, urea nitrogen,creatinine,endogenous creatinine clearance rate and urinary albumin excretion rate were obtained be-fore and after simvastatin treatment. Results Fasting plasma glucose, HbA1 c, systolic blood pressure, diastolic blood pressure, blood tiglyceride, HDL-cholesterol, urea nityogen, creatinine and endogenous creatitine clearance rate remained unchanged after simvastatin treatment(P>0.05). Simvastatin significantly decreased plasma total cholesterol and LDL-cholesterol after 3 months of treatment (P<0.01). A concomitant significant decrease of urinary albumin excretion rate was observed during the same period (P<0.01). Conclusion Simvastatin de-creased urinary albumin excretion rate in type 2 diabetic patients with hypereholesterolemia,and statins appears to confer renoprotection in diabetes.

  4. Is it time to change the definition of normal urinary albumin excretion?

    DEFF Research Database (Denmark)

    Wachtell, K.; Olsen, M.H.

    2008-01-01

    intensive follow-up. In addition, although previous studies have indicated that cardiovascular risk increases exponentially with increasing levels of albuminuria, the definition of the threshold for albuminuria should be dependent on concomitant cardiovascular disease (i.e. lower levels of albuminuria...... at baseline and had normoalbuminuria by conventional definitions. The study showed that quartiles of albuminuria beyond the lowest quartile were increasingly predictive of subsequent hypertensive disease, even at levels well below what is conventionally considered to be the normal range. This commentary...... highlights the importance of evaluating albuminuria as an indicator of target organ damage and a risk factor for cardiovascular disease. Patients without hypertension, diabetes or other cardiovascular diseases who have albuminuria should be considered at risk of cardiovascular disease and should undergo...

  5. Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression

    NARCIS (Netherlands)

    Schutte, Elise; Gansevoort, Ron T.; Benner, Jacqueline; Lutgers, Helen L.; Lambers Heerspink, Hiddo J.

    2015-01-01

    Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by

  6. Socioeconomic disparities in chronic kidney disease : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Vart, Priya; Gansevoort, Ron T.; Joosten, Michel M.; Bultmann, Ute; Reijneveld, Sijmen A.

    2015-01-01

    CONTEXT: Evidence on the strength of the association between low SES and chronic kidney disease (CKD; measured by low estimated glomerular filtration rate [eGFR], high albuminuria, low eGFR/high albuminuria, and renal failure) is scattered and sometimes conflicting. Therefore, a systematic review an

  7. Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Sogaard, Peter; Andersen, Henrik Ullits;

    2016-01-01

    PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS:...

  8. BIOCHEMICAL SCREENING OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Vivek

    2016-01-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by the following- Persistent albuminuria (>300mg/d or >200μg/min, that is confirmed on at least 2 occasions 3-6 months apart diabetic, progressive decline in the Glomerular Filtration Rate (GFR, elevated arterial blood pressure. The earliest biochemical criteria for the diagnosis of diabetic nephropathy is the presence of micro-albumin in the urine, which if left untreated will eventually lead to End-Stage Renal Disease (ESRD. Micro-albuminuria refers to the excretion of albumin in the urine at a rate that exceeds normal limits. The current study was conducted to establish the prevalence of micro-albuminuria in a sequential sample of diabetic patients attending hospital and OPD Clinic to determine its relationship with known and putative risk factors to identify micro- and normo-albuminuric patients in their sample for subsequent comparison in different age, sex, weight and creatinine clearance of the micro- and normo-albuminuric patients. This cross-sectional analytical study was conducted in one hundred patients at Saraswathi Institute of Medical Sciences, Anwarpur, Hapur, U. P. Patients having diabetes mellitus in different age group ranging from 30 to 70 years were selected. Data was analysed by SPSS software. Micro-albuminuria was observed in 35% in patients with type 2 diabetes mellitus. It was observed that 65% patients were free from any type of albuminuria. Also micro-albuminuria was present in 10% of the patients less than 50 yrs. of age, while 15% of the patients more than 50 yrs. of age were having micro-albuminuria. There was a statistically significant correlation of micro-albuminuria with duration of diabetes. Incidence of micro-albuminuria increases with age as well as increased duration of diabetes mellitus. Our study shows that only 5% patients developed macro-albuminuria. Glycosylated haemoglobin and fasting plasma glucose was significantly raised among all these

  9. 高同型半胱氨酸血症及白蛋白尿与慢性肾脏病患者心血管疾病相关性研究%Relationships of Hyperhomocysteinemia and Albuminuria to Cardiovascular Disease in Patients with Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    韩志明; 姚筱; 刘炎

    2015-01-01

    目的:通过检测慢性肾脏病(CKD)患者临床指标及心血管疾病(CVD)的发生率,研究高同型半胱氨酸血症(HHcy)、白蛋白尿(AU)与 CKD 患者心血管疾病的相关性,探讨 HHcy、AU 对 CKD 患者发生 CVD 的预测价值。方法对292例 CKD 患者的一般情况、生化指标、心电图、胸部 X 线片、心脏超声等资料进行回顾性分析,并按血同型半胱氨酸(Hcy)与 AU 检测结果将292例患者分为4组:Hcy(-)AU(-)组、Hcy(+)AU(-)组、Hcy (-)AU(+)组、Hcy(+)AU(+)组,比较4组实验室、物理检查结果及 CVD 发生率。对 CKD 患者心血管疾病发生的危险因子行多因素 Logistic 回归分析。结果292例患者中:Hcy(-)AU(-)组66例(22.6%)、Hcy(+)AU (-)组78例(26.7%)、Hcy(-)AU(+)组62例(21.2%)、Hcy(+)AU(+)组86例(29.4%)。与 Hcy(-)AU (-)组相比,其余3组患者的年龄、SBP、DBP、CRP、UA、TC、LDL 均明显升高(P <0.05),Hb、HDL 均明显降低(P <0.05),胸部 X 线片、心电图、心脏超声异常率及 CVD 发生率均明显升高(P <0.05);与 Hcy(+)AU(+)组相比,其余3组患者的 Hb 明显升高(P <0.05),胸部 X 线片、心电图、心脏超声异常率及 CVD 发生率均明显降低(P <0.05)。CKD 患者发生 CVD 与年龄、SBP、UA、TC、AU、Hcy 呈正相关,与 Hb 呈负相关。结论 Hcy、AU 是CKD 患者心血管疾病发生的危险因子,同时 Hcy 及 AU 在预测心血管疾病的发生有协同效应。%Objective To investigate the relationships of hyperhomocysteinemia(Hcy)and al-buminuria(AU)to cardiovascular disease(CVD)in patients with chronic kidney disease(CKD) through measuring the clinical indicators and incidence of CVD,and to explore the predictive val-ues of Hcy and AU in CVD in CKD patients.Methods Data of 292 CKD patients(general condi-tions,biochemical indexes,electrocardiogram,chest X-ray films,cardiac ultrasound images,etc.) were analyzed retrospectively.According to the results of Hcy and AU measurement,these pa-tients were divided into four groups:Hcy(-)AU(-)group,Hcy(+)AU(-)group,Hcy(-) AU(+)group and Hcy(+)AU(+)group.The laboratory and physical examination findings and the incidence of CVD were compared among the four groups.The risk factors for CVD were analyzed using multivariate logistic regression analysis.Results Among the 292 patients,results were Hcy(-)AU(-)graup in 66(22.6%),Hcy(+)AU(-)graup in 78(26.7%),Hcy(-) AU(+)group in 62(21.2%),and Hcy(+)AU(+)graup in 86(29.4%).Compared with Hcy (-)AU(-)group,the age,systolic blood pressure(SBP),diastolic blood pressure(DBP),C re-active protein(CRP),uric acid(UA),total cholesterol(TC),low density lipoprotein(LDL)in-creased,the abnormal rates of chest X-ray film,electrocardiogram and echocardiogram and inci-dence of CVD elevated,and the hemoglobin(Hb)and high density lipoprotein(HDL)decreased in other three groups(P <0.05).Compared with Hcy(+)AU(+)group,the Hb increased and the abnormal rates of chest X-ray film,electrocardiogram and echocardiogram and incidence of CVD decreased in other three groups(P <0.05).The incidence of CVD was positively correlated with the age,SBP,UA,TC,AU and Hcy,but negatively correlated with the Hb in patients with CKD. Conclusion The Hcy and AU are the risk factors for CVD in patients with CKD,and they have a synergistic effect in the prediction of CVD.

  10. Comparison of the Antialbuminuric Effects of Benidipine and Hydrochlorothiazide in Renin-Angiotensin System (RAS) Inhibitor-Treated Hypertensive Patients with Albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) Study

    Science.gov (United States)

    Ando, Katsuyuki; Nitta, Kosaku; Rakugi, Hiromi; Nishizawa, Yoshiki; Yokoyama, Hitoshi; Nakanishi, Takeshi; Kashihara, Naoki; Tomita, Kimio; Nangaku, Masaomi; Takahashi, Katsutoshi; Isshiki, Masashi; Shimosawa, Tatsuo; Fujita, Toshiro

    2014-01-01

    Objective: This study evaluated the non-inferiority of renoprotection afforded by benidipine versus hydrochlorothiazide in hypertensive patients with chronic kidney disease (CKD). Methods: In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of benidipine and hydrochlorothiazide were examined in renin-angiotensin system (RAS) inhibitor-treated patients with blood pressure (BP) readings of ≥ 130/80 mmHg and ≤ 180/110 mmHg, a urinary albumin to creatinine ratio (UACR) of ≥ 300 mg/g, and an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73m2. Patients received benidipine (n = 176, final dose: 4.8 mg/day) or hydrochlorothiazide (n = 170, 8.2 mg/day) for 12 months. Results: Benidipine and hydrochlorothiazide exerted similar BP- and eGFR-decreasing actions. The UACR values for benidipine and hydrochlorothiazide were 930.8 (95% confidence interval: 826.1, 1048.7) and 883.1 (781.7, 997.7) mg/g at baseline, respectively. These values were reduced to 790.0 (668.1, 934.2) and 448.5 (372.9, 539.4) mg/g at last observation carried forward (LOCF) visits. The non-inferiority of benidipine versus hydrochlorothiazide was not demonstrated (benidipine/hydrochlorothiazide ratio of LOCF value adjusted for baseline: 1.67 (1.40, 1.99)). Conclusions: The present study failed to demonstrate the non-inferiority of the antialbuminuric effect of benidipine relative to that of hydrochlorothiazide in RAS inhibitor-treated hypertensive patients with macroalbuminuria. PMID:25013370

  11. The correlation of albuminuria and glomerular filtration rate with diabetic retinopathy in type 2 diabetes%尿白蛋白、肾小球滤过率与2型糖尿病视网膜病变的相关性研究

    Institute of Scientific and Technical Information of China (English)

    蔡芸莹; 马中书; 邱明才

    2012-01-01

    目的 比较T2DM视网膜病变(DR)不同时期,尿蛋白、肾小球滤过率(GFR)变化,寻找早期筛查DR的指标. 方法 采用回顾性病历研究,根据散瞳眼底检查分组,同期测定各组24h尿白蛋白定量,以MDRD公式计算GFR. 结果 与正常眼底组相比,DR组患者的GFR明显减低(P<0.05),且尿白蛋白(UAlb)、GFR均与DR呈显著独立相关(P<0.05). 结论 UAlb、GFR均与DR密切相关,其联合筛查有利于DR早期检出.%Objective To compare changes of urinary albumin and eGFR between different stages of diabetic retinopathy(DR) to look for early screening diabetic retinopathy indicators. Methods The clinical data were analyzed retrospectively. Diabetic retinopathy was assessed by mydriatic ophthalmoscopy. While determinating the urinary albumin quantitative for 24 hours, the estimated glomerular filtration rate(GFR) was measured by MDRD formula Results The levels of GFR were significantly lower in two DR groups than in normal retina group(P< 0. 05). Both urinary albumin(Ualb) and GFR were independently risks for diabetic retinopathy. Conclusion Ualb and GFR are closely associated with diabetic retinopathy. Clinicians need to check both urinary albumin and eGFR to screen for early diabetic retinopathy.

  12. Relationship of s coronary atherosclerosis to higher blood pressure, renal dysfunction and albuminuria in patients with type 2 diabetes%2型糖尿病患者冠状动脉粥样硬化与高血压、肾功能减退和白蛋白尿的关系

    Institute of Scientific and Technical Information of China (English)

    戎健; 余开选; 白淑蓉; 邓杰尹; 何次

    2015-01-01

    目的 探讨2型糖尿病患者冠状动脉粥样硬化(coronary atherosclerosis,CAS)与高血压、肾功能减退及白蛋白尿的关系.方法 采用320排螺旋CT对247例无冠心病史的2型糖尿病患者进行检查,并测定血压、空腹血糖、糖化血红蛋白、血脂、肾小球滤过率估计值(estimated glomerular filtration rate,eGFR)和尿白蛋白排泌率等.结果 2型糖尿病患者肾功能减退或出现白蛋白尿时,血压≥130/80 mm Hg增加CAS危险;患者血压≥130/80 mm Hg时,肾功能减退或白蛋白尿增加CAS危险.多因素分析表明年龄、血压水平、eGFR水平、血压≥130/80 mm Hg、肾功能减退和白蛋白尿的发生均与CAS独立相关,而年龄、血压≥130/80 mm Hg、肾功能减退和白蛋白尿是CAS的独立危险因素.结论 肾功能减退、白蛋白尿以及血压升高与CAS既互相独立,又相互促进.

  13. Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey

    Directory of Open Access Journals (Sweden)

    Jae Hee Ahn

    2014-04-01

    Full Text Available BackgroundDiabetic nephropathy is a leading cause of end stage renal disease and is associated with an increased risk of cardiovascular mortality. It manifests as albuminuria or impaired glomerular filtration rate (GFR, and the prevalence of diabetic nephropathy varies with ethnicity. The prevalence of diabetic nephropathy and its determinants in Korean adults have not previously been studied at the national level. This cross-sectional study was undertaken to ascertain the prevalence and determinants of albuminuria and chronic kidney disease (CKD in Korean patients with diabetes.MethodsThe Korea National Health and Nutrition Examination Survey (KNHANES V, conducted in 2011, was used to define albuminuria (n=4,652, and the dataset of KNHANES IV-V (2008-2011 was used to define CKD (n=21,521. Selected samples were weighted to represent the entire civilian population in Korea. Albuminuria was defined as a spot urine albumin/creatinine ratio >30 mg/g. CKD was defined as a GFR <60 mL/min/1.73 m2.ResultsAmong subjects with diabetes, 26.7% had albuminuria, and 8.6% had CKD. Diabetes was associated with an approximate 2.5-fold increased risk of albuminuria, with virtually no difference between new-onset and previously diagnosed diabetes. Only systolic blood pressure was significantly associated with albuminuria, and old age, high serum triglyceride levels, and previous cardiovascular disease (CVD were related with CKD in subjects with diabetes.ConclusionKorean subjects with diabetes had a higher prevalence of albuminuria and CKD than those without diabetes. Blood pressure was associated with albuminuria, and age, triglyceride level, and previous CVD were independent determinants of CKD in subjects with diabetes.

  14. Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Sandholm, Niina; Forsblom, Carol; Mäkinen, Ville-Petteri;

    2014-01-01

    gene were strongly associated with albuminuria (p < 5 × 10(-8)). In the replication group, a nominally significant association (p = 0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48...... killer cell mediated immunity processes. CONCLUSIONS/INTERPRETATION: This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes....

  15. AT2R Agonist, Compound 21, Is Reno-Protective Against Type 1 Diabetic Nephropathy

    DEFF Research Database (Denmark)

    Koulis, Christine; Chow, Bryna S M; McKelvey, Maria;

    2015-01-01

    model of type 1 diabetic nephropathy. Compound 21 treatment significantly attenuated diabetes mellitus-induced elevated levels of cystatin C, albuminuria, mesangial expansion, and glomerulosclerosis in diabetic mice. Moreover, Compound 21 markedly inhibited the expression of various proteins implicated...

  16. Linking adiponectin to proteinuria

    OpenAIRE

    Ahima, Rexford S.

    2008-01-01

    Obesity predisposes toward renal disease independently of diabetes and hypertension. In this issue of the JCI, Sharma and colleagues assessed the role of adiponectin, an adipose-derived hormone, in the pathogenesis of albuminuria (see the related article beginning on page 1645). Obese African Americans had reduced adiponectin levels associated with albuminuria. Adiponectin deficiency in mice induced oxidative stress, fusion of podocyte foot processes in the kidney glomerulus, and urinary albu...

  17. Elevated Systemic Neutrophil Count Is Associated with Diabetic Macroalbuminuria among Elderly Chinese

    Directory of Open Access Journals (Sweden)

    Min Yang

    2015-01-01

    Full Text Available Background. This study investigated an association between systemic absolute neutrophil count (ANC and albuminuria in elderly Chinese people. Methods. A cross-sectional study was conducted on 2265 participants attending a routine medical examination in Minhang District as part of a Platform of Chronic Disease program. Their drug history, waist circumference, height, blood pressure, fasting blood glucose, ANC, and urine albumin levels were recorded. This study conformed to the requirements of the STROBE statement. Results. Of the 2265 subjects, 1254 (55.4% were diabetic and 641 (28.3% had albuminuria. The mean ANC of patients with diabetes comorbid with macroalbuminuria was significantly higher than that of both the nondiabetic patients and patients with diabetes with lower levels of albuminuria; the latter 2 groups had statistically similar ANC. ANC significantly and positively correlated with levels of urine albumin. Based on multivariate analysis, with each 109/L increase in ANC, the increase in rates of macroalbuminuria was significant but not in rates of albuminuria positivity. Based on areas under the receiver operating characteristic curve, ANC was the strongest factor predicting macroalbuminuria. Conclusions. Elevated ANC was associated with macroalbuminuria in diabetes, indicating that neutrophil-mediated inflammation may be involved in the exacerbation of albuminuria.

  18. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut;

    2005-01-01

    likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use. CONCLUSIONS: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux......CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present......, possibly explaining increased intimal lipoprotein accumulation and thus atherosclerosis. DESIGN: The study was cross-sectional and was performed in 1999-2002. SETTING: The study took place in the referral center. PATIENTS: The patients included 60 with diabetes mellitus (27 with type 1 diabetes and 33...

  19. The renoprotective effects of sulodexide

    Directory of Open Access Journals (Sweden)

    Olde Engberink RH

    2016-03-01

    Full Text Available Rik HG Olde Engberink, Liffert Vogt Department of Internal Medicine, Section of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsIn their meta-analysis, Li et al1 reported a renoprotective benefit of sulodexide in patients with diabetic nephropathy. This was the first meta-analysis to evaluate the potential anti-albuminuric effects of sulodexide in such patients. Albuminuria reduction with renin–angiotensin–aldosterone system inhibitors is known to beneficially affect renal outcome and represents, together with blood pressure control, the cornerstone of diabetic nephropathy treatment.2–6 As (residual albuminuria is closely related with renal outcome and the reduction in albuminuria is linearly correlated with renoprotection, we need additional measures to reduce the burden of diabetic nephropathy.7 The meta-analysis of Li et al1 therefore addresses a very relevant topic.View original paper by Li and colleagues. 

  20. Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester

    DEFF Research Database (Denmark)

    Damm, Peter; Mersebach, Henriette; Råstam, Jacob;

    2014-01-01

    . Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p=0.012). In the third trimester, elevated HbA1c, ≥ 1 plasma glucose (PG) measurement >11 mmol/L (198 mg/dL) and %PG values outside 3.9-7.0 mmol/L (70-126 mg/dL) were significant predictors of poor...... late-pregnancy outcomes (all pA1c, high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes....

  1. Renal disease in adult Nigerians with sickle cell anemia: A report of prevalence, clinical features and risk factors

    Directory of Open Access Journals (Sweden)

    R A Bolarinwa

    2012-01-01

    Full Text Available Renal abnormalities in adult Nigerians with sickle cell anemia (SCA have not been extensively studied. To determine the prevalence, pattern and the associated risk factors of renal disease, 72 subjects with SCA from two centers in the southwestern Nigeria were investigated. Socio-demographic data, body mass index and clinical findings were documented. The urine analysis, serum bio-chemistry, hemogram and renal factors attributable to SCA were determined. Presence of albuminuria of at least 1+ or microalbuminuria in those negative with dipstick; and the estimated glomerular filtration rate (eGFR using the Cockcroft-Gault formula categorized subjects to various stages of chronic kidney disease (CKD. Subjects with and without albuminuria were compared to determine the relative risk associated with renal disease. Four (5.6% subjects had macro-albuminuria, while 32 (44.4% had micro-albuminuria and 30 (41.7% had hemoglobinuria. In the subjects with albuminuria, age, hematocrit, systolic blood pressure, serum creatinine, urea and creatinine clearance were numerically higher while the eGFR was numerically lower. There was no significant difference in the clinical parameters studied in the two groups of subjects. The diastolic blood pressure was significantly higher in the albuminuric group. Based on eGFR, 22 (30.6% subjects had hyperfiltration (GFR > 140 mL/min/1.73 m2, of whom 36.4% had albuminuria, 18 (25.0% had stage 1 CKD, 30 (41.7% had stage 2 CKD and two (2.7% subjects had stage 3 CKD with albuminuria. None had stage 4 and 5 CKD. We conclude that renal abnormalities, importantly albuminuria, is common in adult Nigerians with SCA and the pattern and incidence are similar to those reported from other parts of the world. Regular blood pressure monitoring, early diagnosis and active intervention are advocated to delay progression to end-stage kidney disease in view of poor outcomes of renal replacement therapy in SCA patients with nephropathy.

  2. Effect of LDL cholesterol and treatment with losartan on end-stage renal disease in the RENAAL study

    DEFF Research Database (Denmark)

    Tershakovec, A.M.; Keane, W.F.; Zhang, Z.;

    2008-01-01

    levels and treatment with losartan on end-stage renal disease (ESRD). Lipid levels and albuminuria measurements were obtained at baseline and at year 1 in a post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, which compared the effects...... of losartan- versus placebo-based antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria Udgivelsesdato: 2008/3...

  3. Tubular and glomerular injury in diabetes and the impact of ACE inhibition

    DEFF Research Database (Denmark)

    Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise;

    2009-01-01

    OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We......, 46, and 40% with increasing doses of lisinopril (NS). CONCLUSIONS: An early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular...

  4. Dual RAS Therapy Not on Target, but Fully Alive

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; de Zeeuw, D.

    2010-01-01

    Inhibitors of the renin-angiotensin system (RAS) form a cornerstone in the treatment of kidney disease. These drugs lower blood pressure and albuminuria, and afford renal protection. Dual therapy with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker have been shown to be m

  5. Microalbuminuria and Risk of Venous Thromboembolism

    NARCIS (Netherlands)

    Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Veeger, Nic J. G. M.; Matthews, Abigail G.; Navis, Gerjan; Hillege, Hans L.; van der Meer, Jan

    2009-01-01

    Context Microalbuminuria (albuminuria 30-300 mg per 24-hour urine collection) is a well-known risk marker for arterial thromboembolism. It is assumed that microalbuminuria reflects generalized endothelial dysfunction. Hence, microalbuminuria may also predispose for venous thromboembolism (VTE). Obje

  6. Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; van der Harst, Pim; van Roon, Arie M.; Hillege, Hans L.; de Jong, Paul E.; Gans, Reinold O. B.; Smit, Andries J.; van Gilst, Wiek H.

    2008-01-01

    The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matchi

  7. Tubular and Glomerular Injury in Diabetes and the Impact of ACE Inhibition

    OpenAIRE

    Nielsen, Stine E.; Sugaya, Takeshi; Tarnow, Lise; Lajer, Maria; Schjoedt, Katrine J.; Astrup, Anne Sofie; Baba, Tsuneharu; Parving, Hans-Henrik; Rossing, Peter

    2009-01-01

    OBJECTIVE We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary–liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied Caucasians with type 1 diabetes: 58 with normoalbuminuria (urinary albumin

  8. Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

    NARCIS (Netherlands)

    Schanstra, Joost P.; Zuerbig, Petra; Alkhalaf, Alaa; Argiles, Angel; Bakker, Stephan J. L.; Beige, Joachim; Bilo, Henk J. G.; Chatzikyrkou, Christos; Dakna, Mohammed; Dawson, Jesse; Delles, Christian; Haller, Hermann; Haubitz, Marion; Husi, Holger; Jankowski, Joachim; Jerums, George; Kleefstra, Nanne; Kuznetsova, Tatiana; Maahs, David M.; Menne, Jan; Mullen, William; Ortiz, Alberto; Persson, Frederik; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Siwy, Justyna; Snell-Bergeon, Janet; Spasovski, Goce; Staessen, Jan A.; Vlahou, Antonia; Mischak, Harald; Vanholder, Raymond

    2015-01-01

    Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individu

  9. General pripciples, instruments and adaptations

    International Nuclear Information System (INIS)

    Experience of using roentgenoendovascular occlusion (REO) of vessels in clinical medicine have been analysed. Literary data are presented, experience in closure of vessel aneurysm, blocking of pathological arteriovenous anastomoses, functional exclusion of kidney at chronic renal insufficiency with hypertension and albuminuria, before kidney transplantation, functional splenectomy at hematologic diseases and hypersplenism and also of adducting arteries aimed at artificial ischemisation of neoplasms, is presented

  10. Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Smidt, U M;

    1983-01-01

    in arterial blood pressure to a hypertensive level is an early feature; 43% of the patients had diastolic blood pressure greater than 100 mm Hg. Early and aggressive antihypertensive treatment reduces both albuminuria and the rate of decline in GFR in young patients with diabetic nephropathy....

  11. Chronic kidney disease : Defining clinical cut-offs for albumin:creatinine ratio

    NARCIS (Netherlands)

    Bakker, Stephan J L

    2013-01-01

    Albuminuria is rapidly gaining recognition as a marker of the presence and of the progression of chronic kidney disease (CKD). In a new study, Naresh et al. attempt to define cut-off values for percentage change in urinary albumin:creatinine ratio that reflect changes in CKD status rather than rando

  12. Rationale, Design, and Baseline Characteristics of ARTS-DN : A Randomized Study to Assess the Safety and Efficacy of Finerenone in Patients with Type 2 Diabetes Mellitus and a Clinical Diagnosis of Diabetic Nephropathy

    NARCIS (Netherlands)

    Ruilope, Luis M.; Agarwal, Rajiv; Chan, Juliana C.; Cooper, Mark E.; Gansevoort, Ron T.; Haller, Hermann; Remuzzi, Giuseppe; Rossing, Peter; Schmieder, Roland E.; Nowack, Christina; Ferreira, Anna C.; Pieper, Alexander; Kimmeskamp-Kirschbaum, Nina; Bakris, George L.

    2014-01-01

    Background/Aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, random

  13. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, Peter; Tarnow, Lise; Vedel, Pernille;

    2004-01-01

    Intervention studies in microalbuminuric type 2 diabetic patients have demonstrated that it is possible to avoid progression to overt diabetic nephropathy and even to achieve regression to normoalbuminuria. However, the long-term impact of stabilization/regression in albuminuria on decline in glo...... in glomerular filtration rate (GFR) has not been established....

  14. Effects of Bariatric Surgery on Renal Function in Obese Patients: A Systematic Review and Meta Analysis

    Science.gov (United States)

    Ye, Zhibin; Di, Jianzhong; Han, Xiaodong; Zhang, Hongwei; Liu, Weijie; Ren, Qinggui; Zhang, Pin

    2016-01-01

    Background Obesity is an independent risk factor of development and progression of chronic kidney disease (CKD). Data on the benefits of bariatric surgery in obese patients with impaired kidney function have been conflicting. Objective To explore whether there is improvement in glomerular filtration rate (GFR), proteinuria or albuminuria after bariatric surgery. Methods We comprehensively searched the databases of MEDLINE, Embase, web of science and Cochrane for randomized, controlled trials and observational studies that examined bariatric surgery in obese subjects with impaired kidney function. Outcomes included the pre- and post-bariatric surgery GFR, proteinuria and albuminuria. In obese patients with hyperfiltration, we draw conclusions from studies using measured GFR (inulin or iothalamate clearance) unadjusted for BSA only. Study quality was evaluated using the Newcastle-Ottawa Scale. Results 32 observational studies met our inclusion criteria, and 30 studies were included in the meta-analysis. No matter in dichotomous data or in dichotomous data, there were statistically significant reduction in hyperfiltration, albuminuria and proteinuria after bariatric surgery. Limitations The main limitation of this meta-analysis is the lack of randomized controlled trials (RCTs). Another limitation is the lack of long-term follow-up. Conclusions Bariatric surgery could prevent further decline in renal function by reducing proteinuria, albuminuria and improving glomerular hyperfiltration in obese patients with impaired renal function. However, whether bariatric surgery reverses CKD or delays ESRD progression is still in question, large, randomized prospective studies with a longer follow-up are needed. PMID:27701452

  15. Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats

    DEFF Research Database (Denmark)

    Castoldi, Giovanna; di Gioia, Cira Rt; Bombardi, Camila;

    2014-01-01

    Aim of the study was to evaluate the effect of compound 21 (C21), selective AT2 receptor agonist, in diabetic nephropathy and the potential additive effect of C21, when associated to losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The ...

  16. Plasma Vasoprotective Eicosanoid Concentrations in Healthy Greyhounds and Non‐Greyhound Dogs

    OpenAIRE

    Martinez, J.T.; Rogers, L.K.; Kellogg, C.; Iazbik, M.C.; Couto, C.G.; Pressler, B.M.; Hoepf, T.M.; Radin, M.J.

    2016-01-01

    Background Hypertension and albuminuria often coexist in Greyhounds, suggesting generalized vascular dysfunction that could contribute to the development of a variety of diseases in this breed. Eicosanoid metabolites of arachidonic acid (AA) mediate endothelial function, vascular reactivity, and proteinuria in humans and in rodent models. Hypothesis The eicosanoid profile of Greyhounds is shifted toward metabolites that promote vascular dysfunction, hypertension, and proteinuria. Animals Heal...

  17. Solitary functioning kidney in children--a follow-up study

    NARCIS (Netherlands)

    Kolvek, Gabriel; Podracka, Ludmila; Rosenberger, Jaroslav; Stewart, Roy E.; van Dijk, Jitse P.; Reijneveld, Sijmen A.

    2014-01-01

    BACKGROUND/AIMS: This study aims to assess the cumulative incidence of elevated albuminuria, hypertension and decreased estimated glomerular filtration rate (eGFR) to identify possible renal injury in children with SFK. METHODS: Forty-two children with SFK (23 boys; 27 congenital) were included in a

  18. Effectiveness of Angiotensin II Receptor Antagonists in a Cohort of Dutch Patients With Type 2 Diabetes Mellitus (ZODIAC-14)

    NARCIS (Netherlands)

    van Hateren, Kornelis J. J.; Landman, Gijs W. D.; Groenier, Klaas H.; Bilo, Henk J. G.; Kleefstra, Nanne

    2015-01-01

    OBJECTIVE: There is limited evidence with respect to the between-group effects of various angiotensin receptor blockers (ARBs) on blood pressure and albuminuria in patients with type 2 diabetes mellitus. Therefore, we aimed to investigate the effects of differing ARBs on systolic blood pressure (SBP

  19. Changes of serum or urine type IV collagen concentrations and GFR in DM2 patients complicated with nephropathy

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of serum or urinary, type IV collagen concentration and GFR in patients with diabetic nephropathy (DN). Methods: Serum or urine type IV collagen concentrations (with RIA) and CFR (with SPECT) were determined in 136 DM2 patients with various degrees of albuminuria as well as in 30 controls. Results: Both the serum and urine type IV collagen concentrations were significantly higher in the diabetic patients than those in the controls, and the levels increased continuously as the renal involvement progressed (albuminuria from < 20 μg/min → 200 μg/min). The elevation of serum or urinary, type IV collagen occurred early, even before the increase of albuminuria. The CFR at this early stage was paradoxically higher than normal (135.6±41.4ml/min). Later, with progression of nephropathy, the albuminuria and serum/urine type IV collagen contents increased continuously but the CFR decreased to very low level. Successful control of blood sugar might reverse the increase of type IV collagen to certain degree. Conclusion: Determination of serum/urinary type IV collagen levels might be useful for early diagnosis and assessment of severity of the nephropathy complicating DM2. (authors)

  20. Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers

    DEFF Research Database (Denmark)

    Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A;

    2016-01-01

    , atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30...

  1. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension : a meta-analysis

    NARCIS (Netherlands)

    Mahmoodi, Bakhtawar K.; Matsushita, Kunihiro; Woodward, Mark; Blankestijn, Peter J.; Cirillo, Massimo; Ohkubo, Takayoshi; Rossing, Peter; Sarnak, Mark J.; Stengel, Benedicte; Yamagishi, Kazumasa; Yamashita, Kentaro; Zhang, Luxia; Coresh, Josef; de Jong, Paul E.; Astor, Brad C.

    2012-01-01

    Background Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive

  2. Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in type 1 diabetic patients with elevated urinary albumin excretion

    NARCIS (Netherlands)

    Blaauwwiekel, EE; Beusekamp, BJ; Sluiter, WJ; Hoogenberg, K; Dullaart, RPF

    1998-01-01

    The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 mu g min(-1). Apo E genotype was characterized by polymerase chai

  3. Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

    Directory of Open Access Journals (Sweden)

    Coll-de-Tuero Gabriel

    2012-08-01

    Full Text Available Abstract Background Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM. Methods Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke. Variables of renal function were defined as follows: 1 Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2 Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3 Kidney disease (KD: glomerular filtration rate according to Modification of Diet in Renal Disease 2 and/or the presence of albuminuria, 4 Renal impairment (RI: glomerular filtration rate 2, 5 Nonalbuminuric RI: glomerular filtration rate 2 without albuminuria and, 5 Diabetic nephropathy (DN: macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN. The prevalence of albuminuria without RI (13.5% and nonalbuminuric RI (14.7% was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86–2.59, microvascular disease (OR 2.14; CI 95% 1.8–2.54 and insulin treatment (OR 1.82; CI 95% 1.39–2.38, and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80–0.91. Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21–0.35, duration of diabetes (OR 0.94 per year; CI 95% 0.91–0.97 and directly associated with HbA1c (OR 1.19 for every

  4. Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

    Science.gov (United States)

    Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

    2016-01-01

    Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

  5. ACEI/ARB underused in patients with type 2 diabetes in Chinese population (CCMR-3B study.

    Directory of Open Access Journals (Sweden)

    Qionghong Xie

    Full Text Available In patients with diabetic kidney disease, it is well documented that RAS blockade is associated with an improved outcome. This observational, multicenter study examined the "real-world" use of ACEI/ARB in patients with type 2 diabetes (T2DM in China.Data from the China Cardiometabolic Registries on blood pressure, blood lipid and blood glucose in Chinese T2DM patients (CCMR-3B were used for the present study. Consecutive outpatients with T2DM for more than 6 months were recruited to this non-interventional, observational, cross-sectional study. Albuminuria was defined as urine albumin creatinine ratio (ACR ≥ 30 mg/g.A total of 25,454 outpatients with T2DM from 6 regions in China were enrolled, 47.0% were male, and 59.8% had hypertension. ACR was measured in 6,383 of these patients and 3,231 of them ≥ 30 mg/L. Among patients with hypertension, 73.0% were on antihypertensives, and 39.7% used ACEI/ARB. Of the 2,157 patients with hypertension and albuminuria, only 48.3% used ACEI/ARB. Among the non-hypertensive patients with albuminuria, ACEI/ARB usage was < 1%. Multivariate analysis revealed that comorbidities, region, hospital tier, physician specialty and patient's educational level were associated with ACEI/ARB use.In T2DM with hypertension and albuminuria in China, more than half of them were not treated with ACEI/ARB. This real world evidence suggests that the current treatment for patients with diabetes coexisting with hypertension and albuminuria in China is sub-optimal.

  6. Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population

    Institute of Scientific and Technical Information of China (English)

    LIU Dong-wei; WAN Jia; LIU Zhang-suo; WANG Pei; CHENG Gen-yang; SHI Xue-zhong

    2013-01-01

    Background Dyslipidemia,a well-known risk factor for cardiovascular disease,is common in patients with kidney disease.Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases,but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown.Thus,we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD.Methods A total of 4779 middle-aged and elderly participants participated in this study.Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults.Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR,<60 ml.min-1.1.73 m-2).Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR.Results Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs.6.1%,P=-0.001; 4.0% vs.2.4%,P=-0.028,respectively).Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08-2.07 and OR 1.53; 95% CI 1.13-2.09,respectively).The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95% CI 1.03-2.65).As the number of dyslipidemia components increased,so did the OR of CKD:0.87 (95% CI 0.65-1.15),1.29 (95% CI,0.83-2.01),and 7.87 (95% CI,3.75-16.50) for albuminuria,and 0.38 (95% CI 0.21-0.69),1.92 (95% CI 1.14-3.25),and 5.85 (95% CI 2.36-14.51)for reduced eGFR,respectively.Conclusions Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population.Hypercholesterolemia plays an important role in reducing total eGFR.Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.

  7. Effects of long-term antihypertensive treatment on kidney function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Andersen, A R; Hommel, E;

    1985-01-01

    The purpose of our prospective study was to evaluate the long-term effect of aggressive antihypertensive treatment on glomerular filtration rate and albuminuria in young female and male patients with insulin-dependent diabetes mellitus with diabetic nephropathy and blood pressure greater than 90 mm...... 140/96 +/- 4/1 to 150/100 +/- 3/2 mm Hg; albuminuria increased from 1517 +/- 502 to 1911 +/- 120 micrograms/min; and glomerular filtration rate decreased by a mean of 0.84 +/- 0.17 ml/min/mo in the untreated group. Antihypertensive treatment induced blood pressure reduction 151/100 +/- 3/2 to 131......). All patients except one had diabetic retinopathy. Glomerular filtration rate was measured after a single intravenous injection of 51Cr-labeled ethylenediaminetetraacetic acid. Urinary albumin concentration was determined with a radial immunodiffusion method. The investigations were performed two...

  8. Advanced oxidation protein products decrease expression of nephrin and podocin in podocytes via ROS-dependent activation of p38 MAPK

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin.The expression of glomerular podocyte slit diaphragm(PSD)-associated proteins,nephrin and podocin,was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs.Chronic inhibi-tion of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats.This suggested that accumulation of AOPPs promotes proteinuria,possibly via down-regulating the expression of PSD-associated proteins.

  9. Segmental tubular sodium reabsorption in type 1 diabetes

    DEFF Research Database (Denmark)

    Dieperink, H; Eshøj, O; Leyssac, P P;

    1993-01-01

    Segmental tubular sodium reabsorption in Type 1 (insulin-dependent) diabetes was measured in 36 patients in a cross-sectional study including one group (n = 13) without significant albuminuria (UalbV 1), one group (n = 16) with albuminuria in the range from 30 to 300 mg 24 h-1......, and a group (n = 7) with nephropathy (UalbV > 300 mg 24 h-1). Lithium clearance was used to measure end proximal delivery. From end proximal delivery, 51Cr-EDTA clearance (GFR) and sodium clearance, segmental tubular reabsorption was calculated. For all patients, GFR was directly correlated with end proximal...... delivery (r = 0.62, p 1, the direct correlation between GFR and end proximal delivery was also significant (r = 0.77, p

  10. A low-protein diet restricts albumin synthesis in nephrotic rats.

    OpenAIRE

    Kaysen, G A; Jones, H.; Martin, V.; Hutchison, F N

    1989-01-01

    High-protein diets increase albumin synthesis in rats with Heymann nephritis but albuminuria increases also, causing serum albumin concentration to be suppressed further than in nephrotic animals eating a low-protein diet. Experiments were designed to determine whether dietary protein augmentation directly stimulates albumin synthesis, or whether instead increased albumin synthesis is triggered by the decrease in serum albumin concentration. Evidence is presented that dietary protein augmenta...

  11. Microalbuminuria: a Cardiovascular Risk Factor

    OpenAIRE

    ERCAN, Ertuğrul

    2010-01-01

    Albumin is a protein which is charged negatively. By correcting for the daily excretion of creatinine, the albumin creatinin ratio implicates the daily excretion of albumin in spot urine. Albuminuria is a cardiovascular risk factor in patients with diabetes, hypertension, and the general population. Urinary albumin excretion is independently associated with an increased risk of cardiovascular events, even after adjustment for risk factors. Risk has been shown to increase continuously with inc...

  12. Association of Periodontitis With Urinary Albumin Excretion in Korean Adults With Diabetes: The 2012 Korea National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Han, Kyungdo; Nam, Ga Eun; Kim, Do Hoon; Park, Jun-Beom; Ko, Youngkyung; Roh, Yong Kyun; Cho, Kyung Hwan; Park, Yong Gyu

    2015-10-01

    Albuminuria and periodontitis are both commonly associated with systemic inflammation. However, the association between urinary albumin excretion (UAE) and periodontitis in patients with type 2 diabetes has not been fully investigated. This study aimed to investigate the association between UAE and periodontitis in Korean adults with type 2 diabetes.This study performed a cross-sectional analysis and used hierarchical multivariable logistic regression analysis models. Data from the 2012 Korean National Health and Nutrition Examination Survey were analyzed. A total of 547 patients, with type 2 diabetes without renal impairment, were included in this study. UAE was assessed using the urinary albumin to creatinine ratio (UACR). A community periodontal index greater than or equal to code 3 was used to define periodontitis.The risk of periodontitis tended to increase as UACR increased even after adjustment for potential confounders (P for trend in the odds ratios = 0.05 in model 1; 0.02 in model 2; and 0.01 in model 3). In a subgroup analysis, the prevalence of periodontitis was significantly higher in the patients with albuminuria (UACR >30 mg/g) than in those without albuminuria among patients younger than 65 years (P = 0.03), those with newly diagnosed diabetes (P = 0.04), or those without obesity (P = .04).UAE was positively associated with the risk of periodontitis in Korean adults with type 2 diabetes. In the patients who were younger, were newly diagnosed with diabetes, or had normal body mass index, individuals with albuminuria were more likely to have a higher prevalence of periodontitis. Early identification of periodontitis may be helpful in Korean diabetic adults with increased UAE.

  13. Tissue transglutaminase inhibition as treatment for diabetic glomerular scarring: it's good to be glueless.

    Science.gov (United States)

    Schelling, Jeffrey R

    2009-08-01

    Diabetic nephropathy is characterized by enhanced glomerular and tubulointerstitial deposition of extracellular matrix proteins, which are bound together by tissue transglutaminase (TG2). Huang et al. demonstrate that infusion of a novel TG2 inhibitor in diabetic rats prevented renal scarring and albuminuria and preserved glomerular filtration rate. These studies confirm the role of TG2 in the pathogenesis of diabetic nephropathy and add to an emerging literature that demonstrates that TG2 is an attractive therapeutic target for sclerosing kidney diseases.

  14. A susceptibility gene for kidney disease in an obese mouse model of type II diabetes maps to chromosome 8

    OpenAIRE

    Chua, Streamson; Li, Yifu; Liu, Shun Mei; Liu, Ruijie; Chan, Ka Tak; Martino, Jeremiah; Zheng, Zongyu; Susztak, Katalin; D'Agati, Vivette D.; Gharavi, Ali G.

    2010-01-01

    Most mouse models of diabetes do not fully reproduce features of human diabetic nephropathy, limiting their utility in inferring mechanisms of human disease. Here we performed detailed phenotypic and genetic characterization of leptin-receptor (Lepr) deficient mice on the FVB/NJ background (FVBdb/db), an obese model of type II diabetes, to determine their suitability to model human diabetic nephropathy. These mice have sustained hyperglycemia, significant albuminuria and characteristic diabet...

  15. Association of Serum Leptin Levels With Progression of Diabetic Kidney Disease in Patients With Type 2 Diabetes

    OpenAIRE

    Hanai, Ko; Babazono, Tetsuya; Mugishima, Michino; Yoshida, Naoshi; Nyumura, Izumi; Toya, Kiwako; Bouchi, Ryotaro; Tanaka, Nobue; Uchigata, Yasuko

    2011-01-01

    OBJECTIVE To clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria. RESULTS Patients with low ...

  16. Manifestation of renal disease in obesity: pathophysiology of obesity-related dysfunction of the kidney

    OpenAIRE

    Weinrauch, Larry

    2009-01-01

    John A D’Elia, Bijan Roshan, Manish Maski, Larry A WeinrauchJoslin Diabetes Center, Renal Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, MassachusettsAbstract: Albuminuria in individuals whose body mass index exceeds 40 kg/m2 is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte) distortion. Obstructive sleep apnea magnifies glomerular...

  17. Association between urinary sodium, creatinine, albumin, and long-term survival in chronic kidney disease.

    Science.gov (United States)

    McQuarrie, Emily P; Traynor, Jamie P; Taylor, Alison H; Freel, E Marie; Fox, Jonathan G; Jardine, Alan G; Mark, Patrick B

    2014-07-01

    Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium (UNa) excretion and UNa to creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adult patients attending a renal clinic who had ≥1 24-hour UNa measurement were identified. Twenty-four-hour UNa measures were collected and UNa to creatinine ratio calculated. Time to renal replacement therapy or death was recorded. Four hundred twenty-three patients were identified with mean estimated glomerular filtration rate of 48 mL/min per 1.73 m(2). Ninety patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8 mL/min per 1.73 m(2) per year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher UNa excretion and UNa to creatinine ratio, but the association with these parameters and poor outcome was not independent of renal function, age, and albuminuria. When stratified by albuminuria, UNa to creatinine ratio was a significant cumulative additional risk for mortality, even in patients with low-level albuminuria. There was no association between low UNa and risk, as observed in some studies. This study demonstrates an association between UNa excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria, and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease, but additional study is required to determine the target sodium intake. PMID:24732890

  18. KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods

    OpenAIRE

    Oh, Kook-Hwan; Park, Sue Kyung; Park, Hayne Cho; Chin, Ho Jun; Chae, Dong Wan; Choi, Kyu Hun; Han, Seung Hyeok; Yoo, Tae Hyun; Lee, Kyubeck; Kim, Yong-Soo; Chung, Wookyung; Hwang, Young-Hwan; Kim, Soo Wan; Kim, Yeong Hoon; Kang, Sun Woo

    2014-01-01

    Background The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis). Methods/Design Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adult...

  19. Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney Disease

    OpenAIRE

    You, Y-H; Quach, T; Saito, R; Pham, J; Sharma, K

    2016-01-01

    The NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease (DKD). However, a mechanistic understanding of the downstream effects of NOX4 remains to be established. We report that podocyte-specific induction of NOX4 in vivo was sufficient to recapitulate the characteristic glomerular changes noted with DKD, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, albuminuria, and podocyte dropout. Intervention with a NOX1/...

  20. Fenofibrate Improves Renal Lipotoxicity through Activation of AMPK-PGC-1α in db/db Mice

    OpenAIRE

    Yu Ah Hong; Ji Hee Lim; Min Young Kim; Tae Woo Kim; Yaeni Kim; Keun Suk Yang; Hoon Suk Park; Sun Ryoung Choi; Sungjin Chung; Hyung Wook Kim; Hye Won Kim; Bum Soon Choi; Yoon Sik Chang; Cheol Whee Park

    2014-01-01

    Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited ac...

  1. Mammalian Target of Rapamycin Regulates Nox4-Mediated Podocyte Depletion in Diabetic Renal Injury

    OpenAIRE

    Eid, Assaad A.; Ford, Bridget M.; Bhandary, Basant; de Cassia Cavaglieri, Rita; Block, Karen; Barnes, Jeffrey L.; Gorin, Yves; Choudhury, Goutam Ghosh; Abboud, Hanna E.

    2013-01-01

    Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Pharmacological doses of the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduce albuminuria in diabetes. We explored the hypothesis that mTOR mediates podocyte injury in diabetes. High glucose (HG) induces apoptosis of podocytes, inhibits AMP-activated protein kinase (AMPK) activation, inactivates tuberin, and activates mTOR. HG also increases the levels of Nox4 an...

  2. A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

    Institute of Scientific and Technical Information of China (English)

    GENG Li; GU Ming-jun; LIU Zhi-min; FAN Cheng-hui

    2001-01-01

    To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3.1 software.Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h [-100.748 to-54.256], -5.002 mmHg [-9.630 to 0.685], -2.949mmHg [-4.005 to 1.892], -4.284 mmHg [-5.444 to 3.123] respectively. Using clinical albuminuria as the end-point. The pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure, diastolic blood pressure or mean arterial blood pressure. Conclusion:ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

  3. Nephrotic Syndrome and The TCM Treatment

    Institute of Scientific and Technical Information of China (English)

    王巍; 王淑琴

    2004-01-01

    @@ Nephrotic syndrome is a symptom complex characterized by severe albuminuria (+++ to ++++ in qualitative test and > 3.5 g/L in quantitative test),hypoproteinemia (< 3 g/L), edema and hyperlipemia(apparently increased plasma cholesterol and triglyceride and increased low density lipoprotein,LDL) due to abnormally increased permeability of glomerular capillary wall against plasma proteins.There may be lipoiduria with normal or abnormal level of high density lipoprotein (HDL).

  4. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Directory of Open Access Journals (Sweden)

    Sarika Kapoor

    Full Text Available The sodium-glucose-cotransporter-2 (SGLT2 inhibitor dapagliflozin (DAPA induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD, we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group. Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d. DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  5. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats.

    Science.gov (United States)

    Kapoor, Sarika; Rodriguez, Daniel; Riwanto, Meliana; Edenhofer, Ilka; Segerer, Stephan; Mitchell, Katharyn; Wüthrich, Rudolf P

    2015-01-01

    The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.

  6. The emerging concept of chronic kidney disease without clinical proteinuria in diabetic patients.

    Science.gov (United States)

    Halimi, J M

    2012-10-01

    The natural history of diabetic nephropathy was defined in the 1980s on the basis of longitudinal studies undertaken in patients with type 1 and type 2 diabetes. However, an increasing number of studies have indicated that certain diabetic patients do not present with the same evolution as was then defined: for example, some often have significant initial deterioration of glomerular filtration rate whereas, in others, microalbuminuria is reduced spontaneously. Chronic kidney disease (CKD) may be accompanied, rather than preceded, by macroalbuminuria, or it may develop in patients with microalbuminuria or even in those with albuminuria levels that revert to normal. CKD can also develop in patients whose albuminuria levels remain normal. Progression to macroalbuminuria is, in fact, less frequent than regression to normoalbuminuria or no change in microalbuminuria status in diabetic patients with microalbuminuria, especially in type 1 diabetes. Some experience progressive deterioration of renal function due to diabetes without developing significant proteinuria: this is seen fairly frequently and can affect 50% of patients with renal insufficiency. Such cases are more often older patients treated with renin-angiotensin system blockers who usually have a history of cardiovascular disease. Evolution to end-stage renal disease is slower in this subgroup of patients, although histological analyses may show surprisingly advanced glomerular lesions. The main parameters of surveillance remain regular monitoring of glycaemia, and control of blood pressure and the evolution of initial albuminuria levels. Nevertheless, why some patients exhibit conventional diabetic nephropathy while others have slower declines in renal function associated with normal albuminuria levels or microalbuminuria is unclear. It is hoped that the new pathological classification of diabetic nephropathy will help in our understanding of these discrepancies.

  7. The renoprotective effects of sulodexide

    OpenAIRE

    Olde Engberink RH; Vogt L

    2016-01-01

    Rik HG Olde Engberink, Liffert Vogt Department of Internal Medicine, Section of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, the NetherlandsIn their meta-analysis, Li et al1 reported a renoprotective benefit of sulodexide in patients with diabetic nephropathy. This was the first meta-analysis to evaluate the potential anti-albuminuric effects of sulodexide in such patients. Albuminuria reduction with renin–angiotensin–aldosterone system inhibit...

  8. T cells and macrophages in Trypanosoma brucei-related glomerulopathy.

    Science.gov (United States)

    van Velthuysen, M L; Mayen, A E; van Rooijen, N; Fleuren, G J; de Heer, E; Bruijn, J A

    1994-08-01

    In a previous study, susceptibility for Trypanosoma brucei-related glomerulopathy in mice was shown to be dependent on non-major histocompatibility complex genes. Glomerular disease in this model could not be explained by the production of autoantibodies alone. In order to analyze which part of the defense system, in addition to the B-cell compartment, is involved in the development of this infection-related glomerular disease, groups of athymic (BALB/c rnu/rnu), splenectomized, or macrophage-depleted BALB/c mice were inoculated with T. brucei parasites. Polyclonal B-cell activation, invariably observed in infected BALB/c mice, was absent in BALB/c rnu/rnu mice. Glomerular disease in athymic mice, however, as defined by albuminuria and deposition of immune complexes, was not different from that seen in euthymic infected BALB/c mice. Splenectomy prior to inoculation of parasites led to a decreased incidence of albuminuria in 40% of the animals, whereas splenectomy 21 days after inoculation reduced albuminuria significantly, suggesting a role for spleen cells in the induction of glomerular disease. After macrophage depletion with liposome-encapsulated dichlorodimethylene-diphosphonate, infected BALB/c mice developed significantly higher albuminuria levels for a period up to 2 weeks after depletion. Therefore, it was concluded that the development of T. brucei-related glomerular disease is independent of thymus-matured T cells, while the involvement of macrophages in the development of proteinuria is inhibitory rather than disease inducing. Spleen cells other than thymus-dependent T cells, B cells, and macrophages should be investigated for their role in the pathogenesis of this glomerulopathy. PMID:7913696

  9. Association between microalbuminuria and subclinical atherosclerosis evaluated by carotid artery intima-media in elderly patients with normal renal function

    OpenAIRE

    Kong XiangLei; Jia XiaoYan; Wei Yong; Cui MeiYu; Wang ZunSong; Tang LiJun; Li WenBin; Zhu ZhuXian; Chen Ping; Xu DongMei

    2012-01-01

    Abstract Background Moderate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT) and microalbuminuria in elderly patients with normal renal function. Methods Subjects were 272 elderly patients (age  ≥ 60 years) with normoalbuminuria (n = 238) and microalbuminuria (n = 34). Carotid IMT wa...

  10. Association between family members of dialysis patients and chronic kidney disease: a multicenter study in China

    Directory of Open Access Journals (Sweden)

    Kong Xianglei

    2013-01-01

    Full Text Available Abstract Background Family members of patients with end stage renal disease were reported to have an increased prevalence of chronic kidney disease (CKD. However, studies differentiated genetic and non-genetic family members are limited. We sought to investigate the prevalence of CKD among fist-degree relatives and spouses of dialysis patients in China. Methods Seventeen dialysis facilities from 4 cities of China including 1062 first-degree relatives and 450 spouses of dialysis patients were enrolled. Sex- and age- matched controls were randomly selected from a representative sample of general population in Beijing. CKD was defined as decreased estimated glomerular (eGFR 2 or albuminuria. Results The prevalence of eGFR less than 60 mL/min/1.73 m2, albuminuria and the overall prevalence of CKD in dialysis spouses were compared with their counterpart controls, which was 3.8% vs. 7.8% (P 2, albuminuria and the overall prevalence of CKD in dialysis relatives were also compared with their counterpart controls, which was 1.5% vs. 2.4% (P = 0.12, 14.4% vs. 8.4% (P  Conclusions The association between being family members of dialysis patients and presence of CKD is different between first-degree relatives and spouses. The underlying mechanisms deserve further investigation.

  11. Will the future lie in multitude? A critical appraisal of biomarker panel studies on prediction of diabetic kidney disease progression.

    Science.gov (United States)

    Schutte, Elise; Gansevoort, Ron T; Benner, Jacqueline; Lutgers, Helen L; Lambers Heerspink, Hiddo J

    2015-08-01

    Diabetic kidney disease is diagnosed and staged by albuminuria and estimated glomerular filtration rate. Although albuminuria has strong predictive power for renal function decline, there is still variability in the rate of renal disease progression across individuals that are not fully captured by the level of albuminuria. Therefore, research focuses on discovering and validating additional biomarkers that improve risk stratification for future renal function decline and end-stage renal disease in patients with diabetes, on top of established biomarkers. Most studies address the value of single biomarkers to predict progressive renal disease and aim to understand the mechanisms that underlie accelerated renal function decline. Since diabetic kidney disease is a disease encompassing several pathophysiological processes, a combination of biomarkers may be more likely to improve risk prediction than a single biomarker. In this review, we provide an overview of studies on the use of multiple biomarkers and biomarker panels, appraise their study design, discuss methodological pitfalls and make recommendations for future biomarker panel studies.

  12. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

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    Toshitaka Umemura

    2013-07-01

    Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

  13. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

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    Takahiko Kawamura

    2016-02-01

    Full Text Available Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR, albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

  14. Determining the Levels of Vitamin D and Parathyroid Hormone in Patients on Hemodialysis

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    Mihaylov R.

    2016-03-01

    Full Text Available Vitamin D deficiency is fequently observed in chronic kidney disease. We conducted this study to determine the concentration of the above-mentioned parameters and the correlation between them in order to optimize therapy with vitamin D in patients with end-stage renal disease (ESRD on hemodialysis. In 53 patients on hemodialysis due to ESRD, vitamin D [Calcidiol (25(OHD], parathyroid hormone (PTH, calcium, phosphorus, albuminuria, albumin:creatinine ratio (ACR and other parameters have been followed up. Analysis of the levels of vitamin D has been carried out by High Performance Liquid Chromatography (HPLC, the PTH is determined by the system Centaur XP, Siemens Diagnostic, Electro-chemiluminescence immunoassay (ECLIA, and for albumin in urine we used immunological method [Miltigent microalbumin assay (Abbott Laboratories Diagnostics. We found out deficiency and insufficiency of vitamin D in 56.6% and 37.7%, as well as average 4.5 times increase in the PTH, hyperphosphatemia, hypocalcemia, albuminuria (A2 or A3, over 10 times increase in the ACR, secondary hyperparathyroidism. We registered a negative correlation between vitamin D and PTH. We confirmed the increase in creatinine and cystatin C in the patients on hemodialysis. There are few literature data for patients on hemodialysis, however, regarding the extent of the vitamin deficiency and its relationship with PTH, albuminuria, calcium, phosphorus, etc. Our data have indicated that patients on hemodialysis due to ESRD are associated with high incidence of vitamin D insufficiency or deficiency.

  15. Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

    Science.gov (United States)

    Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

    2016-08-01

    The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients. PMID:27307060

  16. Coefficient of variation of R-R intervals in electrocardiogram is a sensitive marker of anemia induced by autonomic neuropathy in type 1 diabetes.

    Science.gov (United States)

    Saito, Takatoshi; Tojo, Katsuyoshi; Nishimura, Rimei; Kageyama, Shigeru; Tajima, Naoko

    2007-10-01

    The present study investigated the relationship between hemoglobin (Hb) levels and autonomic failure using a sensitive marker, coefficient of variation of R-R intervals in electrocardiogram (CVR-R) in order to clarify a cause of normocytic normochromic anemia in type 1 diabetic patients without overt nephropathy. We recruited 46 patients with type 1 diabetes and measured creatinine clearance (Ccr), HbA1c, albuminuria, Hb levels and CVR-R of all patients. In addition, the status of diabetic retinopathy and neuropathy were also evaluated. Serum erythropoietin (EPO), Fe, total iron binding capacity, lactate dehydrogenase, total bilirubin levels and number of reticulocytes and mean corpuscular volume were also measured to distinguish types of anemia. To survey the statistical correlation existing between Hb and body mass index (BMI), Ccr, HbA1c, albuminuria or retinopathy, multiple regression analysis was performed. Serum EPO, Fe, TIBC, LDH and TB levels and number of reticulocytes and MCV were within normal limits. Multiple regression analysis disclosed that HbA1c, nephropathy evaluated by albuminuria and Ccr, and retinopathy has no concern with Hb level. There is only significant relationship between Hb levels and CVR-R. Similar results were obtained even if we analyzed a group of male and female separately. We conclude that CVR-R has the strong relationship on anemia without overt nephropathy in type 1 diabetes, indicating that autonomic failure contributes on the progression of anemia via a poor response of EPO to anemia.

  17. Levels of Inflammatory Cytokines in Type 2 Diabetes Patients with Different Urinary Albumin Excretion Rates and Their Correlation with Clinical Variables

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    Fen-qin Chen

    2013-01-01

    Full Text Available Although the pathogenetic mechanism of DN has not been elucidated, an inflammatory mechanism has been suggested as a potential contributor. This study was designed to explore the relationship between low-grade inflammation and renal microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three groups according to UAE: a normal albuminuria group, a microalbuminuria group, and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP, TNF-α, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were measured in all subjects. Compared with the normal controls, levels of hs-CRP, TNF-α, uMCP-1, and SAA in T2DM patients were significantly higher. They were also elevated in the normal albuminuria group, P<0.05. Compared with the normal albuminuria group, levels of these inflammatory cytokines were significantly higher in the microalbuminuria and macroalbuminuria group, P<0.01. The macroalbuminuria group also showed higher levels than the microalbuminuria group, P<0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC. We noted no significance correlated with course, TG, or HDL-C. Only TNF-α; was positively correlated with HbA1c. This study revealed the importance of these inflammatory cytokines in DN pathogenesis. Further studies are needed to fully establish the potential of these cytokines as additional biomarkers for the development of DN.

  18. PHOSPHATE METABOLISM IN KIDNEY DONORS: A CROSS-SECTIONAL STUDY

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    Jayakumar Edathedathe

    2016-05-01

    Full Text Available AIM To study the changes in phosphate metabolism in kidney donors, to study the correlation of albuminuria, fractional excretion of phosphorus [FE Pi] and estimated glomerular filtration rate [eGFR] with fibroblast growth factor 23 [FGF 23] in kidney donors, to study the early tubule interstitial injury in the remnant kidney of donors by measuring urine transforming growth factor beta [TGF beta] levels. MATERIALS AND METHODS A cross-sectional study in which kidney donors with 1 year or more after donation were included. 69 kidney donors with a mean duration of 5.86 years after kidney donation were studied. Serum phosphate level, fractional excretion of phosphorus [FE Pi] and serum levels of parathyroid hormone were measured. Plasma levels of FGF 23 were measured by a second generation enzyme linked immune sorbent assay [ELISA]. Renal function was assessed by estimated glomerular filtration rate [eGFR] and degree of albuminuria. Urine levels of transforming growth factor beta [TGF beta] were measured by ELISA. A hypothesis that in kidney donors with reduced nephron number, the single nephron excretion of phosphorus will be increased to maintain normal phosphorus homeostasis and that this increase in single nephron phosphorus excretion may be mediated by FGF 23 was proposed. Testing of this hypothesis was done by studying the correlation between parameters of phosphorus metabolism, FGF 23 and the renal function of the donors. RESULTS The mean eGFR was 70.36 mL/min/1.73 m2 . 52.2% of donors had moderate increase in albuminuria [microalbuminuria], Serum phosphorus, fractional excretion of phosphorus and serum PTH levels were in the normal range. FGF 23 levels were in the normal reference range and showed no correlation with FE pi, eGFR or albuminuria, Urine TGF-beta levels were undetectable in all the donors. DISCUSSION Normal phosphorus homeostasis is maintained in kidney donors. There was no correlation between FE pi and FGF 23 levels. Kidney

  19. Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.

    Science.gov (United States)

    De Silva, Pallagae Mangala C S; Mohammed Abdul, Khaja Shameem; Eakanayake, Eakanayake M D V; Jayasinghe, Sudheera Sammanthi; Jayasumana, Channa; Asanthi, Hewa Bandulage; Perera, Hettiarachigae S D; Chaminda, Gamage G Tushara; Chandana, Ediriweera P S; Siribaddana, Sisira H

    2016-09-01

    Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury

  20. Astragaloside IV, a novel antioxidant, prevents glucose-induced podocyte apoptosis in vitro and in vivo.

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    Dingkun Gui

    Full Text Available Glucose-induced reactive oxygen species (ROS production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN. Here, we tested the hypothesis that Astragaloside IV(AS-IV exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg(-1·d(-1 for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation.

  1. Mammographically detected breast arterial calcifications: Indicators for arteriosclerotic diseases?

    Energy Technology Data Exchange (ETDEWEB)

    Taskin, Fuesun [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey)]. E-mail: fusuntaskin@yahoo.com; Akdilli, Alev [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Karaman, Can [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Unsal, Alparslan [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Koeseoglu, Kutsi [Adnan Menderes University, Faculty of Medicine, Department of Radiology, 09100 Aydin (Turkey); Ergin, Filiz [Adnan Menderes University, Faculty of Medicine, Department of Public Health, Aydin (Turkey)

    2006-11-15

    Purpose: To determine the prevalence of breast arterial calcifications (BAC) detected on mammography and search for conditions that may influence their existence. Materials and methods: The mammograms of 6156 consecutive patients were reevaluated for the presence of BAC. Four hundred eighty-five women having BAC were enrolled in the patient group. Additionally, randomly selected 500 women, without BAC constituted the control group. Hospital records of the participants were reviewed for parity, menopausal status, oral contraceptive agent (OCA) usage, hormone replacement therapy (HRT) usage, presence of diabetes, hypertension, hyperlipidemia, albuminuria and history of myocardial infarction (MI). Results: Prevalence of BAC was 7.9% on mammograms. Ninety-four women were aged between 40 and 49 years, 165 were aged between 50 and 59 years and 226 were over 60 years among BAC positive 485 women. A significant relationship was found for the frequency of BAC versus age and HRT usage in all age groups (p < 0.05). Similarly, significant relationships were also found for the frequency of BAC versus OCA usage, HRT usage, hyperlipidemia and diabetes in age group of 40-49 and in age group of 50-59, and for the frequency of BAC versus albuminuria in age group of 40-49, BAC versus history of myocardial infarction in age group of 59-59 and over 60 years (p < 0.05). The correlations were not significant for the relationships of BAC with OCA usage, hyperlipidemia, diabetes and albuminuria in women over 60 years (p > 0.05). Conclusion: Most benign findings like BAC are not routinely reported during mammographic evaluation. Our study showed that, presence of BAC on mammography was strongly related to advancing age. However, these findings may signify a systemic risk and can be used as precautious indicators for undocumented systemic diseases, especially in premenopausal women.

  2. CRP polymorphisms and chronic kidney disease in the third national health and nutrition examination survey

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    Glenn Kimberly

    2011-05-01

    Full Text Available Abstract Background CRP gene polymorphisms are associated with serum C-reactive protein concentrations and may play a role in chronic kidney disease (CKD progression. We recently reported an association between the gene variant rs2808630 and CKD progression in African Americans with hypertensive kidney disease. This association has not been studied in other ethnic groups. Methods We used data from 5955 participants from Phase 2 of The Third National Health and Nutrition Examination Survey (1991-1994 to study the association between CRP polymorphisms and CKD prevalence in a population-based sample. The primary outcome was CKD defined as estimated glomerular filtration rate (eGFR CRP gene, rs2808630, rs1205, rs3093066, rs1417938, rs3093058, and rs1800947, were evaluated. Results CRP rs2808630 AG compared to the referent AA genotype was associated with CKD in non-Hispanic blacks (n = 1649, 293 of whom had CKD with an adjusted odds ratio (OR of 3.09 (95% CI 1.65-5.8; p = 0.001. For the secondary outcomes, rs2808630 AG compared to the referent AA genotype was associated with albuminuria with an adjusted OR of 3.07 (95% CI 1.59-5.94; p = 0.002, however not with eGFR. There was no association between the SNPs and CKD, albuminuria or eGFR in non-Hispanic whites or Mexicans Americans. Conclusions In this cross-sectional study, the 3' flanking CRP gene variant rs2808630 was associated with CKD, mainly through its association with albuminuria in the non-Hispanic blacks. Despite not finding an association with eGFR, our results support our previous study demonstrating an association between CRP gene variant rs2808630 and CKD progression in a longitudinal cohort of African American with hypertensive kidney disease.

  3. An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney.

    Science.gov (United States)

    Arias, Simone Costa Alarcon; Souza, Renata Alves; Malheiros, Denise Maria Avancini Costa; Fanelli, Camilla; Fujihara, Clarice Kazue; Zatz, Roberto

    2016-01-15

    We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.

  4. High prevalence and associated risk factors for impaired renal function and urinary abnormalities in a rural adult population from southern China.

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    Qinghua Liu

    Full Text Available BACKGROUND: The prevalence of chronic kidney disease (CKD has increased and will continue to rise worldwide. However, data regarding the prevalence of CKD in a rural area of China are limited. We therefore investigated the prevalence and associated risk factors of impaired renal function and urinary abnormalities in an adult rural population in southern China. METHODS: Between December 2006 and January 2007, residents older than 20 years from four villages in Zhuhai city were randomly selected using a stratified, multistage sampling technique. All participants were interviewed and tested for hematuria, albuminuria and estimated glomerular filtration rate (eGFR. The associations between age, gender, diabetes mellitus, hypertension, hyperuricemia, education level and indicators of renal damage were examined. RESULTS: Overall, 1,214 subjects were enrolled in this study. After adjustment for age and gender, the prevalence of albuminuria was 7.1% (95% CI: 4.5, 8.1, reduced eGFR was 2.6% (95% CI: 1.7%, 3.3%, and hematuria was 4.6% (95% CI: 3.3%, 6.0%. Approximately 13.6% (95% CI: 12.0%, 15.1% of the patients had at least one indicator of renal damage, but only 8.3% were previously aware. Age, diabetes, hyperlipidemia, hypertension, hyperuricemia, use of nephrotoxic medications, coronary heart disease and history of CKD were independently associated with impaired renal function and urinary abnormalities. Additionally, age, diabetes, and hypertension were independently associated with albuminuria. Age, hypertension, hyperuricemia, central obesity, and coronary heart disease were independently associated with reduced renal function. CONCLUSIONS: The high prevalence and low awareness of impaired renal function and urinary abnormalities in this population illustrates the urgent need to implement a CKD prevention program in the rural areas of southern China.

  5. Renal Evaluation in Women with Preeclampsia

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    T.A. Facca

    2012-05-01

    Full Text Available Background/Aims: Preeclampsia (PE is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group by performing urinary tests. Results: Mean (±SD age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001. Mean (±SD urinary RBP (p = 0.017, albuminuria (p = 0.002, and urinary albumin concentration (UAC ratio (p = 0.006 of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002, and 3,778.9 ± 4,296.6 mg/g (p = 0.006, respectively. Mean (±SD urine PCR in the PE group was 6.7 ± 6.1 g/g (p Conclusions: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.

  6. Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management.

    Science.gov (United States)

    Akbari, Ayub; Clase, Catherine M; Acott, Phil; Battistella, Marisa; Bello, Aminu; Feltmate, Patrick; Grill, Allan; Karsanji, Meena; Komenda, Paul; Madore, Francois; Manns, Braden J; Mahdavi, Sara; Mustafa, Reem A; Smyth, Andrew; Welcher, E Sohani

    2015-02-01

    We congratulate the KDIGO (Kidney Disease: Improving Global Outcomes) work group on their comprehensive work in a broad subject area and agreed with many of the recommendations in their clinical practice guideline on the evaluation and management of chronic kidney disease. We concur with the KDIGO definitions and classification of kidney disease and welcome the addition of albuminuria categories at all levels of glomerular filtration rate (GFR), the terminology of G categories rather than stages to describe level of GFR, the division of former stage 3 into new G categories 3a and 3b, and the addition of the underlying diagnosis. We agree with the use of the heat map to illustrate the relative contributions of low GFR and albuminuria to cardiovascular and renal risk, though we thought that the highest risk category was too broad, including as it does people at disparate levels of risk. We add an albuminuria category A4 for nephrotic-range proteinuria and D and T categories for patients on dialysis or with a functioning renal transplant. We recommend target blood pressure of 140/90mm Hg regardless of diabetes or proteinuria, and against the combination of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors. We recommend against routine protein restriction. We concur on individualization of hemoglobin A1c targets. We do not agree with routine restriction of sodium intake to 3.3g/d). We suggest screening for anemia only when GFR is 60mg/mmol or proteinuria with protein excretion > 1g/d as the referral threshold for proteinuria.

  7. Inhibition of Sodium-GlucoseCotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease

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    Daniel Rodriguez

    2015-12-01

    Full Text Available Background/Aims: Dapagliflozin (DAPA is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2 which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD has not been studied. Methods: We examined the effect of DAPA in the Han: SPRD rat model of PKD. DAPA (10 mg/kg/day or vehicle (VEH was administered orally via gavage to 5 week old male Han: SPRD (Cy/+ or control (+/+ rats (n = 8-9 per group for 5 weeks. Blood and urine were collected at baseline and after 2.5 and 5 weeks of treatment to assess renal function and albuminuria. At the end of the treatment, rats were sacrificed and kidneys were excised for histological analysis. Results: After 5 weeks of treatment, DAPA-treated Cy/+ and +/+ rats exhibited significantly higher glucosuria, water intake and urine output than VEH-treated rats. DAPA-treated Cy/+ rats also exhibited significantly higher clearances for creatinine and BUN and less albuminuria than VEH-treated Cy/+ rats. DAPA treatment for 5 weeks resulted in a significant increase of the kidney weight in Cy/+ rats but no change in cyst growth. The degree of tubular epithelial cell proliferation, macrophage infiltration and interstitial fibrosis was also similar in DAPA-and VEH-treated Cy/+ rats. Conclusion: The induction of glucosuria with the SGLT2-specific inhibitor DAPA was associated with improved renal function and decreased albuminuria, but had no effect on cyst growth in Cy/+ rats. Overall the beneficial effects of DAPA in this PKD model were weaker than the previously described effects of the combined SGLT1/2 inhibitor phlorizin.

  8. A meta-analysis of bevacizumab combined with chemotherapy in the treatment of ovarian cancer

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    T S Wang

    2014-01-01

    Full Text Available Introduction: Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta-analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. Materials and Methods: We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression-free survival (PFS, overall survival (OS, and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF, neutrophils, thrombosis, and bleeding. The Hazard ratio (HR and relative risk were used for the meta-analysis and were expressed with 95% confidence intervals (CIs. All the statistical analyses were carried out by  Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA. Results: We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46-0.82; P 0.05; the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall 0.05. Conclusion: Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils

  9. The association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    李冬梅

    2013-01-01

    Objective To evaluate the association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients.Methods A total of 594 patients with type2 diabetes were enrolled from the inpatients of the Nanjing Medical University Affiliated Nanjing Hospital.Fasting serum lipid profile,25-hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated.The relationship between nephropathy and vitamin D deficiency (<20μg/L) or insufficiency (20-<30μg/L) was analyzed.Results Nephropathy was found in 177subjects (29.8%) with albuminuria in 141 and proteinu-

  10. Childhood sarcoidosis in Denmark 1979-1994: incidence, clinical features and laboratory results at presentation in 48 children

    DEFF Research Database (Denmark)

    Hoffmann, A L; Milman, N; Byg, K E

    2004-01-01

    .7-15). In 1979-1994 the incidence was 0.29 per 100000 person-years children children aged 14-15 y. General malaise, fever, weight loss, abdominal discomfort, respiratory symptoms, lymphadenopathy...... examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. CONCLUSION: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features...... that are different from the appearance of those in older children and often constitute a diagnostic challenge. In older children, the clinical appearance has many features in common with the presentation in adults....

  11. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

    DEFF Research Database (Denmark)

    Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin;

    2009-01-01

    , caregivers, and researchers were blinded to treatment assignment. During a median follow-up of 4.7 years, 793 patients discontinued therapy and 63 were lost to follow-up. MEASUREMENTS: Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 microg/min or greater, then 2...... further collections were done. The primary end point was new microalbuminuria (3 or 4 collections of urinary albumin excretion rate >or=20 microg/min). The secondary end point was rate of change in albuminuria. RESULTS: Individual and pooled results of the 3 trials showed that candesartan had little...

  12. Preeclampsia prediction in type 1 diabetes and diurnal blood pressure methodology

    DEFF Research Database (Denmark)

    Lauszus, Finn

    2016-01-01

    of ambulatory blood pressure measurements in pregnancy and in particular in women with type 1 diabetes. Diabetic pregnancy is complicated with a 50% risk of hypertension/preeclampsia. In the nonpregnant, diabetic women minute increases in blood pressure as well as in albuminuria are forerunners for incipient....... Preeclampsia is associated with urinary albumin excretion rate, reduced night/day ratio, and elevated diurnal blood pressure from first trimester and onwards. However, due to blunting of the diurnal variation, the night/day rhythm provides no good prediction of preeclampsia. Diurnal measurement is a valuable...

  13. Incidence of diabetic macular edema and associated risk factors in a cohort of patients with type 1 diabetes in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Malin Lundberg

    and at follow-up in 2011. At baseline, median age and duration of diabetes was 21.8 and 12.3 years, respectively. Two field fundus photos were taken, retinopathy was graded in accordance to ETDRS and macular microaneurysms (MA) were counted. Baseline measurements included HbA1c, albuminuria, blood pressure...... and BMI. At follow-up SD-OCT were performed. Incident DME was defined as former central laser treatment or current DME on OCT. Excluded were patients with DME at baseline (n=1) and patients without fundus photos and OCT at follow-up (n=2). Incidence of DME was calculated and logistic regression was made...

  14. Associations between plasma tenofovir concentration and renal function markers in HIV-infected women

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    Mwila Mulubwa

    2016-02-01

    Full Text Available Background: Tenofovir disoproxil fumarate (TDF has been associated with kidney tubulardys function and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV concentration with renal function; no such studies to date have been performed on Africans.Objective: To investigate the correlation between plasma tenofovir (TFV concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART.These markers were also compared to a HIV-uninfected control group.Methods: HIV-infected women (n = 30 on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR, creatinine clearance (CrCl, serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t-tests were applied in the statistical analyses.Results: TFV concentration was independently associated with albuminuria (adjusted r2 = 0.339; p = 0.001 in HIV-infected women. In the adjusted (weight analysis, eGFR (p = 0.038,CrCl (p = 0.032 and albuminuria (p = 0.048 were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR (p < 0.001 and CrCl (p = 0.008 increased from baseline to follow-up in HIV-infected women.Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

  15. Nontraditional Cardiovascular Biomarkers and Estimation of Cardiovascular Risk in Predialysis Chronic Kidney Disease Patients and Their Correlations With Carotid Intima Media Thickness

    OpenAIRE

    Sathi, Satyanand; Mahapatra, Himanshu; Sunder, Sham; Jayaraman, Rajesh; Sharma, Neera; Verma, Himanshu; Krishnamoorthy, Venkataramanan; Gupta, Anurag; Kanchi, Prabhu; Daksh, Sunil; Pursnani, Lalit; Shadab, Faisal; Singh, Manveer

    2014-01-01

    Background: Cardiovascular biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), hs-CRP (high sensitivity C-reactive protein), and albuminuria predict underlying heart disease in the general population as well as CKD patients. Objectives: We aimed to study the association of NT-proBNP, cTnT, hs-CRP, and spot urine albumin creatinine ratio with carotid intima media thickness (CIMT) for cardiovascular risk estimation in predialysis CKD (chronic kid...

  16. Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

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    Grigory Sidorenkov

    Full Text Available BACKGROUND: Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. METHODS: A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR with 95% confidence intervals. RESULTS: Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94. Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93. Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89. CONCLUSION: Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient

  17. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper;

    2016-01-01

    angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels. The placebo period was considered reference and all......Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin...

  18. Urinary microRNA-29 correlates with urinary albumin in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    钟美容

    2014-01-01

    Objective To investigate the possibility of urinary microRNA-29(miR-29)as biomarker for diabetic nephropathy in patients with type 2 diabetes.Methods Sixty-one patients with type 2 diabetes were divided into 2groups:diabetes with normoalbuminuria[n=25,(58.88±11.75)years old]and diabetes with albuminuria[n=36,(62.19±13.11)years old].There were no significant differences in age and gender between groups.The

  19. Insulin directly stimulates VEGF-A production in the glomerular podocyte

    OpenAIRE

    Hale, L. J.; Hurcombe, J.; Lay, A.; Santamaría, B.; Valverde, A M; Saleem, M A; Mathieson, P. W.; Welsh, G. I.; Coward, R. J.

    2013-01-01

    Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the po...

  20. PP005. Vitamin D depletion aggravates hypertension in transgenic rats

    DEFF Research Database (Denmark)

    Bjørkholt Andersen, Louise; Herse, Florian; Christesen, Henrik Thybo;

    2013-01-01

    overexpressing the human renin and angiotensinogen genes, group 1 (n=18) received vitamin D depleted chow; group 2 (n=15) standard chow and intraperitoneal paricalcitol at 800ng/kg thrice weekly; and group 3 (n=15) standard chow and vehicle injections. Blood pressure (tail cuff) and 24-h albuminuria were...... found between groups in mortality or proteinuria. CONCLUSION: Short-term vitamin D depletion aggravated hypertension and end-organ damage in a rat model of angiotensin II-induced hypertension. Short-term interventions with high-dose vitamin D analogues had no protective effect....

  1. Obesity - a risk factor of renal pathology in patients with type 2 diabetes mellitus

    OpenAIRE

    Svetlana Alekseevna Savel'eva; Aleksandra Aleksandrovna Kryachkova; Kseniya Olegovna Kurumova; Minara Shamkhalovna Shamkhalova; Irina Mikhaylovna Kutyrina; Marina Vladimirovna Shestakova

    2010-01-01

    Aim. To study association between obesity and renal pathology in patients with type 2 diabetes mellitus (DM2). Materials and methods. The study included 106 patients with CD2 (41 men and 65 women) of mean age 60.0+-7.0 years. Exclusion criteria were duration of DM2 less than 5 years and manifest diabetic nephropathy (DN) (glomerular filtraton rate (GFR) below 60 ml/min/m2, albuminuria over 2 g/24 hr). Anthropometric parameters measured included body mass index (BMI). Serum creatinine...

  2. Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

    DEFF Research Database (Denmark)

    Jensen, T; Richter, Erik; Feldt-Rasmussen, Bo;

    1988-01-01

    To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal...... were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy...

  3. Measurement of the modification and interference rate of urinary albumin detected by size-exclusion HPLC

    International Nuclear Information System (INIS)

    The measurement of the excretion of urinary albumin (albuminuria) is an important and well-established method to assess clinical outcomes. A high-performance liquid chromatography (HPLC) method has been introduced to measure albuminuria. Using this method, it was found that commonly used immunological methods do not measure a fraction of urinary albumin. Some authors presumed that the reason of immuno-unreactivity is the modification of urinary albumin; some others presumed that the difference is merely because of interference. In order to decide this question, we established an HPLC method equipped with tandem UV and fluorescent detection to assess the changes in the detectability of albumin with the rate of modification. For this measurement, differently modified forms of albumin were used. Urine samples of diabetic patients were also measured to find a potential connection between the modification rate and clinical parameters. Secondly, we have established a reversed phase HPLC method to assess the interference rate. We conclude that albumin modification does not affect immunoreactivity. The modification rate of urinary albumin in diabetic patients showed a correlation with renal function. The interference rate of the albumin peak was found to be 12.7% on average, which does not explain the difference between the two methods

  4. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

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    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  5. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

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    Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China); Yang, Z. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Department of Pathology, Xi' an, China, Department of Pathology, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Yuan, Z.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China)

    2014-03-03

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13{sup BN} rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

  6. Influence of chronic kidney disease on cardiac structure and function.

    Science.gov (United States)

    Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef

    2015-09-01

    Chronic kidney disease (CKD), the presence of kidney dysfunction and/or damage, is a worldwide public health issue. Although CKD is independently associated with various subtypes of cardiovascular diseases, a recent international collaborative meta-analysis demonstrates that CKD is particularly strongly associated with heart failure, suggesting its critical impact on cardiac structure and function. Although numerous studies have investigated the association of CKD and cardiac structure and function, these studies substantially vary regarding source populations and methodology (e.g., measures of CKD and/or parameters of cardiac structure and function), making it difficult to reach universal conclusions. Nevertheless, in this review, we comprehensively examine relevant studies, discuss potential mechanisms linking CKD to alteration of cardiac structure and function, and demonstrate clinical implications as well as potential future research directions. We exclusively focus on studies investigating both CKD measures, kidney function (i.e., glomerular filtration rate [GFR], creatinine clearance, or levels of filtration markers), and kidney damage represented by albuminuria, since current international clinical guidelines of CKD recommend staging CKD and assessing its clinical risk based on both GFR and albuminuria. PMID:26194332

  7. Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats

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    Ramdas Pandhare

    2012-09-01

    Full Text Available Objective: The aim of the present study was to investigate the renal protective effect of Adenanthera pavonina (A. pavonina seed aqueous extract (APSAE, in streptozotocin (STZ-induced diabetic rats.Materials and Methods: The renal protective effect of A. pavonina seed aqueous extract (APSAE was studied in STZ-induced diabetic rats. APSAE (50, 100 and 200 mg/kg per day was given daily to diabetic rats for 13 weeks. Blood glucose, serum parameters such as albumin, creatinine, total protein, urea, lipid profile, glycated haemoglobin (HbA1c, and urine parameters such as urine protein and albumin were examined. Kidney histopathology was also done. Results: After 13 weeks of treatment, in STZ-induced diabetic rats, severe hyperglycemia was developed, with marked increase in proteinuria and albuminuria. However, APSAE treatment significantly reduced proteinuria, albuminuria, lipid levels, and HbA1c deposition in diabetic rats. Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

  8. Circulating CXCL16 in Diabetic Kidney Disease

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    Usama Elewa

    2016-09-01

    Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

  9. Association between microalbuminuria and subclinical atherosclerosis evaluated by carotid artery intima-media in elderly patients with normal renal function

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    Kong XiangLei

    2012-06-01

    Full Text Available Abstract Background Moderate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT and microalbuminuria in elderly patients with normal renal function. Methods Subjects were 272 elderly patients (age  ≥ 60 years with normoalbuminuria (n = 238 and microalbuminuria (n = 34. Carotid IMT was measured by means of high-resolution B-mode ultrasonography. Estimated glomerular filtration rate (eGFR ≥ 60 ml/min/1.73 m2 was defined as normal renal function. Those who had macroalbuminuria and atherosclerotic vascular disease were not included. Results Compared to subjects with normoalbuminuria, subjects with microalbuminuria had higher mean carotid IMT (1.02 ± 0.38 vs. 0.85 ± 0.28 mm; P  Conclusions A slight elevation of albuminuria is a significant determinant of carotid IMT independent of traditional cardiovascular risk factors in our patients. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis when microalbuminuria is found in elderly patients, although with normal renal function.

  10. ED 04-3 ASSESSMENT OF RENAL FUNCTION DURING FOLLOW UP OF HYPERTENSIVE SUBJECTS.

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    Ito, Sadayoshi

    2016-09-01

    The presence of chronic kidney disease (CKD) is a strong risk factor not only for end stage kidney disease (ESKD) but also cerebro-cardiovascular disease (CVD). CKD is defined as GFR < 60ml/min/1.73m and/or the evidence of renal damages for more than 3 months. Epidemiological studies have shown that albuminuria even as little as 10mg/gCr is a strong risk factor for CVD, especially stroke. The significance of albuminuria can be recognized when we think of the fact that the amount of albumin in 24 hour-GFR is as large as 6 kg (4.0g/dL × 150 L/day) in normal: why such a miniscule amount of albumin in urine (as little as 10 mg of 6 kg) can be so closely related to CVD even in the presence of normal GFR? We have pointed out that in vital organs such as brain, heart and kidney, there are unique circulatory system where microvessels are branched off directly from large high pressure arteries. We refer these vessel as Strain Vessel, and have shown that close linkage between microalbuminuria CVD is based on strain vessel injuries. In addition, we have recently shown that urine pH is associated with vascular and renal damages. In this lecture, I will discuss the meaning of measurement of urinary protein (albumin) and pH as well as renal function during follow up of hypertensive subjects. PMID:27643069

  11. Conformational Transitions and Glycation of Serum Albumin in Patients with Minimal-Change Glomerulopathy

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    Hong, Sae Yong; Lee, Eun Young; Yang, Jong Oh; Kim, Tae Yeong; Kim, Eun Hee; Cheong, Mi Young; Kim, Soo Hyun; Cheong, Chae Joon

    2004-01-01

    Background There has been a lack of study on the structural changes of serum albumin in patients with minimal change disease (MCD). To determine whether glycation and/or conformational transitions of albumin are involved in the pathogenesis of albuminuria, nine patients with MCD were enrolled in a prospective follow-up study for comparison of these parameters in serum albumin during the remission and relapse of nephrotic syndrome. Methods Circular dichroism measurements were made with purified albumin. Ellipticities at each wavelength were transformed to mean residue ellipticity. Monosaccharide composition was analyzed by high-pH anion-exchange chromatography with pulsed amperometric detection. Results There was no difference in the proportions of α-helix, β-conformation, and β-turn of albumin between the sera of control patients and those with nephrotic syndrome. However, the proportion of the random configuration was slightly higher in the plasma albumin of patients in relapse than in those in remission. The proportion of the random configuration was lower in the albumin of the serum than in the urine of patients with nephrotic syndrome, but there was no difference in the proportions of α-helix, β-conformation, and β-turn of albumin between their plasma and urine. Conclusion Our results suggest that conformational changes in albumin are involved in albuminuria in patients with MCD. PMID:15481604

  12. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

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    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  13. THE COMPARATIVE COST-EFFICACY ANALYSIS OF VARIOUS ANTIHYPERTENSIVE THERAPIES

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    S. V. Malchikova

    2016-01-01

    Full Text Available Aim. To perform the comparative cost-efficacy analysis of various antihypertensive therapies in hypertensives patients.Material and methods. 140 hypertensive patients with history of ineffective antihypertensive therapy were randomized in to 4 groups, 35 patients in each one. Patients of Group A received indapamide retard plus perindopril; group B - indapamide retard plus amlodipine; group C - amlodipine plus lisinopril; group D - amlodipine plus bisoprolol. The Russian version of general questionnaire MOS-SF-36 was applied for quality of a life estimated. Endothelium function was evaluated with B-mode ultrasonography (Acuson 128 ХР/10. Albuminuria level was detected by immunoturbometric method (Integra-700, Roche.Results. The drug combination B had the least cost. The drug combination C was the most effective. The drug combination C was the most economically rational. The drug combination A was the least economically rational for BP reduction. However the drug combination A was comparable with drug combination C in effects on quality of life and on endothelium function, and it was the most economically rational for albuminuria reduction.Conclusion. Indapamide retard plus perindopril combination is the most economically rational in patients with target-organ lesions (nephropathy. Lisinopril plus amlodipine combination is economically rational in patients without target-organ lesions. 

  14. THE COMPARATIVE COST-EFFICACY ANALYSIS OF VARIOUS ANTIHYPERTENSIVE THERAPIES

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    S. V. Malchikova

    2009-01-01

    Full Text Available Aim. To perform the comparative cost-efficacy analysis of various antihypertensive therapies in hypertensives patients.Material and methods. 140 hypertensive patients with history of ineffective antihypertensive therapy were randomized in to 4 groups, 35 patients in each one. Patients of Group A received indapamide retard plus perindopril; group B - indapamide retard plus amlodipine; group C - amlodipine plus lisinopril; group D - amlodipine plus bisoprolol. The Russian version of general questionnaire MOS-SF-36 was applied for quality of a life estimated. Endothelium function was evaluated with B-mode ultrasonography (Acuson 128 ХР/10. Albuminuria level was detected by immunoturbometric method (Integra-700, Roche.Results. The drug combination B had the least cost. The drug combination C was the most effective. The drug combination C was the most economically rational. The drug combination A was the least economically rational for BP reduction. However the drug combination A was comparable with drug combination C in effects on quality of life and on endothelium function, and it was the most economically rational for albuminuria reduction.Conclusion. Indapamide retard plus perindopril combination is the most economically rational in patients with target-organ lesions (nephropathy. Lisinopril plus amlodipine combination is economically rational in patients without target-organ lesions. 

  15. KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Management of Blood Pressure in CKD

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    Taler, Sandra J.; Agarwal, Rajiv; Bakris, George L.; Flynn, Joseph T.; Nilsson, Peter M.; Rahman, Mahboob; Sanders, Paul W.; Textor, Stephen C.; Weir, Matthew R.; Townsend, Raymond R.

    2014-01-01

    In response to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for blood pressure management in patients with chronic kidney disease not on dialysis, the National Kidney Foundation organized a group of US experts in hypertension and transplant nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The overriding message was the dearth of clinical trial evidence to provide strong evidence-based recommendations. For patients with CKD with normal to mildly increased albuminuria, goal blood pressure has been relaxed to ≤140/90 mm Hg for both diabetic and nondiabetic patients. In contrast, KDIGO continues to recommend goal blood pressure ≤130/80 mm Hg for patients with chronic kidney disease with moderately or severely increased albuminuria and for all renal transplant recipients regardless of the presence of proteinuria, without supporting data. The expert panel thought the KDIGO recommendations were generally reasonable but lacking in sufficient evidence support and that additional studies are greatly needed. PMID:23684145

  16. ASK1 Inhibitor Halts Progression of Diabetic Nephropathy in Nos3-Deficient Mice.

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    Tesch, Greg H; Ma, Frank Y; Han, Yingjie; Liles, John T; Breckenridge, David G; Nikolic-Paterson, David J

    2015-11-01

    p38 mitogen-activated protein kinase (MAPK) signaling promotes diabetic kidney injury. Apoptosis signal-regulating kinase (ASK)1 is one of the upstream kinases in the p38 MAPK-signaling pathway, which is activated by inflammation and oxidative stress, suggesting a possible role for ASK1 in diabetic nephropathy. In this study, we examined whether a selective ASK1 inhibitor can prevent the induction and progression of diabetic nephropathy in mice. Diabetes was induced in hypertensive endothelial nitric oxide synthase (Nos3)-deficient mice by five low-dose streptozotocin (STZ) injections. Groups of diabetic Nos3(-/-) mice received ASK1 inhibitor (GS-444217 delivered in chow) as an early intervention (2-8 weeks after STZ) or late intervention (weeks 8-15 after STZ). Control diabetic and nondiabetic Nos3(-/-) mice received normal chow. Treatment with GS-444217 abrogated p38 MAPK activation in diabetic kidneys but had no effect upon hypertension in Nos3(-/-) mice. Early intervention with GS-444217 significantly inhibited diabetic glomerulosclerosis and reduced renal dysfunction but had no effect on the development of albuminuria. Late intervention with GS-444217 improved renal function and halted the progression of glomerulosclerosis, renal inflammation, and tubular injury despite having no effect on established albuminuria. In conclusion, this study identifies ASK1 as a new therapeutic target in diabetic nephropathy to reduce renal inflammation and fibrosis independent of blood pressure control. PMID:26180085

  17. Serum Cystatin C, Markers of Chronic Kidney Disease, and Retinopathy in Persons with Diabetes

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    Chee Wai Wong

    2015-01-01

    Full Text Available Purpose. We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR. Methods. We examined 1,119 Indian adults with diabetes, aged 40–80 years, who participated in the Singapore Indian Eye Study (2007–2009, a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c. Results. The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1% compared to CKD defined separately by creatinine (26.6%, cystatin C (20.9%, and albuminuria (23.4%. People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI = 13.63 (6.08–30.54 compared to those without CKD by any marker. Nearly half (48.7% of participants with cystatin C ≥ 1.12 mg/L have moderate DR. Conclusions. CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes.

  18. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy.

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    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  19. Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia.

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    Naohiko Imai

    Full Text Available Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients.A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated.Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001 and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001 were significant predictors of urinary L-FABP levels.Urinary L-FABP is strongly associated with anemia in non-diabetic patients.

  20. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Science.gov (United States)

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  1. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

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    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  2. A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome

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    The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis

  3. Predictors of angiotensin-converting enzyme inhibitor-induced reduction of urinary albumin excretion in nondiabetic patients.

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    van de Wal, Ruud M A; Gansevoort, Ron T; van der Harst, Pim; Boomsma, Frans; Thijs Plokker, H W; van Veldhuisen, Dirk J; de Jong, Paul E; van Gilst, Wiek H; Voors, Adriaan A

    2006-11-01

    Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity. We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects, without renal disease. In addition, we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric patients were included. Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded, randomized treatment (fosinopril 20 mg or placebo). Mean age was 51.1+/-11.5 years, and 65.6% were male. Median urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial pressure (beta(standardized)=0.161; P=0.006), urinary sodium excretion (beta(standardized)=0.154; P=0.011), and estimated renal function were independently associated with albumin excretion. In these predominantly normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by 18.5% versus a 6.1% increase on placebo after 3 months (Poutspoken in subjects with higher baseline albumin excretion. Based on our data, we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure-lowering agents in subjects with higher baseline levels of albuminuria. PMID:17000930

  4. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    International Nuclear Information System (INIS)

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure

  5. Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus

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    Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Reis, Janice Sepúlveda; Campos, Fernanda Magalhães Freire; Dusse, Luci Maria S.; Carvalho, Maria das Graças; Braga Gomes, Karina; Fernandes, Ana Paula

    2016-01-01

    This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m2), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m2), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy. PMID:26770985

  6. Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Caroline Pereira Domingueti

    2016-01-01

    Full Text Available This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m2, n=65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m2, n=60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P=0.001, P<0.001, P<0.001, P<0.001, and P<0.001, resp.. Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist. INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy.

  7. Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

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    Junghyun Kim

    2012-01-01

    Full Text Available Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS, which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c, and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.

  8. Thiamine deficiency and its correlation with dyslipidaemia in diabetics with microalbuminuria

    International Nuclear Information System (INIS)

    Objective: To measure and correlate the levels of thiamine and dyslipidaemia in microalbuminuric diabetics. Methods: Cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, from January 2009 to December 2010, and comprised 60 known diabetic patients, who were inducted from diabetic clinics of Rawalpindi. These patients were divided into three equal groups, with group I (n=20) being normal healthy individuals, group II comprised of microalbuminurics type 2 diabetics (n=20) and group III (n=20) were macroalbuminuric type 2 diabetics, based on their albumin excretion rate. The healthy volunteers (n=20) had blood glucose less than 6 mmol/L and were inducted as the comparison group. Fasting blood samples of diabetic and control groups were analysed for glucose, glycosylated haemoglobin, lipid profile, thiamine chloride and thiamine monophosphate. Besides, 24-hour urine samples were analysed for microalbuminuria, thiamine chloride and thiamine monophosphate. Results: Plasma thiamine chloride and thiamine monophosphate levels were found to be significantly (p<0.001) reduced in the diabetics (n=60) compared to the controls (n=20). Furthermore, there was a progressive decline in these levels with increasing albuminuria; the lowest being in the macroalbuminuric group (group IV). Urinary thiamine levels were significantly (p<0.001) higher in the diabetics compared to the controls. These changes were more pronounced as albuminuria level increased; the highest being in group IV. The parameters of lipid profile, including triglycerides, total cholesterol and low-density lipoprotein cholesterol, were significantly (p<0.001) higher in diabetics and showed progressive increase with worsening albuminuria. Whereas, the high-density lipoprotein cholesterol levels were significantly (p<0.001) reduced in diabetics and showed progressive decline as the microalbuminuria status worsened. Furthermore, a

  9. Metabolic Syndrome without Diabetes or Hypertension Still Necessitates Early Screening for Chronic Kidney Disease: Information from a Chinese National Cross-Sectional Study.

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    Daqing Hong

    Full Text Available Metabolic syndrome (MS is prevalent, with an increasing contribution to the incidence of chronic kidney disease (CKD. The study of the relationship between them is important. The CKD survey, a national cross-sectional study, provided a large database to accomplish this study. The study population were 41 131 adults from this survey between 2008 and 2009. CKD was defined as estimate glomerular filtration rate (eGFR less than 60 mL/min per 1.73 m2 or the presence of albuminuria. MS was diagnosed by National Cholesterol Education Program-Adult Treatment Panel III (ATPIII, ATPIII-modified or International Diabetes Federation (IDF criteria. Logistic regression model was applied to study the impact of MS or its components on CKD or its components. The age and sex standardized prevalence of MS by ATPIII, ATPIII-modified and IDF criteria was 11.77% (11.13%-12.40%, 21.51% (20.69%-22.34% and 16.67% (15.92-17.42% respectively. Multivariate logistic regression models showed that MS and its components were associated with higher CKD prevalence. The risk for CKD and its components increased with the number of MS components. After adjusting for hypertension and diabetes, the odds ratios of MS for CKD decreased, but remained significantly more than 1 between 1.16(95%CI 1.07-1.26 and 1.37 (95% CI 1.25-1.50 across the different models. Similar results were found with albuminuria, while for decreased eGFR, after adjusting for hypertension and diabetes, the odds ratios of MS and MS components (except elevated TG became insignificant. In conclusion, MS is prevalent and associated with a higher prevalence of CKD. Different MS components are associated with different risks for CKD, even after adjusting for hypertension and diabetes, which may mainly be contributed more by the increased risk for albuminuria than that for decreased eGFR. More attention must be paid to the population with MS, including those with elevated blood pressure and serum glucose.

  10. Prevalence and Risk Factors of CKD in Chinese Patients with Periodontal Disease

    Science.gov (United States)

    Chen, Wei; Liang, Mengjun; Luo, Wei; Wu, Xianfeng; Ruan, Yiping; Wang, Jie; Xu, Ricong; Zhan, Xiaojiang; Yu, Jianwen; Tan, Jiaqing; Dong, Xiuqing; Zhang, Jincai; Yu, Xueqing

    2013-01-01

    Background Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD). We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China. Methods In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed. Results A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7–3.7), 6.7% (95% CI 5.5–8.1) and 10.9% (95% CI 9.2–12.5), respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2–20.3). Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L) were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP) (≥1.03 mg/L) and TNF-α levels (≥1.12 ng/L) were independently associated with an increased risk of albuminuria. Female, lower education (

  11. Prevalence and risk factors of CKD in Chinese patients with periodontal disease.

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    Kejin Liu

    Full Text Available BACKGROUND: Periodontal disease is common among adults and is associated with an increasing risk of chronic kidney disease (CKD. We aimed to investigate the prevalence and risk factors of CKD in patients with periodontal disease in China. METHODS: In the current cross-sectional study, patients with periodontal disease were included from Guangdong Provincial Stomatological Hospital between March 2011 and August 2011. CKD was defined as estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m(2, the presence of albuminuria, or hematuria. All patients with periodontal disease underwent a periodontal examination, including periodontal probing pocket depth, gingival recession, and clinical attachment level by Florida Probe. They completed a questionnaire and had blood and urine samples taken. The adjusted prevalence of indicators of kidney damage was calculated and risk factors associated with CKD were analyzed. RESULTS: A total of 1392 patients with periodontal disease were invited to participate this study and 1268 completed the survey and examination. After adjusting for age and sex, the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7-3.7, 6.7% (95% CI 5.5-8.1 and 10.9% (95% CI 9.2-12.5, respectively. The adjusted prevalence of CKD was 18.2% (95% CI 16.2-20.3. Age, male, diabetes, hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (≥7.54 ng/L were independent risk factors for reduced eGFR. Female, diabetes, hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high sensitivity C-reactive protein (hsCRP (≥ 1.03 mg/L and TNF-α levels (≥ 1.12 ng/L were independently associated with an increased risk of albuminuria. Female, lower education (

  12. Five-year incidence of chronic kidney disease (stage 3-5 and associated risk factors in a Spanish cohort: the MADIABETES Study.

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    Miguel A Salinero-Fort

    Full Text Available To evaluate the incidence rate of Chronic Kidney Disease (CKD stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m2 among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners in Madrid (Spain.The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12-11.44 and the incidence density was 2.07 (95% CI = 1.83-2.33 cases per 1,000 patient-months or 2.48 (95% CI = 2.19-2.79 cases per 100 patient-years. The highest hazard ratio (HR for developing CKD stage 3-5 was albuminuria ≥ 300 mg/g (HR = 4.57; 95% CI= 2.46-8.48. Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13-4.81, a history of Hypertension (HR = 2.02; 95% CI = 1.42-2.89, Myocardial Infarction (HR= 1.72; 95% IC= 1.25-2.37, Dyslipidemia (HR = 1.68; 95% CI 1.30-2.17, duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88 and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02-2.24.After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5. Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.

  13. Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

    Science.gov (United States)

    Salinero-Fort, Miguel A.; San Andrés-Rebollo, Francisco J.; de Burgos-Lunar, Carmen; Gómez-Campelo, Paloma; Chico-Moraleja, Rosa M.; López de Andrés, Ana; Jiménez-García, Rodrigo

    2015-01-01

    Objective To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m2) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use. Design The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). Results The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24). Conclusions After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM. PMID:25856231

  14. Angiopoietins and diabetic nephropathy.

    Science.gov (United States)

    Gnudi, Luigi

    2016-08-01

    Diabetic nephropathy is the main cause of end-stage renal failure in the Western world. In diabetes, metabolic and haemodynamic perturbations disrupt the integrity of the glomerular filtration barrier, leading to ultrastructural alterations of the glomeruli, including podocyte foot process fusion and detachment, glomerular basement membrane thickening, reduced endothelial cell glycocalyx, and mesangial extracellular matrix accumulation and glomerulosclerosis, ultimately leading to albuminuria and end-stage renal disease. Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology. In normal physiology angiopoietins regulate the function of the glomerular filtration barrier. When they are dysregulated, however, as they are in diabetes, they drive the cellular mechanisms that mediate diabetic glomerular pathology. Modulation of angiopoietins expression and signalling has been proposed as a tool to correct the cellular mechanisms involved in the pathophysiology of diabetic microvascular disease, such as retinopathy in humans. Future work might evaluate whether this novel therapeutic approach should be extended to diabetic kidney disease. PMID:27207083

  15. Metabolic Syndrome, Chronic Kidney, and Cardiovascular Diseases: Role of Adipokines

    Directory of Open Access Journals (Sweden)

    Manfredi Tesauro

    2011-01-01

    Full Text Available Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD. Albuminuria is a major risk factor for cardiovascular diseases (CVDs. Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.

  16. Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus

    DEFF Research Database (Denmark)

    Vistisen, Dorte; Andersen, Gregers Stig; Hansen, Christian Stevns;

    2016-01-01

    AND RESULTS: From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including......BACKGROUND: Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. METHODS...... range, 2.9-10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent...

  17. Rationale and design of ARTS

    DEFF Research Database (Denmark)

    Pitt, Bertram; Filippatos, Gerasimos; Gheorghiade, Mihai;

    2012-01-01

    AIMS: BAY 94-8862 is a novel, non-steroidal, mineralocorticoid receptor antagonist with greater selectivity than spironolactone and stronger mineralocorticoid receptor binding affinity than eplerenone. The aims of the MinerAlocorticoid Receptor Antagonist Tolerability Study (ARTS; NCT01345656......) are to evaluate the safety and tolerability of BAY 94-8862 in patients with heart failure associated with a reduced left ventricular ejection fraction (HFREF) and chronic kidney disease (CKD), and to examine the effects on biomarkers of cardiac and renal function. Methods ARTS is a multicentre, randomized, double....... placebo (primary endpoint) and vs. spironolactone, safety and tolerability, biomarkers of cardiac and renal function or injury, eGFR, and albuminuria. BAY 94-8862 pharmacokinetics are also assessed. Perspectives ARTS is the first phase II clinical trial of BAY 94-8862 and is expected to provide a wealth...

  18. Plasmin in urine from patients with type 2 diabetes and treatment-resistant hypertension activates ENaC in vitro

    DEFF Research Database (Denmark)

    Buhl, Kristian B; Stolzenburg Oxlund, Christina; Friis, Ulla G;

    2014-01-01

    diabetes mellitus (T2DM) and treatment-resistant hypertension excrete plasmin(ogen) in urine in proportion to albumin and that plasmin confers to urine the ability to activate ENaC. METHOD:: Patients (n = 113) with T2DM and resistant hypertension, defined as systolic blood pressure (SBP) more than 130 mm...... of plasmin in preurine may inappropriately activate ENaC in patients with type 2 diabetes and microalbuminuria. This may contribute to treatment-resistant hypertension.......BACKGROUND:: Aberrant filtration of plasminogen from plasma and subsequent activation to plasmin in the urinary space may activate proteolytically the epithelial sodium channel, ENaC. In conditions with chronic albuminuria, this may cause hypertension. It was hypothesized that patients with type 2...

  19. Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment

    DEFF Research Database (Denmark)

    von Scholten, B J; Lajer, M; Goetze, J P;

    2015-01-01

    AIMS: Glucagon-like peptide-1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure (SBP). The aim was to investigate the time course of the anti-hypertensive effect of liraglutide treatment and potential underlying mechanisms. METHODS: We used an open...... weeks of maximum dose. Reductions in ECV and MR-proANP may explain the anti-hypertensive potential. Liraglutide treatment was associated with reversible reductions in albuminuria and GFR, which has to be confirmed in randomized trials.......-label, single-centre trial; 31 participants with Type 2 diabetes and hypertension completed the study. All participants were treated with liraglutide escalated to a maximum dose of 1.8 mg/day for 7 weeks, followed by a 21-day washout period. The primary outcome was a change in 24-h SBP. RESULTS: Twenty...

  20. Determinants of Intravascular Resistance in Indian Diabetic Nephropathy Patients: A Hospital-Based Study

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    Anubhav Thukral

    2011-01-01

    Full Text Available Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.

  1. Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies

    DEFF Research Database (Denmark)

    Christensen, P K; Hommel, E E; Clausen, P;

    1999-01-01

    BACKGROUND: The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients...... with nondiabetic nephropathies is not known. METHODS: We investigated the effect of acute lowering of blood pressure (BP) on GFR in 16 (8 males and 8 females) albuminuric subjects suffering from different nondiabetic nephropathies and in 14 (7 males and 7 females) controls matched with respect to sex, age, BP......, and baseline GFR. The subjects received in random order an intravenous injection of either clonidine (150 to 225 microg) or saline (0.154 mmol/liter) within two weeks. We measured GFR ([51Cr]-EDTA), albuminuria (enzyme-linked immunosorbent assay; ELISA), and BP (Takeda TM-2420). RESULTS: Clonidine induced...

  2. Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, J; Smidt, U M

    1985-01-01

    The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance...... induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0.......01), and plasma volume raised slightly from 2916 to 2995 ml (p less than 0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent...

  3. The need for combination antihypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials?

    Science.gov (United States)

    Struijker-Boudier, H A J; Ambrosioni, E; Holzgreve, H; Laurent, S; Mancia, G; Ruilope, L M; Waeber, B

    2007-09-01

    Pharmacological treatment of hypertension represents a cost-effective way for preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment blood pressure (BP) should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has recently been shown in controlled interventional trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving macrovascular stiffness. Fixed-dose combinations are becoming more and more popular and are even proposed by current hypertension guidelines as a first-line option to treat hypertensive patients. PMID:17686100

  4. SPECTRUM OF ACUTE GLOMERULO NEPHRITIS IN CHILDREN AT GOVERNMENT GENERAL HOSPITAL, ANANTAPURAMU

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2015-04-01

    Full Text Available AIM: Aim of the study is to study the spectrum of AGN in children and to assess the age, sex and seasonal incidence and prognostic factors. Acute glomerulonephritis is one of the most common condition seen in children. The study group included 50 children. In most of the children presenting complaints s of are puffiness of face, haematuria and oliguria. METHODS AND MATERIALS: Fifty children who were admitted in the government hospital during the period of September 2013 to January 2015 were included in the stud y. RESULTS: The maximum admissions were seen from the months of September to December. Common age group was between 3 and 8 years. Rare age group was below 2 years. Hypertension was noticed in 32 out of 50 children. Albuminuria and hematuria were commonest urinary abnormalities. CONCLUSION: acute glomerulonephritis is less common below 2 years. Hypertension was of varying degree. Cardiomegaly by x - ray was an added feature.

  5. A comparative study of microvascular complications in patients with secondary and type 1 diabetes

    DEFF Research Database (Denmark)

    Larsen, S; Hilsted, J; Philipsen, E K;

    1990-01-01

    The prevalence of retinopathy, albuminuria, and neuropathy were assessed in 25 patients with insulin-requiring diabetes secondary to chronic pancreatitis and in 25 patients with Type 1 (insulin-dependent) diabetes, matched for age at diabetes onset (secondary, 39 +/- 11 (+/- SD) years vs Type 1, 38...... +/- 11 years) and duration of diabetes (10 +/- 6 vs 10 +/- 7 years). The prevalence of retinopathy was significantly higher in Type 1 diabetic patients (52%) than those with secondary diabetes (20%) (p less than 0.02). Median urinary excretion of albumin was 9 (range 1-206) mg 24-h-1 in patients...... with Type 1 diabetes and 7 (1-90) mg 24-h-1 in patients with secondary diabetes (NS). One secondary diabetic patient and five Type 1 diabetic patients had microalbuminuria (NS). Vibration perception threshold (measured at the big toe) was identical in the two groups of patients, and no patient had...

  6. Targeting the aldosterone pathway in cardiovascular disease

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Azizi, Michel; Bauersachs, Johann;

    2012-01-01

    Accumulated evidence has demonstrated that aldosterone is a key player in the pathogenesis of cardiovascular (CV) disease. Multiple clinical trials have documented that intervention in the aldosterone pathway can reduce blood pressure and lower albuminuria and improve outcome in patients with heart...... failure or myocardial infarction. Recent studies have unraveled details about the role of aldosterone at the cellular level in CV disease. The relative importance of glucocorticoids and aldosterone in terms of mineralocorticoid receptor activation is currently being debated. Also, studies are addressing...... which aldosterone modulator to use, which timing of treatment to aim for, and in which population to intervene. This review provides an overview of recent developments in the understanding of the role of aldosterone in CV disease, with particular reference to mechanisms and potential targets...

  7. Evidence of changes in renal charge selectivity in patients with type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Kverneland, A; Feldt-Rasmussen, B; Vidal, P;

    1986-01-01

    Altered filtration of macromolecules due to decreased electrical charge of the glomerular basement membrane might be the initial step in the development of albuminuria in patients with Type 1 (insulin-dependent) diabetes mellitus. We therefore investigated the selectivity index, i.e. renal...... clearance of non-glycated plasma albumin/clearance of glycated plasma albumin in 38 patients with Type 1 diabetes mellitus. The two albumin molecules differed slightly in charge, non-enzymatic glycated albumin being more anionic at physiological pH compared with unmodified plasma albumin. Glycated albumin...... in plasma and urine was determined by a specific, sensitive and highly reproducible chromatographic procedure. In diabetic patients with normal urinary albumin excretion, the selectivity index was increased three-fold compared with that of non-diabetic subjects (2 p less than 0.01). A significant...

  8. Piperidine renin inhibitors: from leads to drug candidates.

    Science.gov (United States)

    Märki, H P; Binggeli, A; Bittner, B; Bohner-Lang, V; Breu, V; Bur, D; Coassolo, P H; Clozel, J P; D'Arcy, A; Doebeli, H; Fischli, W; Funk, C H; Foricher, J; Giller, T; Grüninger, F; Guenzi, A; Güller, R; Hartung, T; Hirth, G; Jenny, C H; Kansy, M; Klinkhammer, U; Lave, T; Lohri, B; Luft, F C; Mervaala, E M; Müller, D N; Müller, M; Montavon, F; Oefner, C H; Qiu, C; Reichel, A; Sanwald-Ducray, P; Scalone, M; Schleimer, M; Schmid, R; Stadler, H; Treiber, A; Valdenaire, O; Vieira, E; Waldmeier, P; Wiegand-Chou, R; Wilhelm, M; Wostl, W; Zell, M; Zell, R

    2001-01-01

    Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status. PMID:11347960

  9. Pulmonary renal syndrome: treatment of acute renal failure secondary to double positive goodpasture syndrome

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    Rajkumar Prakashbhai Doshi

    2016-01-01

    Full Text Available This is a case of a 34 year old female who presented with lower epigastric pain, flank pain and hematuria. Her symptoms started two days after being treated on Trimethoprim+Sulfamethoxazole for urinary tract infection. Worsening of her symptoms despite switching to Cephalexin prompted her to come to the emergency department. On admission, her creatinine was 5.3 mg/dL with potassium of 5.2 mEq/L and albuminuria of 100 mg/dL. Chest computed tomography (CT without contrast revealed findings consistent with goodpasture disease. Biopsy of the kidney confirmed diffuse necrotizing and crescentic glomerulonephritis consistent with anti-glomerular basement membrane antibody disease. She was treated with plasmapheresis and steroids with complete resolution of symptoms at follow up. [Int J Res Med Sci 2016; 4(1.000: 322-325

  10. Diabetes and Kidney Disease: Role of Oxidative Stress

    Science.gov (United States)

    Jha, Jay C.; Banal, Claudine; Chow, Bryna S.M.; Cooper, Mark E.

    2016-01-01

    Abstract Significance: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657–684. PMID:26906673

  11. Establish Albumin-creatinine Ratio Reference Value of Adults in the Rural Area of Hebei Province

    Institute of Scientific and Technical Information of China (English)

    Qiao-jing Liang; Wen Huang; Guo-juan Zhang; Ning-li Wang

    2016-01-01

    Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province. Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dyslipidemia, cardiovascular and cerebrovascular diseases, kidney diseases, and overweight condition, as well as those with an estimated glomerular filtration rate (eGFR) Results The normal upper limit of ACR was 28.71 mg/g (3.25 mg/mmol) for males and 31.85 mg/g (3.60 mg/mmol) for females. Based on this ACR reference value, the age-gender standardized prevalence of albuminuria in the rural areas of Hebei province was 12.9%. Conclusion The ACR reference value in the rural of Hebei province is higher than that of the Western population.

  12. Tenofovir induced Fanconi syndrome: A possible pharmacokinetic interaction

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    Jigar Kapadia

    2013-01-01

    Full Text Available Tenofovir was introduced as a second line drug for the treatment of human immunodeficiency virus (HIV infection in India in December 2009. Although rare, renal toxicity is a recognized adverse drug reaction (ADR of this drug, especially when administered with boosted lopinavir-ritonavir. In this case, an HIV positive patient receiving tenofovir based antiretroviral therapy (ART for last 1 year developed albuminuria, glycosuria and hypophosphatemia. Renal function tests and random blood sugar were within normal limits. He was diagnosed as a case of tenofovir induced Fanconi syndrome. Tenofovir was discontinued and patient was prescribed an alternate regimen. Five months later clinical symptoms and renal functions returned to normal. A pharmacokinetic interaction between tenofovir and ritonavir may have resulted in the toxicity. A periodic monitoring of renal functions is desirable in patients on tenofovir based ART.

  13. GENETICS ASPECTS OF DIABETIC NEPHROPATHY

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    Oana-Elena Sauca

    2010-09-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alteration, and various growth and genetic factors. The identification of the main genes would allow the detection of those individuals at high risk for diabetic nephropathy and better understanding of its pathophysiologyas well.The present review discusses the main information available in literature regarding some genetic variants (involved in the renin-angiotensin system, glucose and lipid metabolism and some cytoskeleton proteins that reaffirms the importance of genetic factors in diabetic nephropathy.

  14. Asymptomatic coronary artery disease in Type-2 diabetes

    International Nuclear Information System (INIS)

    Objective: To select a subgroup of type-2 diabetics with two additional pre specified risk factors to see that whether there is any benefit of screening such patients. Methodology: Five hundred twenty six patients were sent for treadmill stress test or thallium scan. Those who had abnormal results were advised coronary angiography. The angiographically proven CAD was correlated with various risk factors to find the relationship between the disease and variables. Results: Two hundred thirty five (48%) patients had abnormal results and among them 158 (67%)underwent coronary angiography. Among these 21% had evidence of CAD. Coronary artery bypass grafting (CABG) was performed in 35(33%) patients, catheter based intervention (PCI) in 44(40%) patients and 30(27%) patients were not suitable for intervention. Duration of diabetes, smoking, diabetic retinopathy, albuminuria, and peripheral vascular disease were significant predictor of asymptomatic CAD. Conclusion: This study has demonstrated strong relationship between risk factors and asymptomatic CAD in type 2 diabetics. (author)

  15. The Prevalence of 25-hydroxyvitamin D Deficiency in Japanese Patients with Diabetic Nephropathy.

    Science.gov (United States)

    Kondo, Masumi; Toyoda, Masao; Miyatake, Han; Tanaka, Eitaro; Koizumi, Masahiro; Komaba, Hirotaka; Kimura, Moritsugu; Umezono, Tomoya; Fukagawa, Masafumi

    2016-01-01

    Objective The purpose of this study was to measure serum 25-hydroxyvitamin D [25(OH)D] levels in Japanese patients with diabetic nephropathy and determine the relationship between 25(OH)D concentrations and various factors. Methods The study subjects included 442 patients with type 2 diabetes. Their serum levels of creatinine, HbA1c, intact-parathyroid hormone, urinary albumin, 25(OH)D, and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured and their estimated glomerular filtration rate (eGFR) was determined. The patients were divided into four groups based on the risk for progression to chronic kidney disease (CKD): low, moderate, high, very high, based on their eGFR and their level of albuminuria. Results The median 25(OH)D level was 14.6 ng/mL; 11% of the patients had 25(OH)D deficiency (<10 ng/mL), and 2% of patients had active vitamin D deficiency, as defined by a 1,25(OH)2D level of <22 pg/mL. The serum 25(OH)D level was correlated with the serum 1,25(OH)2D level in patients with a very high risk for CKD, but not in those with a moderate or high risk for CKD. Conclusion Although the vitamin D levels of the Japanese patients with diabetic nephropathy and CKD were low, the prevalence of vitamin D deficiency, as defined by the 1,25(OH)2D level, was low. Albuminuria, younger age, and female gender were associated with a low 25(OH)D level. The serum level of 25(OH)D should be monitored to assess the vitamin D status of patients with nephropathy and CKD. PMID:27629947

  16. Promoting effects of the adipokine, apelin, on diabetic nephropathy.

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    Bao-hai Zhang

    Full Text Available Angiogenesis, increased glomerular permeability, and albuminuria are thought to contribute to the progression of diabetic nephropathy (DN. Apelin receptor (APLNR and the endogenous ligand of APLNR, apelin, induce the sprouting of endothelial cells in an autocrine or paracrine manner, which may be one of the mechanisms of DN. The aim of this study was to investigate the role of apelin in the pathogenesis of DN. Therefore, we observed apelin/APLNR expression in kidneys from patients with type 2 diabetes as well as the correlation between albuminuria and serum apelin in patients with type 2 diabetes. We also measured the proliferating, migrating, and chemotactic effects of apelin on glomerular endothelial cells. To measure the permeability of apelin in glomerular endothelial cells, we used transwells to detect FITC-BSA penetration through monolayered glomerular endothelial cells. The results showed that serum apelin was significantly higher in the patients with type 2 diabetes compared to healthy people (p<0.05, Fig. 1B and that urinary albumin was positively correlated with serum apelin (R = 0.78, p<0.05. Apelin enhanced the migration, proliferation, and chemotaxis of glomerular endothelial cells in a dose-dependent manner (p<0.05. Apelin also promoted the permeability of glomerular endothelial cells (p<0.05 and upregulated the expression of VEGFR2 and Tie2 in glomerular endothelial cells (p<0.05. These results indicated that upregulated apelin in type 2 diabetes, which may be attributed to increased fat mass, promotes angiogenesis in glomeruli to form abnormal vessels and that enhanced apelin increases permeability via upregulating the expression of VEGFR2 and Tie2 in glomerular endothelial cells.

  17. 探讨低蛋白饮食对2型糖尿病早期肾病的影响%The effect of low-protein diet on type -2 diabetic early nephropathy

    Institute of Scientific and Technical Information of China (English)

    李纲

    2010-01-01

    目的 探讨低蛋白饮食对2型糖尿病早期肾病在肾功能和营养状况方面的影响.方法 住院及门诊134例早期肾病患者,按就诊顺序分为低蛋白治疗组和正常蛋白组,实验期为1年.结果 两组患者体重指数、血常规及血液生化、血糖指标、肾功能等方面治疗后差异无统计学意义.治疗后两组间血清白蛋白比较差异有统计学意义.实验组尿白蛋白排泄率明显下降.结论 低蛋白膳食可以显著减少2型糖尿病早期肾病患者尿蛋白排泄率,从而改善营养状况,保护肾功能.%Objective To discuss the effect of a low-protein diet or type 2 diabitic nephropathy in renal function and nutritional aspect. Methods One hundred and thirty-four patients treated in hospital or by clinic doctors with microalbuminuria was conducted into two groups with 67 assigned to a protein-restricted diet and 67 assingned to normal protein diet in one year. Results In test group albuminuria decreased significantly (P<0.01).The patients blood glucose, total choiesterol,triglyceride,body mass inder (BMI) had not significant difference between two groups. Conclusions Protein-restricted diet beneficially reduced albuminuria in type 2 diabetes mellitus with microalbuminuria, so as to improve nutritional status and delay the development and progression of diabetic nephropathy.

  18. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

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    Frank Y Ma

    Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  19. Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality

    Science.gov (United States)

    Zabeen, Bedowra; Craig, Maria E.; Virk, Sohaib A.; Pryke, Alison; Chan, Albert K. F.; Cho, Yoon Hi; Benitez-Aguirre, Paul Z.; Hing, Stephen; Donaghue, Kim C.

    2016-01-01

    Objective To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Research Design and Methods Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. Results Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes. Conclusions In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES. PMID:27050468

  20. Manifestation of renal disease in obesity: pathophysiology of obesity-related dysfunction of the kidney

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    John A D’Elia

    2009-11-01

    Full Text Available John A D’Elia, Bijan Roshan, Manish Maski, Larry A WeinrauchJoslin Diabetes Center, Renal Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston and Cambridge, MassachusettsAbstract: Albuminuria in individuals whose body mass index exceeds 40 kg/m2 is associated with the presence of large glomeruli, thickened basement membrane and epithelial cellular (podocyte distortion. Obstructive sleep apnea magnifies glomerular injury as well, probably through a vasoconstrictive mechanism. Insulin resistance from excess fatty acids is exacerbated by decreased secretion of high molecular weight adiponectin from adipose cells in the obese state. Adiponectin potentiates insulin in its post-receptor signaling resulting in glucose oxidation in mitochondria. Recent studies of podocyte physiology have concentrated on the structural and functional requirements that prevent glomerular albumin leakage. The architecture of the podocyte involves nephrin and podocin, proteins that cooperate to keep slit pores between foot processes competent to retain albumin. Insulin and adiponectin are necessary for high-energy phosphate generation. When fatty acids bind to albumin, the toxicity to proximal renal tubules is magnified. Albumin and fatty acids are elevated in urine of individuals with obesity related nephrotic syndrome. Fatty acid accumulation and resistin inhibit insulin and adiponectin. Study of cytokines produced by adipose tissue (adiponectin and leptin and macrophages (resistin has led to a better understanding of the relationship between weight and hypertension. Leptin, is presumably secreted after food intake to inhibit the midbrain/ hypothalamic appetite centers. Resistance to leptin results in excess signaling to hypothalamic sympathetics leading to hypertension. Demonstration of the existence of a cerebral receptor mutation provide evidence for a role in hypertension of a central nervous

  1. Effects of Tumor Necrosis Factor-α on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy

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    Choon Hee Chung

    2015-02-01

    Full Text Available Background/Aims: Tumor necrosis factor (TNF-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1 by enzyme-linked immunosorbent assay (ELISA. TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-κB, phosphatidylinositol 3-kinase (PI3K or Akt. In vivo studies were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-α and MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and correlated with albuminuria. Results: Podocytes treated with TNF-α showed a robust increase (∼900% in the secretion of MCP-1, induced in a dose- and time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, which was inducible by TNF-α ligand, but did not depend on TNFR1. TNF-α then proceeded via the NF-κB and the PI3K/Akt systems, based on the effectiveness of the inhibitors of those pathways. For in vivo relevance to diabetic kidney disease, TNF-α and MCP-1 levels were found to be elevated in the urine of db/db mice but not in the plasma. Conclusion: TNF-α potently stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF-κB and PI3K/Akt pathways. Both TNF-α and MCP-1 levels were increased in the urine of diabetic db/db mice, correlating with the severity of diabetic albuminuria.

  2. Hyperhomocysteinaemia, vascular related pregnancy complications and the response to vitamin supplementation in pregnant women of Pakistan

    International Nuclear Information System (INIS)

    To elaborate the relationship between serum homocysteine (hcy) levels and vascular related pregnancy complications in pregnant women as well as to assess the homocysteine lowering effects of folate, vitamin B12 and B6. The secondary objectives were to establish a link between serum homocysteine levels and maternal age, parity, gestational age, foetal birth weight, mean arterial pressure and albuminuria. Methods: A total of 332 pregnant women (gestational age: >24 weeks) attending Liaquat University Hospital Hyderabad, Pakistan, were enrolled. Of these 112 were healthy normal pregnant women; 61 pregnant women had pre-eclampsia, 49 with eclampsia and 110 with placental abruption. A cohort of 30 patients with elevated hcy levels (>8.2 mu mol/liter), were given folate, vitamin B12 and B6 as supplements for 6 weeks. Fasting blood samples were collected, centrifuged and stored at 2 to 8 deg. C. Hcy levels were determined by IMx immunoassay. Results: Higher serum hcy levels, higher mean arterial blood pressure (MAP), pre-term deliveries and low foetal birth weights were noted in women with pregnancies complicated by pre-eclampsia and eclampsia as compared to control and those with placental abruption. Significant hcy lowering effects of folate, vitamin B12 and B6 supplementation were observed. Significant and positive correlation was found between hhcy and MAP (r = 0.001; p<0.001), albuminuria (r = 0.004; p< 0.01) and low birth weights (r= 0.05; p<0.06). Conclusion: Higher hcy levels in pregnancies complicated by pre-eclampsia and eclampsia have been noted. Data support the hypothesis that folate, vitamin B12 and B6 lower hcy levels in hyperhomocysteinaemic women. (author)

  3. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population-based cohort.

    Science.gov (United States)

    Calhoun, David A; Booth, John N; Oparil, Suzanne; Irvin, Marguerite R; Shimbo, Daichi; Lackland, Daniel T; Howard, George; Safford, Monika M; Muntner, Paul

    2014-03-01

    Refractory hypertension is an extreme phenotype of antihypertensive treatment failure. Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a large (n=30 239), population-based cohort were evaluated to determine the prevalence of refractory hypertension and associated cardiovascular risk factors and comorbidities. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on ≥5 antihypertensive drug classes. Participants with resistant hypertension (systolic/diastolic, ≥140/90 mm Hg on ≥3 or hypertension served as comparator groups. Of 14 809 REGARDS participants receiving antihypertensive treatment, 78 (0.5%) had refractory hypertension. The prevalence of refractory hypertension was 3.6% among participants with resistant hypertension (n=2144) and 41.7% among participants on ≥5 antihypertensive drug classes. Among all participants with hypertension, black race, male sex, living in the stroke belt or buckle, higher body mass index, lower heart rate, reduced estimated glomerular filtration rate, albuminuria, diabetes mellitus, and history of stroke and coronary heart disease were associated with refractory hypertension. Compared with resistant hypertension, prevalence ratios for refractory hypertension were increased for blacks (3.00; 95% confidence interval, 1.68-5.37) and those with albuminuria (2.22; 95% confidence interval, 1.40-3.52) and diabetes mellitus (2.09; 95% confidence interval, 1.32-3.31). The median 10-year Framingham risk for coronary heart disease and stroke was higher among participants with refractory hypertension when compared with those with either comparator group. These data indicate that although resistant hypertension is relatively common among treated patients with hypertension, true antihypertensive treatment failure is rare.

  4. 妊娠高血压综合征视网膜病变相关危险因素分析%Analysis of related risk factors of retinopathy in pregnancy induced hypertension syndrome

    Institute of Scientific and Technical Information of China (English)

    高新宇

    2015-01-01

    目的:分析妊娠高血压综合征( pregnancy induced hypertension syndrome ,PIHS)视网膜病变相关危险因素。  方法:选取PIHS视网膜病变患者262例,观察PIHS分期、年龄、体质量、蛋白尿、平均动脉压、红细胞比容与PIHS视网膜病变的相关性。  结果:视网膜分期随着 PIHS 级别的增高而增高(χ2回归=52.13, P0.05);体质量越大,视网膜病变程度越高(χ2回归=22.97, P  结论:PIHS分期、体质量、蛋白尿、平均动脉压、红细胞比容均是PIHS视网膜病变的相关危险因素。%•AlM:To analyze the related risk factors of retinopathy in pregnancy induced hypertension syndrome ( PlHS) . •METHODS:Two hundred and sixty-two cases with the PlHS retinal lesions were selected, and the correlation between PlHS stage, age, body mass, albuminuria, mean arterial blood pressure, hematocrit value and retinopathy in PlHS were observed. •RESULTS: Retinal stage increased with the increase of the grade of PlHS (χ2regression=52. 13, P0. 05);the greater body mass was, the higher the degree of retinopathy was (χ2regression=22. 97, P •CONCLUSlON: PlHS stage, body mass, albuminuria, mean arterial blood pressure, hematocrit value are the related risk factors of retinopathy in PlHS.

  5. C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid-derived suppressor cells to blame?

    Science.gov (United States)

    Pegues, Melissa A; McWilliams, Ian L; Szalai, Alexander J

    2016-07-01

    Myeloid-derived suppressor cells (MDSCs) are a CD11b(+)Gr1(+) population in mice that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent suppressors of T cell immunity, and their contribution has been investigated in a plethora of diseases including renal cancer, renal transplant, and chronic kidney disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury (AKI) remains unknown. Herein, using human C-reactive protein (CRP) transgenic (CRPtg) and CRP-deficient mice (CRP(-/-)) subjected to bilateral renal ischemia-reperfusion injury (IRI), we confirm our earlier finding that CRP exacerbates renal IRI and show for the first time that this effect is accompanied in CRPtg mice by a shift in the balance of kidney-infiltrating MDSCs toward a suppressive Ly6G(+)Ly6C(low) g-MDSC subtype. In CRPtg mice, direct depletion of g-MDSCs (using an anti-Gr1 monoclonal antibody) reduced the albuminuria caused by renal IRI, confirming they play a deleterious role. Remarkably, treatment of CRPtg mice with an antisense oligonucleotide that specifically blocks the human CRP acute-phase response also led to a reduction in renal g-MDSC numbers and improved albuminuria after renal IRI. Our study in CRPtg mice provides new evidence that MDSCs participate in the pathogenesis of renal IRI and shows that their pharmacological depletion is beneficial. If ongoing investigations confirm that CRP is an endogenous regulator of MDSCs in CRPtg mice, and if this action is recapitulated in humans, then targeting CRP or/and MDSCs might offer a new approach for the treatment of AKI. PMID:27053688

  6. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

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    Lucia Pacifico

    2016-07-01

    Full Text Available The association between nonalcoholic fatty liver disease (NAFLD and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001. The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001. Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57; p < 0.05 independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.

  7. Targeting T helper 17 by mycophenolate mofetil attenuates diabetic nephropathy progression.

    Science.gov (United States)

    Kim, Su-Mi; Lee, Sang-Ho; Lee, Arah; Kim, Dong-Jin; Kim, Yang-Gyun; Kim, Se-Yun; Jeong, Kyung-Hwan; Lee, Tae-Won; Ihm, Chun-Gyoo; Lim, Sung-Jig; Moon, Ju-Young

    2015-10-01

    Proinflammatory T helper 1 (Th1) and T helper 17 (Th17) cell subsets have been reported to have an immunopathogenic role in metabolic disease. We previously demonstrated that CD4(+) T cells are increased in kidneys in type 2 diabetic patients. However, the role of Th1 and Th17 cells in the development and progression of diabetic nephropathy is unclear. In this study, we examined the hypothesis that mycophenolate mofetil (MMF) attenuates diabetic kidney injury by the suppression of renal T-cell proliferation and related cytokines. Four groups of male C57/BL6 mice (8-weeks-old) were studied: (1) untreated controls, (2) MMF-treated controls (30 mg/kg of body weight per day), (3) streptozotocin (STZ)-induced diabetes, and (4) MMF-treated STZ-induced diabetes. The interferon gamma (IFN-γ) and interleukin 17 (IL-17) from renal CD4(+) T cells were analyzed in kidney mononuclear cells by flow cytometry. We found proliferating CD4(+) T cells were significantly increased in the kidney compared with the spleen. There were increases in IFN-γ(+) CD4(+) and IL-17A(+) CD4(+) T cells from the initiation of albuminuria in the kidneys of diabetic mice. We found MMF suppresses only the intrarenal IL-17A(+) CD4(+) T cells from early diabetic nephropathy and improves albuminuria, tubulointerstitial fibrosis independent of glycemic control. Our study results suggest that Th17 may play an independent role in the progression of diabetic nephropathy and modulation of IL-17 has potential as an immunologic therapeutic target. PMID:26001596

  8. Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications.

    Science.gov (United States)

    Kumar Vr, Santhosh; Darisipudi, Murthy N; Steiger, Stefanie; Devarapu, Satish Kumar; Tato, Maia; Kukarni, Onkar P; Mulay, Shrikant R; Thomasova, Dana; Popper, Bastian; Demleitner, Jana; Zuchtriegel, Gabriele; Reichel, Christoph; Cohen, Clemens D; Lindenmeyer, Maja T; Liapis, Helen; Moll, Solange; Reid, Emma; Stitt, Alan W; Schott, Brigitte; Gruner, Sabine; Haap, Wolfgang; Ebeling, Martin; Hartmann, Guido; Anders, Hans-Joachim

    2016-06-01

    Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

  9. Nephroprotective effect of heparanase in experimental nephrotic syndrome.

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    Suheir Assady

    Full Text Available Heparanase, an endoglycosidase that cleaves heparan sulfate (HS, is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS in a mouse model.BALB/c wild-type (wt mice and heparanase overexpressing transgenic mice (hpa-TG were tail-vein injected with either Adriamycin (ADR, 10 mg/kg or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.Our results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

  10. Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study

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    Liu, Kathleen D.; Yang, Wei; Go, Alan S.; Anderson, Amanda H.; Feldman, Harold I.; Fischer, Michael J.; He, Jiang; Kallem, Radhakrishna R.; Kusek, John W.; Master, Stephen R.; Miller, Edgar R.; Rosas, Sylvia E.; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R.; Hsu, Chi-yuan

    2015-01-01

    Background Chronic kidney disease is common and associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration—based markers (such as serum creatinine or albuminuria). Study Design Cohort study, Chronic Renal Insufficiency Cohort (CRIC) Study. Setting & Participants 3386 participants with estimated glomerular filtration rate of 20-70 mL/min/1.73 m2 enrolled from June 2003 through August 2008. Predictor Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Outcomes Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke or peripheral artery disease) and death through March 2011. Measurements Urine NGAL concentration measured at baseline with a two-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). Results There were 428 heart failure events (during 16383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16584 person-years of follow-up) and 522 deaths (during 18214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors and cardiac medications, higher urine NGAL levels remained independently associated with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/ml] vs. lowest [≤6.9 ng/ml] quintile, 1.83 [95% CI, 1.20-2.81]; HR, per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Limitations Urine NGAL was measured only once. Conclusions Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were independently associated with future ischemic atherosclerotic

  11. Association between urinary albumin excretion and intraocular pressure in type 2 diabetic patients without renal impairment.

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    Jin A Choi

    Full Text Available BACKGROUND: To assess the relationship between urinary albumin excretion and intraocular pressure (IOP in type 2 diabetes patients without renal impairment. METHODS: We explored the effects of albuminuria on high IOP in 402 non-glaucomatous type 2 diabetes without renal impairment who participated in the 2011 Korean National Health and Nutrition Examination Survey (KNHANES. Multiple logistic regression analysis was used to assess the relationship between log-transformed albumin/creatinine ratio (ACR tertiles and an IOP of ≥ 18 mmHg after adjusting for age, gender, hypertension, body mass index, triglycerides, area of residence, and education level. RESULTS: Subjects with a high IOP ≥ 18 mmHg were more likely to be current smokers (P = 0.038, heavy drinkers (P = 0.006, and to have high systolic blood pressure (P = 0.016, triglycerides (P = 0.008, and a higher log-transformed ACR (P = 0.022.In multivariate regression analysis, ACR tertile was associated with the prevalence of high IOP significantly (P = 0.022. The associations between ACR tertiles and high IOP were significant in overweight patients and those with abdominal obesity (P = 0.003 and 0.003, respectively. In contrast, there were no associations in the subgroup of patients who were not overweight and those without abdominal obesity (P = 0.291 and 0.561, respectively. CONCLUSIONS: Urinary albumin excretion is associated with high IOP in the type 2 diabetes population without renal insufficiency. The effect of the albuminuria on IOP was evident in a subgroup of patients with components of metabolic syndrome.

  12. Different regulation of miR-29a-3p in glomeruli and tubules in an experimental model of angiotensin II-dependent hypertension: potential role in renal fibrosis.

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    Castoldi, Giovanna; di Gioia, Cira; Giollo, Fabrizio; Carletti, Raffaella; Bombardi, Camila; Antoniotti, Marco; Roma, Francesca; Zerbini, Gianpaolo; Stella, Andrea

    2016-03-01

    The aim of this study was to evaluate the role of the angiotensin II (Ang II) induced-differential miRNA expression in renal glomerular and tubulo-interstitial fibrosis in an experimental model of Ang II-dependent hypertension. To clarify this issue, Sprague Dawley rats were treated with Ang II (200 ng/kg per minute, n = 15) or physiological saline (n = 14) for 4 weeks. Systolic blood pressure and albuminuria were measured every 2 weeks. At the end of the experimental period, renal glomerular and tubulo-interstitial fibrosis was evaluated by histomorphometric analysis, after Sirius-Red and Masson's trichrome staining. Ang II increased systolic blood pressure (P < 0.0001), albuminuria (P < 0.01) and both glomerular and tubulo-interstitial fibrosis (P < 0.01). Using laser capture microdissection and miRNA microarray analysis this study showed that miR-29a-3p was down-regulated in renal tubules and up-regulated in glomeruli. Real-time polymerase chain reaction (PCR) experiments confirmed in Ang II-treated rats a down-regulation of miR-29a-3p in tubules (P < 0.01), while no significant changes were observed in glomeruli. Matrix metalloproteinase-2 (MMP-2) was identified as putative miR-29a-3p target (by TargetScan, miRanda, Tarbase software) and functionally confirmed by luciferase activity assay. These data demonstrate that the effects of Ang II on miR-29a-3p expression in renal tubules is different from the one exerted in the glomeruli and that miR-29a-3p targets MMP-2. These results suggest that the development of renal fibrosis at glomerular and tubulo-interstitial level depends on different molecular mechanisms. PMID:26700017

  13. Association between diabetes complications and leukocyte counts in Iranian patients

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    Moradi S

    2012-01-01

    Full Text Available Sedigheh Moradi1, Scott Reza Jafarian Kerman2, Farzaneh Rohani1, Fereshteh Salari21Endocrine and Metabolism Research Center (Firouzgar, Hemmat Campus, Tehran University of Medical Sciences, Tehran, Iran, 2Scientific Students Research Committee, Tehran University of Medical Sciences, Tehran, IranBackground: The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications.Methods: The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL, high density lipoprotein (HDL, total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm³ and high (>7000/mm³; and then analyzed by Student's t-test or Mann–Whitney U-test as appropriate.Results: The average leukocyte count in these patients was 7594 ± 1965/mm³. Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001. According to this analysis, a leukocyte count of 6750/mm³ with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm³ with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication.Conclusion: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.Keywords: leukocytes, diabetes complications, inflammation

  14. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

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    Pacifico, Lucia; Bonci, Enea; Andreoli, Gian Marco; Di Martino, Michele; Gallozzi, Alessia; De Luca, Ester; Chiesa, Claudio

    2016-01-01

    The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease. PMID:27472326

  15. Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition Hipertensão persistente e lesão renal progressiva induzidas por sobrecarga de sal após inibição temporária do óxido nítrico

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    Ana Lúcia Mattar

    2007-01-01

    Full Text Available INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME and a high-salt diet (HS promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF or the AT-1 receptor blocker losartan (L. Adult male Munich-Wistar rats received NAME and HS. A control Group (C received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ. Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME, um inibidor da produção de NO, com dieta rica

  16. Determination of glomerular filtration rate in patients with early diabetic nephropathy%早期糖尿病肾病患者肾小球滤过率测定

    Institute of Scientific and Technical Information of China (English)

    朱巧红

    2015-01-01

    Objective To investigate the effect of the determination of glomerular filtration rate in treatment of early diabetic nephropathy.Methods Patients with early diabetic nephropathy and normal in our hospital from January 2012 to January 2014 were selected as a medical study,and divided into an early diabetes group and a normal group,30 cases in each group.The glomerular filtration rate between the two groups were determined and compared. Results GFR average index in normal albuminuria group and microalbuminuria group was higher than that in normal group, and difference in the two group compared with the normal group was significant (P<0.05);A large number of albuminuria GFR index was lower than that in the normal group,with significant difference (P<0.05);With UAER,diabetic patients with elevated BUN,Cr,and only a large number of albuminuria group of patients with BUN,Cr significant difference compared with the normal group (P<0.05). Conclusion Using the determination of glomerular filtration rate for early check in diabetic patients,the result can accurately reflect the status of early diabetic nephropathy in patients with renal damage,so as to provide reference for clinical treatment,is worthy of clinical application.%目的:探讨肾小球滤过率测定对早期糖尿病肾病患者治疗的作用。方法选取2012年1月~2014年1月我院收治的早期糖尿病肾病患者以及在此期间来我院进行体检的正常人为研究对象。分为早期糖尿病组与正常组,每组各30例;同时对两组进行肾小球滤过率测定,比较两组的肾小球滤过率。结果正常白蛋白尿组、微量白蛋白尿组的GFR高于正常组平均指标,且两者与正常组相比差异有统计学意义(P<0.05);大量白蛋白尿组的GFR指标低于正常组,两者相比差异有统计学意义(P<0.05);随UAER的增多,糖尿病患者的BUN、Cr升高,且只有大量白蛋白尿组患者的BUN、Cr与正常组相比

  17. Practical prediction model for the risk of 2-year mortality of individuals in the general population.

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    Goldfarb-Rumyantzev, Alexander; Gautam, Shiva; Brown, Robert S

    2016-04-01

    This study proposed to validate a prediction model and risk-stratification tool of 2-year mortality rates of individuals in the general population suitable for office practice use. A risk indicator (R) derived from data in the literature was based on only 6 variables: to calculate R for an individual, starting with 0, for each year of age above 60, add 0.14; for a male, add 0.9; for diabetes mellitus, add 0.7; for albuminuria > 30 mg/g of creatinine, add 0.7; for stage ≥ 3 chronic kidney disease (CKD), add 0.9; for cardiovascular disease (CVD), add 1.4; or for both CKD and CVD, add 1.7. We developed a univariate logistic regression model predicting 2-year individual mortality rates. The National Health and Nutrition Examination Survey (NHANES) data set (1999-2004 with deaths through 2006) was used as the target for validation. These 12,515 subjects had a mean age of 48.9 ± 18.1 years, 48% males, 9.5% diabetes, 11.7% albuminuria, 6.8% CVD, 5.4% CKD, and 2.8% both CKD and CVD. Using the risk indicator R alone to predict mortality demonstrated good performance with area under the receiver operating characteristic (ROC) curve of 0.84. Dividing subjects into low-risk (R=0-1.0), low intermediate risk (R > 1.0-3.0), high intermediate risk (R > 3.0-5.0) or high-risk (R > 5.0) categories predicted 2-year mortality rates of 0.52%, 1.44%, 5.19% and 15.24%, respectively, by the prediction model compared with actual mortality rates of 0.29%, 2.48%, 5.13% and 13.40%, respectively. We have validated a model of risk stratification using easily identified clinical characteristics to predict 2-year mortality rates of individuals in the general population. The model demonstrated performance adequate for its potential use for clinical practice and research decisions.

  18. Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL/6 mice.

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    Romain Dissard

    Full Text Available Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD. C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat and drinking water enriched with fructose (30%. Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418 together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217 but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.

  19. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

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    Murea Mariana

    2012-11-01

    Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

  20. Prevalence of diminished kidney function in a representative sample of middle and older age adults in the Irish population

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    Browne Gemma M

    2012-11-01

    Full Text Available Abstract Background The prevalence of chronic kidney disease (CKD using available estimating equations with the Republic of Ireland is unknown. Methods A randomly selected population based cross-sectional study of 1,098 adults aged 45 years and older was conducted using data from the 2007 Survey of Lifestyle, Attitudes and Nutrition (SLÁN. Estimated Glomerular Filtration Rate (eGFR was calculated from a single IDMS aligned serum creatinine using the CKD-EPI and the MDRD equations, and albumin to creatinine ratio was based on a single random urine sample. Results The sample clinical characteristics and demography was similar to middle and older age adults in the general Irish population, though with an underrepresentation of subjects >75 years and of males. All results are based on subjects with available blood and urine samples. Applying weighting to obtain survey based population estimates, using Irish population census data, the estimated weighted prevalence of CKD-EPI eGFR2 was 11.6%, (95% confidence interval; 9.0, 14.2%, 12.0% ( 9.0, 14.2% of men and 11.2% (7.3, 15.2% of women. Unweighted prevalence estimates were similar at 11.8% (9.9, 13.8%. Albuminuria increased with lower CKD-EPI eGFR category. 10.1% of all subjects had albuminuria and an eGFR≥60 mL/min/1.73 m2 giving an overall weighted estimated prevalence of National Kidney Foundation (NKF defined CKD 21.3% (18.0, 24.6%, with the unadjusted estimate of 21.9% (19.5, 24.4%. MDRD related estimates for eGFR 2, and NFK defined CKD were higher than CKD-EPI and differences were greater in younger and female subjects. Conclusions CKD is highly prevalent in middle and older aged adults within the Republic of Ireland. In this population, there is poor agreement between CKD-EPI and MDRD equations especially at higher GFRs. CKD is associated with lower educational status and poor self rated health.

  1. Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study

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    Hofsø Dag

    2010-04-01

    Full Text Available Abstract Background Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome. Serum creatinine may serve as a surrogate marker of muscle mass, and a possible relationship between low serum creatinine and type 2 diabetes has recently been demonstrated. We aimed to validate this finding in a population of Caucasian morbidly obese subjects. Methods Cross-sectional study of 1,017 consecutive morbidly obese patients with an estimated glomerular filtration rate >60 ml/min/1.73 m2. Logistic regression (univariate and multiple was used to assess the association between serum creatinine and prevalent type 2 diabetes, including statistically testing for the possibility of non-linearity in the relationship by implementation of Generalized Additive Models (GAM and piecewise linear regression. Possible confounding variables such as age, family history of diabetes, waist-to-hip ratio, hypertension, current smoking, serum magnesium, albuminuria and insulin resistance (log HOMA-IR were adjusted for in three separate multiple logistic regression models. Results The unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 μmol/l increase in serum creatinine was associated with 6% (95% CI; 3%-8% and 7% (95% CI; 2%-13% lower odds of diabetes below serum creatinine levels of 69 and 72 μmol/l in women and men, respectively. Above these breakpoints the serum creatinine concentrations did not reduce the odds further. Adjustments for non-modifiable and modifiable risk factors left the piecewise effect for both women and men largely unchanged. In the fully adjusted model, which includes serum magnesium, albuminuria and log HOMA-IR, the piecewise effect for men was statistically non-significant, but it remained present for women. Patients with creatinine levels below median had approximately 50% (women and 75% (men increased odds of diabetes. Conclusions Low serum creatinine is a

  2. Associations between renal hyperfiltration and serum alkaline phosphatase.

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    Se Won Oh

    Full Text Available Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP level is also elevated in patients with diabetes (DM or metabolic syndrome (MS, and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in the Korea National Health and Nutrition Examination Survey IV-V databases (2008-2011 was performed. Renal hyperfiltration was defined as exceeding the age- and sex-specific 97.5th percentile. We divided participants into 4 groups according to their estimated glomerular filtration rate (eGFR: >120, 90-119, 60-89, and 120 mL/min/1.73 m2 showed the highest risk for MS, in the highest ALP quartiles (3.848, 95% CI, 1.876-7.892, compared to the lowest quartile. Similarly, the highest risk for DM, in the highest ALP quartiles, was observed in participants with eGFR >120 ml/min/1.73 m2 (2.166, 95% CI, 1.084-4.329. ALP quartiles were significantly associated with albuminuria in participants with eGFR ≥ 60 ml/min/1.73m2. The highest ALP quartile had a 1.631-fold risk elevation for albuminuria with adjustment of age and sex. (95% CI, 1.158-2.297, P = 0.005. After adjustment, the highest ALP quartile had a 1.624-fold risk elevation, for renal hyperfiltration (95% CI, 1.204-2.192, P = 0.002. In addition, hyperfiltration was significantly associated with hemoglobin, triglyceride, white blood cell count, DM, smoking, and alcohol consumption (P<0.05. The relationship between serum ALP and metabolic disorders is stronger in participants with an upper-normal range of eGFR. Higher ALP levels are significantly associated with renal hyperfiltration in Korean general population.

  3. Urinary albumin excretion rate is correlated with severity of coronary artery disease in elderly type 2 diabetic patients

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    GUO Li-xin; MA Jing; CHENG Yang; ZHANG Li-na; LI Ming

    2012-01-01

    Background Coronary heart disease is the main complication of type 2 diabetes mellitus; its incidence is closely related to microalbuminuria.The aim of this study was to investigate the correlation between the urinary albumin excretion rate and the incidence and severity of coronary heart disease in elderly type 2 diabetes mellitus patients.Methods A total of 612 hospitalized type 2 diabetes mellitus patients aged 60 years or older,who were given coronary angiography for diagnosis of possible coronary heart disease,participated.Their urinary albumin excretion rate was measured,and the severity of coronary artery stenosis was quantified with the Gensini scoring system to analyze the incidence of coronary heart disease and the severity of coronary artery stenosis.The optimal urinary albumin excretion rate predictive value for coronary heart disease incidence in elderly type 2 diabetes mellitus patients was determined.Results The incidence of coronary heart disease,the number of patients with coronary vascular disease and the Gensini scores were significantly different between the microalbuminuria group and the normal albuminuria group (P <0.05).The urinary albumin excretion rate was independently correlated with the occurrence of coronary heart disease in elderly type 2 diabetes mellitus patients (odds ratio (OR) =1.058,P <0.0001,95% confidence interval (CI): 1.036-1.080).Urinary albumin excretion rate and the Gensini score were independently correlated in elderly type 2 diabetes mellitus patients (β=0.476,P <0.0001).The best predictive value of urinary albumin excretion rate was 10.45 μg/min for elderly type 2 diabetes mellitus patients.The area under the curve was 0.764,with a sensitivity and specificity of 70.0% and 72.2%,respectively.Conclusions The occurrence of coronary heart disease in elderly type 2 diabetes mellitus patients with microalbuminuria was higher than that in patients with normal albuminuria,and the severity of the disease also

  4. Silent myocardial infarction in women with type II diabetes mellitus and microalbuminuria

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    Elmir Omerovic

    2008-09-01

    Full Text Available Elmir Omerovic, Gerhard Brohall, Markus Müller, Truls Råmunddal, Göran Matejka, Finn Waagstein, Björn FagerbergThe Wallenburg Laboratory at Sahlgrenska Academy, Department of Cardiology, Sahlgrenska University Hospital, Gothenburg University, 413 45, Gothenburg, Sweden; Department of Cardiology and Department of Radiology, Sahlgrenska University Hospital, Gothenburg, SwedenIntroduction: The aim of this study was to investigate whether asymptomatic women with diabetes mellitus (DM without previous history of ischemic heart disease (IHD and normal electrocardiogram (ECG have suffered silent myocardial infarction (MI.Methods: The study population consisted of 64-years old women with DM and albuminuria (n = 15 and aged- and body mass index-matched controls (n = 16. The patients were selected after screening of 240 women with previously known or unknown DM. The individuals with previous history of IHD and ECG suggesting the presence of IHD were excluded. All subjects were investigated with magnetic resonance imaging (MRI.Results: MRI investigation has revealed the presence of subendocardial MI in the two DM women (13%. No MI was detected in the control group. MR coronary angiography detected the presence of significant stenosis in the proximal segment of left anterior descending (LAD coronary artery in one DM woman. This patient developed unstable angina 1 week after the MRI investigation. The conventional angiography has confirmed the presence of significant stenosis in LAD demanding invasive revascularization by percutaneous coronary angioplasty. No difference was found in indices of left ventricular (LV systolic function while diastolic function was disturbed in the DM group. There was a tendency for increased LV mass in the DM group. No difference was found in the LV volumes.Conclusion: Clinically significant proportion of the women with DM and albuminuria without previous history of IHD have had silent MI. MRI screening of these high risk

  5. Cardiorenal syndrome in patients with chronic kidney disease and diabetes mellitus

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    Irina Mikhaylovna Kutyrina

    2013-11-01

    Full Text Available Aim. Combination of cardiovascular and renal disease is currently viewed as a unified cardiorenal syndrome (CRS. The aim of our study was to assess the CRS prevalence and risk factors associated with left ventricular hypertrophy (LVH in patients with pre-dialysis stages of chronic kidney disease (CKD of various etiology.Materials and Methods. We enrolled 172 patients with CKD to participate in this study. First group consisted of 83 patients with nondiabetic CKD at 2nd through 4th stage (mean age 46±15 years, 51% male and 29% female. Mean glomerular filtration rate (GFR was 37.2 ml/min (33.9–41.4 with 95% CI; creatinine plasma clearance was 2.9 mg/dl (2.6–3.2. Second group consisted of 89 patients with type 2 diabetes mellitus (T2DM and CKD at 1st–2nd stage (40% male and 60% female with albuminuria (mean age 57.3±7.1 years. Duration of diabetes in this sampling was 10.4±7.1 years. All patients underwent standard clinical examination, supplemented with echocardiography to evaluate the influence of general and CKD-related risk factors for LVH.Results. LVH was diagnosed in 37.3% of non-diabetic patients with CKD at 2nd through 4th stage. Aside from classic cardiovascular risk factors (including age, gender, arterial hypertension, family history of cardiovascular diseases, hypercholesterolemia, we observed the impact of kidney-related factors (anemia, plasma creatinine, disturbance of calcium-phosphorus metabolism. CKD progression was associated with elevation in the incidence of concentric and eccentric LVH. Patients with T2DM were diagnosed with LVH in 36% of cases. Increased myocardial mass correlated with plasma levels of uric acid, HbA1c, obesity and albuminuria. There was also a firm association between diabetic nephropathy, left ventricular myocardial remodelling and a history of cardiovascular events.Conclusion: In patients with diabetes mellitus and CKD cardiorenal syndrome develops at pre-dialysis stages due to both

  6. Induction of heme oxygenase-1 can halt and even reverse renal tubule-interstitial fibrosis.

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    Matheus Correa-Costa

    Full Text Available BACKGROUND: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1 is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. AIM: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. METHODS: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. RESULTS: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-β protein production was significantly lower in Hemin-treated animals. CONCLUSION: Treatment with Hemin was able both to prevent the progression of fibrosis and

  7. Long term metabolic syndrome induced by a high fat high fructose diet leads to minimal renal injury in C57BL/6 mice.

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    Dissard, Romain; Klein, Julie; Caubet, Cécile; Breuil, Benjamin; Siwy, Justyna; Hoffman, Janosch; Sicard, Laurent; Ducassé, Laure; Rascalou, Simon; Payre, Bruno; Buléon, Marie; Mullen, William; Mischak, Harald; Tack, Ivan; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

    2013-01-01

    Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.

  8. Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes

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    Nagaishi, Kanna; Mizue, Yuka; Chikenji, Takako; Otani, Miho; Nakano, Masako; Konari, Naoto; Fujimiya, Mineko

    2016-01-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have contributed to the improvement of diabetic nephropathy (DN); however, the actual mediator of this effect and its role has not been characterized thoroughly. We investigated the effects of MSC therapy on DN, focusing on the paracrine effect of renal trophic factors, including exosomes secreted by MSCs. MSCs and MSC-conditioned medium (MSC-CM) as renal trophic factors were administered in parallel to high-fat diet (HFD)-induced type 2 diabetic mice and streptozotocin (STZ)-induced insulin-deficient diabetic mice. Both therapies showed approximately equivalent curative effects, as each inhibited the exacerbation of albuminuria. They also suppressed the excessive infiltration of BMDCs into the kidney by regulating the expression of the adhesion molecule ICAM-1. Proinflammatory cytokine expression (e.g., TNF-α) and fibrosis in tubular interstitium were inhibited. TGF-β1 expression was down-regulated and tight junction protein expression (e.g., ZO-1) was maintained, which sequentially suppressed the epithelial-to-mesenchymal transition of tubular epithelial cells (TECs). Exosomes purified from MSC-CM exerted an anti-apoptotic effect and protected tight junction structure in TECs. The increase of glomerular mesangium substrate was inhibited in HFD-diabetic mice. MSC therapy is a promising tool to prevent DN via the paracrine effect of renal trophic factors including exosomes due to its multifactorial action. PMID:27721418

  9. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

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    Jang Hyun Koh

    2014-01-01

    Full Text Available The overexpression of vascular endothelial growth factor (VEGF is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10, OLETF rats as diabetic control group (n=10, and OLETF rats treated with taurine group (n=10. We treated taurine (200 mg/kg/day for 20 weeks and treated high glucose (HG, 30 mM with or without taurine (30 mM in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

  10. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

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    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders

  11. Mammographically detected breast arterial calcifications: Indicators for arteriosclerotic diseases?

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    Purpose: To determine the prevalence of breast arterial calcifications (BAC) detected on mammography and search for conditions that may influence their existence. Materials and methods: The mammograms of 6156 consecutive patients were reevaluated for the presence of BAC. Four hundred eighty-five women having BAC were enrolled in the patient group. Additionally, randomly selected 500 women, without BAC constituted the control group. Hospital records of the participants were reviewed for parity, menopausal status, oral contraceptive agent (OCA) usage, hormone replacement therapy (HRT) usage, presence of diabetes, hypertension, hyperlipidemia, albuminuria and history of myocardial infarction (MI). Results: Prevalence of BAC was 7.9% on mammograms. Ninety-four women were aged between 40 and 49 years, 165 were aged between 50 and 59 years and 226 were over 60 years among BAC positive 485 women. A significant relationship was found for the frequency of BAC versus age and HRT usage in all age groups (p 0.05). Conclusion: Most benign findings like BAC are not routinely reported during mammographic evaluation. Our study showed that, presence of BAC on mammography was strongly related to advancing age. However, these findings may signify a systemic risk and can be used as precautious indicators for undocumented systemic diseases, especially in premenopausal women

  12. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

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    Gluhovschi, Gheorghe; Petrica, Ligia; Timar, Romulus; Velciov, Silvia; Ionita, Ioana; Kaycsa, Adriana; Timar, Bogdan

    2016-01-01

    Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

  13. Effect of the Direct Renin Inhibitor Aliskiren on Urinary Albumin Excretion in Spontaneous Type 2 Diabetic KK- Mouse

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    Masako Furukawa

    2013-01-01

    Full Text Available Objective. Although angiotensin II-mediated inflammation and extracellular matrix accumulation are considered to be associated with the progression of diabetic nephropathy, these processes have not yet been sufficiently clarified. The objective of this study was to determine whether the correction of the abnormal renal expression of MMPs and its inhibitors (MMPs/TIMPs and cytokines following the administration of aliskiren to KK- mice results in a renoprotective effect. Methods. KK- mice were divided into two groups, that is, untreated (saline and treated (aliskiren groups. Systolic BP, HbA1c levels, and the albumin-creatinine ratio (ACR were measured. The renal expression of MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (prorenin receptor ((PRR was examined using real-time PCR and/or immunohistochemical staining. Renal MAPK and NF-κB activity were also examined by Western blot analyses and ELISA, respectively. Results. Significant decreases in systolic BP and ACR levels were observed in treated KK- mice compared with the findings in untreated KK- mice. Furthermore, increases in MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (PRR expression, in addition to MAPK and NF-κB activity, were significantly attenuated by aliskiren administration. Conclusions. It appears that aliskiren improves albuminuria and renal fibrosis by regulating inflammation and the alteration of collagen synthesis and degradation.

  14. Effect of the Direct Renin Inhibitor Aliskiren on Urinary Albumin Excretion in Spontaneous Type 2 Diabetic KK-A (y) Mouse.

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    Furukawa, Masako; Gohda, Tomohito; Hagiwara, Shinji; Tanimoto, Mitsuo; Horikoshi, Satoshi; Funabiki, Kazuhiko; Tomino, Yasuhiko

    2013-01-01

    Objective. Although angiotensin II-mediated inflammation and extracellular matrix accumulation are considered to be associated with the progression of diabetic nephropathy, these processes have not yet been sufficiently clarified. The objective of this study was to determine whether the correction of the abnormal renal expression of MMPs and its inhibitors (MMPs/TIMPs) and cytokines following the administration of aliskiren to KK-A (y) mice results in a renoprotective effect. Methods. KK-A (y) mice were divided into two groups, that is, untreated (saline) and treated (aliskiren) groups. Systolic BP, HbA1c levels, and the albumin-creatinine ratio (ACR) were measured. The renal expression of MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (pro)renin receptor ((P)RR) was examined using real-time PCR and/or immunohistochemical staining. Renal MAPK and NF- κ B activity were also examined by Western blot analyses and ELISA, respectively. Results. Significant decreases in systolic BP and ACR levels were observed in treated KK-A (y) mice compared with the findings in untreated KK-A (y) mice. Furthermore, increases in MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (P)RR expression, in addition to MAPK and NF- κ B activity, were significantly attenuated by aliskiren administration. Conclusions. It appears that aliskiren improves albuminuria and renal fibrosis by regulating inflammation and the alteration of collagen synthesis and degradation. PMID:23819050

  15. Effect of the Direct Renin Inhibitor Aliskiren on Urinary Albumin Excretion in Spontaneous Type 2 Diabetic KK-Ay Mouse

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    Furukawa, Masako; Horikoshi, Satoshi; Funabiki, Kazuhiko; Tomino, Yasuhiko

    2013-01-01

    Objective. Although angiotensin II-mediated inflammation and extracellular matrix accumulation are considered to be associated with the progression of diabetic nephropathy, these processes have not yet been sufficiently clarified. The objective of this study was to determine whether the correction of the abnormal renal expression of MMPs and its inhibitors (MMPs/TIMPs) and cytokines following the administration of aliskiren to KK-Ay mice results in a renoprotective effect. Methods. KK-Ay mice were divided into two groups, that is, untreated (saline) and treated (aliskiren) groups. Systolic BP, HbA1c levels, and the albumin-creatinine ratio (ACR) were measured. The renal expression of MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (pro)renin receptor ((P)RR) was examined using real-time PCR and/or immunohistochemical staining. Renal MAPK and NF-κB activity were also examined by Western blot analyses and ELISA, respectively. Results. Significant decreases in systolic BP and ACR levels were observed in treated KK-Ay mice compared with the findings in untreated KK-Ay mice. Furthermore, increases in MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (P)RR expression, in addition to MAPK and NF-κB activity, were significantly attenuated by aliskiren administration. Conclusions. It appears that aliskiren improves albuminuria and renal fibrosis by regulating inflammation and the alteration of collagen synthesis and degradation. PMID:23819050

  16. Early detection of diabetic kidney disease: Present limitations and future perspectives.

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    Lin, Chih-Hung; Chang, Yi-Cheng; Chuang, Lee-Ming

    2016-07-25

    Diabetic kidney disease (DKD) is one of the most common diabetic complications, as well as the leading cause of chronic kidney disease and end-stage renal disease around the world. To prevent the dreadful consequence, development of new assays for diagnostic of DKD has always been the priority in the research field of diabetic complications. At present, urinary albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) are the standard methods for assessing glomerular damage and renal function changes in clinical practice. However, due to diverse tissue involvement in different individuals, the so-called "non-albuminuric renal impairment" is not uncommon, especially in patients with type 2 diabetes. On the other hand, the precision of creatinine-based GFR estimates is limited in hyperfiltration status. These facts make albuminuria and eGFR less reliable indicators for early-stage DKD. In recent years, considerable progress has been made in the understanding of the pathogenesis of DKD, along with the elucidation of its genetic profiles and phenotypic expression of different molecules. With the help of ever-evolving technologies, it has gradually become plausible to apply the thriving information in clinical practice. The strength and weakness of several novel biomarkers, genomic, proteomic and metabolomic signatures in assisting the early diagnosis of DKD will be discussed in this article. PMID:27525056

  17. GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.

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    Giacco, Ferdinando; Du, Xueliang; Carratú, Anna; Gerfen, Gary J; D'Apolito, Maria; Giardino, Ida; Rasola, Andrea; Marin, Oriano; Divakaruni, Ajit S; Murphy, Anne N; Shah, Manasi S; Brownlee, Michael

    2015-09-01

    The assumption underlying current diabetes treatment is that lowering the level of time-averaged glucose concentrations, measured as HbA1c, prevents microvascular complications. However, 89% of variation in risk of retinopathy, microalbuminuria, or albuminuria is due to elements of glycemia not captured by mean HbA1c values. We show that transient exposure to high glucose activates a multicomponent feedback loop that causes a stable left shift of the glucose concentration-reactive oxygen species (ROS) dose-response curve. Feedback loop disruption by the GLP-1 cleavage product GLP-1(9-36)(amide) reverses the persistent left shift, thereby normalizing persistent overproduction of ROS and its pathophysiologic consequences. These data suggest that hyperglycemic spikes high enough to activate persistent ROS production during subsequent periods of normal glycemia but too brief to affect the HbA1c value are a major determinant of the 89% of diabetes complications risk not captured by HbA1c. The phenomenon and mechanism described in this study provide a basis for the development of both new biomarkers to complement HbA1c and novel therapeutic agents, including GLP-1(9-36)(amide), for the prevention and treatment of diabetes complications.

  18. Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study

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    Aramsaowapak, Kasemsan; Tangwonglert, Theerasak; Supasyndh, Ouppatham

    2016-01-01

    Background. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. Methods. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline. Results. Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64–0.79, for UANG of 0.71; 95% CI 0.63–0.79, for UNGAL of 0.64; 95% CI 0.56–0.72, and for UKIM-1 of 0.71; 95% CI 0.63–0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles. Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function. PMID:27672664

  19. Astragaloside IV ameliorates renal injury in db/db mice

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    Sun, Huili; Wang, Wenjing; Han, Pengxun; Shao, Mumin; Song, Gaofeng; Du, Heng; Yi, Tiegang; Li, Shunmin

    2016-09-01

    Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.

  20. [Assessment of renal function, iatrogenic hyperkalemia and acute renal dysfunction in cardiology. Contrast-induced nephropathy].

    Science.gov (United States)

    Górriz Teruel, José Luis; Beltrán Catalán, Sandra

    2011-12-01

    Renal impairment influences the prognosis of patients with cardiovascular disease and increases cardiovascular risk. Renal dysfunction is a marker of lesions in other parts of the vascular tree and detection facilitates early identification of individuals at high risk of cardiovascular events. In patients with cardiovascular disease, renal function is assessed by measuring albuminuria in a spot urine sample and by estimating the glomerular filtration rate using creatinine-derived predictive formulas or equations. We recommend the Chronic Kidney Disease Epidemiology Collaboration or the Modification of Diet in Renal Disease formulas. The Cockcroft-Gault formula is a possible alternative. The administration of drugs that block the angiotensin-renin system can, on occasion, be associated with acute renal dysfunction or hyperkalemia. We need to know when risk of these complications exists so as to provide the best possible treatment: prevention. Given the growing number of diagnostic and therapeutic procedures in the field of cardiology that use intravenous contrast media, contrast-induced nephrotoxicity represents a significant problem. We should identify the risk factors and patients at greatest risk, and prevent it from appearing.

  1. Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.

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    Laczy, Boglárka; Cseh, Judit; Mohás, Márton; Markó, Lajos; Tamaskó, Mónika; Koszegi, Tamás; Molnár, Gergo A; Wagner, Zoltán; Wagner, László; Wittmann, István

    2009-06-01

    Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients. PMID:18839054

  2. ANTIHYPERGLYCEMIC ACTIVITY OF Exacum wightianum Arn. AN ENDEMIC MEDICINAL PLANT.

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    Madathupatti Ramanathan Udhayasankar

    2012-07-01

    Full Text Available An attempt was made to study the beneficial effects of ethanol extract of Exacum wightianum Arn. (Gentianaceae on its antihyperglycemic activity in streptozotocin induced diabetic rats. The pilot studies were carried after oral administration at doses of ethanolic extract of E. wightianum 100, 200, 500 and 1000 mg/kgb.wt. in sub-acute study. In diabetic induced rats fed with E. wightianum ethanol extract at 100 and 200 mg/kg body b.wt., the fasting plasma glucose levels were reduced to normal body and liver weight were found to be increased. Where as blood glucose, protein, albumin and creatinine levels were estimated after two weeks. Theextract significantly inhibited the induction of albuminuria, proteinemia and uremia. The present study clearly indicated a significant antidiabetic activity with the ethanol extract of E. wightianum supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Also the extract is useful in preventing the incidence of long term complications of diabetes mellitus.

  3. Renal function in diabetic nephropathy.

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    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  4. Sequential and functional renal scintiscanning in diabetic and hypertensive patients

    International Nuclear Information System (INIS)

    47 diabetics (94 kidneys), 30 diabetics with concurrent hypertension (60 kidneys), and 23 hypertensives (46 kidneys) were examined by renal serial functional scintiscanning with 131I-ortho-iodo-hippuric acid. For evaluation, camera nephrographs of the whole kidney, renal hemispheres, and renal cortex were used according to the technique of 'regions of interest', and the parameters of secretory value, maximum secretion, and elimination half-life were determined on this basis. With regard to the extent of hypertension, there are significant differences between all three groups for the elimination half-life; as far as the secretory value was concerned, there was a difference between the group with high hypertension and the two other groups. Significant differences in secretory value and elimination half-life were also observed in hypertensives with and without changes in the fundus of the eye. There was no noticeable difference between the three parameters in groups with and without albuminuria. (orig./AJ) 891 AJ/orig.- 892 MKO

  5. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

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    Viazzi, Francesca; Bonino, Barbara; Cappadona, Francesca; Pontremoli, Roberto

    2016-08-01

    The Renin-Angiotensin-Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition. PMID:26984204

  6. Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.

    Science.gov (United States)

    Laczy, Boglárka; Cseh, Judit; Mohás, Márton; Markó, Lajos; Tamaskó, Mónika; Koszegi, Tamás; Molnár, Gergo A; Wagner, Zoltán; Wagner, László; Wittmann, István

    2009-06-01

    Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.

  7. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

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    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-06-01

    Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  8. [Comparison of treatment principles of elderly hypertensive patients with different cardiovascular risks based on Hungarian and international guidelines (2001-2015)].

    Science.gov (United States)

    Bödör, Anikó; Kiss, István

    2016-02-14

    The aim of this review is to present recommendations of the currently valid Hungarian practice guidelines regarding antihypertensive therapy of the elderly and very elderly with different cardiovascular risk profiles, compare and contrast these with international guidelines, describe changes brought about by the past 15 years, and review the evidence behind. Hypertension treatment guidelines and relevant statements of the Hungarian and European Societies of Hypertension, of the Joint National Committee and American Heart Association were processed. The use of age-independent treatment threshold, goal blood pressure values, and the tendency towards more intensive control in co-morbidities conferring high cardiovascular risk were overcome by the upsurge of new evidence and the re-evaluation of previous clinical trial data. These lead to the introduction of age-specific and generally less stringent blood pressure targets in all regions compared. However, the guidelines currently in force still differ in terms of the attainable values in concomitant diabetes, chronic kidney disease or albuminuria, use of beta-blockers and the definition of elderly. Nevertheless, there is unanimous agreement that benefit from lowering of blood pressure under systolic 140 mmHg is not supported by evidence and further investigation is warranted to determine optimal treatment targets in the elderly, in the aged over 80 and specific elderly risk groups.

  9. Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia.

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    Eugene Han

    Full Text Available Beneficial effects of omega-3 fatty acid (O3FA supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD, especially in diabetic nephropathy (DN with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR and glomerular filtrate rate (GFR were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0% patients did not experience renal function loss, and 125 (36.3% patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001. This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.

  10. Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats

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    Chungang Liu

    2016-01-01

    Full Text Available Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM in diet-streptozotocin- (STZ- induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-β-d-glucosaminidase verified CM’s renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3β in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats.

  11. Oral immunotherapy of recurrent urinary tract infections: a double-blind placebo-controlled multicenter study.

    Science.gov (United States)

    Schulman, C C; Corbusier, A; Michiels, H; Taenzer, H J

    1993-09-01

    We treated 166 patients suffering from recurrent urinary tract infections under double-blind conditions for 3 months with 1 capsule daily of either the immunostimulating bacterial extract (85) or a placebo (81), followed by a 3-month observation period without the test drugs. The bacterial extract exerted a significant beneficial curative action and long-term consolidative effect on the frequency of recurrent urinary tract infections with marked improvements in the characteristic signs and symptoms. It was significantly superior to placebo for the majority of the assessed parameters: number of recurrent urinary tract infections, bacteriuria, leukocyturia, erythrocyturia, nitrituria, albuminuria and casts in urine. Consumption of antibiotics, chemotherapeutics, urinary antiseptics or disinfectants was significantly less under active drug therapy compared to placebo. Tolerance was good with only 2 side effects reported in 2 patients (2%) in the active group compared to 11 among 5 (6%) in the placebo group. Therefore, the bacterial extract can be considered an efficient and well tolerated drug for the treatment of urinary tract infections, and their accompanying signs and symptoms, as well as for decreasing the risk of recurrences and the need for antibiotics and other antibacterial drugs.

  12. Glomerular endothelial surface layer acts as a barrier against albumin filtration.

    Science.gov (United States)

    Dane, Martijn J C; van den Berg, Bernard M; Avramut, M Cristina; Faas, Frank G A; van der Vlag, Johan; Rops, Angelique L W M M; Ravelli, Raimond B G; Koster, Bram J; van Zonneveld, Anton Jan; Vink, Hans; Rabelink, Ton J

    2013-05-01

    Glomerular endothelium is highly fenestrated, and its contribution to glomerular barrier function is the subject of debate. In recent years, a polysaccharide-rich endothelial surface layer (ESL) has been postulated to act as a filtration barrier for large molecules, such as albumin. To test this hypothesis, we disturbed the ESL in C57Bl/6 mice using long-term hyaluronidase infusion for 4 weeks and monitored albumin passage using immunolabeling and correlative light-electron microscopy that allows for complete and integral assessment of glomerular albumin passage. ESL ultrastructure was visualized by transmission electron microscopy using cupromeronic blue and by localization of ESL binding lectins using confocal microscopy. We demonstrate that glomerular fenestrae are filled with dense negatively charged polysaccharide structures that are largely removed in the presence of circulating hyaluronidase, leaving the polysaccharide surfaces of other glomerular cells intact. Both retention of native ferritin [corrected] in the glomerular basement membrane and systemic blood pressure were unaltered. Enzyme treatment, however, induced albumin passage across the endothelium in 90% of glomeruli, whereas this could not be observed in controls. Yet, there was no net albuminuria due to binding and uptake of filtered albumin by the podocytes and parietal epithelium. ESL structure and function completely recovered within 4 weeks on cessation of hyaluronidase infusion. Thus, the polyanionic ESL component, hyaluronan, is a key component of the glomerular endothelial protein permeability barrier.

  13. Lower Plasma Creatinine and Urine Albumin in Individuals at Increased Risk of Type 2 Diabetes with Factor V Leiden Mutation

    Science.gov (United States)

    Fritsche, Andreas; Machicao, Fausto; Nawroth, Peter P.; Häring, Hans-Ulrich; Isermann, Berend

    2014-01-01

    The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P = 0.03) and tended to have lower plasma creatinine concentrations (P = 0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P = 0.048). These observations at a very early “disease” stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies. PMID:24729885

  14. Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

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    Machado Ubiratan F

    2011-04-01

    Full Text Available Abstract Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2 in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP and heart rate variability (spectral analysis one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting. Results Higher glycemia (p vs. nondiabetics (p vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

  15. Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats.

    Science.gov (United States)

    Ma, Song-Tao; Liu, Dong-lian; Deng, Jing-jing; Niu, Rui; Liu, Rui-bin

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. PMID:23147865

  16. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.

    Science.gov (United States)

    Piccoli, Giorgina B; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID:26676663

  17. The early modern kidney--nephrology in and about the nineteenth century. Part 1.

    Science.gov (United States)

    Eknoyan, Garabed

    2013-01-01

    The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789-1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816-1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816-1895) and for active tubular transport by Rudolf Heidenhain (1834-1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis). PMID:23278189

  18. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.

    Science.gov (United States)

    Chen, Zhuo; Miao, Feng; Paterson, Andrew D; Lachin, John M; Zhang, Lingxiao; Schones, Dustin E; Wu, Xiwei; Wang, Jinhui; Tompkins, Joshua D; Genuth, Saul; Braffett, Barbara H; Riggs, Arthur D; Natarajan, Rama

    2016-05-24

    We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory. PMID:27162351

  19. Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.

    Science.gov (United States)

    Hale, L J; Welsh, G I; Perks, C M; Hurcombe, J A; Moore, S; Hers, I; Saleem, M A; Mathieson, P W; Murphy, A J; Jeansson, M; Holly, J M; Hardouin, S N; Coward, R J

    2013-05-01

    Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species. PMID:23299523

  20. Medical nutrition therapy in adults with chronic kidney disease: integrating evidence and consensus into practice for the generalist registered dietitian nutritionist.

    Science.gov (United States)

    Beto, Judith A; Ramirez, Wendy E; Bansal, Vinod K

    2014-07-01

    Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature.

  1. LONG-TERM THERAPY WITH INDAPAMIDE IN ELDERLY AND SENILE PATIENTS WITH HYPERTENSION: CARDIORENOPROTECTIVE EFFECTS AND INFLUENCE ON QUALITY OF LIFE

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    M. E. Statsenko

    2009-01-01

    Full Text Available Aim. To estimate cardiorenoprotective effect of 12-month therapy by indapamide in elderly and senile patients with arterial hypertension (HT and its influence on quality of life.Material and methods. 40 elderly and senile patients with HT were examined. 70% of patients received monotherapy by indapamide 2,5 mg once daily and 30% of patients were treated with indapamide and lisinopril combination. Duration of observation was 12 months. Ambulatory blood pressure (BP monitoring, echocardiography, plasma lipid profile, glycemia and uricemia levels and potassium serum level was evaluated initially and after 12 months of therapy. Glomerular filtration rate and albuminuria as well as patient quality of life also was evaluated.Results. Target BP level was reached in all patients during 12 month therapy. Reduction of average 24-hour, day and night BP, BP load, rate of morning BP rising was observed. Negative influence on BP variability was not found. Improvement of daily BP profile also was found. The indapamide reduced left ventricle mass, improved renal function, vessel resistance and quality of life. Negative influence of long-term therapy with indapamide on lipid, glucose, purine metabolism and serum potassium level was not observed.Conclusion. Indapamide is an effective antihypertensive drug for long-term treatment of elderly and senile patients with HT of 1-2 degree.

  2. Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

    2016-09-01

    Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia. PMID:26674759

  3. Evaluation of microalbuminuria in obese children and its relation to metabolic syndrome.

    Science.gov (United States)

    Sanad, Mohammed; Gharib, Amal

    2011-12-01

    Several epidemiologic studies have clearly demonstrated that obesity increases the risk of kidney diseases. We have attempted to evaluate the association of obesity with albuminuria, an early marker of kidney disease, among obese children and its relation to metabolic syndrome. This study included 150 obese children. Blood pressure, fasting blood glucose, plasma insulin and the lipid profile were assessed. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate in vivo insulin resistance. Urinary albumin and creatinine were estimated. Microalbuminuria was detected in 22 (14.7%) of the obese children. Waist circumference, blood pressure, triglyceride, low-density lipoprotein (LDL), insulin resistance and fasting blood glucose were significantly higher in obese children with microalbuminuria than in those with normoalbuminuria and showed significant positive correlations with microalbuminuria. High-density lipoprotein (HDL) was significantly lower in obese children with microalbuminuria than in those with normoalbuminuria, with a significant negative correlation with microalbuminuria. We found that body mass index, abdominal obesity, hypertension, impaired fasting glucose level and insulin resistance significantly increased the odds of microalbuminuria in the obese children enrolled in this study. Moreover, high triglyceride, high LDL and low HDL were significantly associated with microalbuminuria. In our patient group, childhood obesity was a risk factor for the development of microalbuminuria, which in turn was significantly associated with metabolic syndrome and its different constituents. PMID:21638155

  4. Urinary retinol binding protein is a marker of the extent of interstitial kidney fibrosis.

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    Nicolas Pallet

    Full Text Available Currently, a non-invasive method to estimate the degree of interstitial fibrosis (IF in chronic kidney disease is not available in routine. The aim of our study was to evaluate the diagnostic performance of the measurement of urinary low molecular weight (LMW protein concentrations as a method to determine the extent of IF. The urines specimen from 162 consecutive patients who underwent renal biopsy were used in the analysis. Numerical quantification software based on the colorimetric analysis of fibrous areas was used to assess the percentage IF. Total proteinuria, albuminuria, and the urinary levels of retinol binding protein (RBP, alpha1-microglobulin (α1MG, beta 2-microglobulin (β2MG, transferrin, and IgG immunoglobulins were measured. There was a significant correlation between the degree of IF and the RBP/creatinine (creat ratio (R2: 0.11, p25% of the parenchyma was 95% when using a threshold of 20 mg/g creat. In conclusion, RBP appears to be a quantitative and non-invasive marker for the independent prediction of the extent of kidney IF. Because methods for the measurement of urinary RBP are available in most clinical chemistry departments, RBP measurement is appealing for implementation in the routine care of patients with chronic kidney disease.

  5. The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications.

    Science.gov (United States)

    Avogaro, Angelo; Fadini, Gian Paolo

    2014-10-01

    We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: ("diabetes" OR "diabetic") AND ("retinopathy" OR "retinal" OR "nephropathy" OR "renal" OR "albuminuria" OR "microalbuminuria" OR "neuropathy" OR "ulcer" OR "wound" OR "bone marrow"); ("dipeptidyl peptidase-4" OR "dipeptidyl peptidase-IV" OR "DPP-4" OR "DPP-IV"); and ("inhibition" OR "inhibitor"). Experimentally, DPP4-I appears to improve inflammation, endothelial function, blood pressure, lipid metabolism, and bone marrow function. Several experimental studies report direct potential beneficial effects of DPP4-I on all microvascular diabetes-related complications. These drugs have the ability to act either directly or indirectly via improved glucose control, GLP-1 bioavailability, and modifying nonincretin substrates. Although preliminary clinical data support that DPP4-I therapy can protect from microangiopathy, insufficient evidence is available to conclude that this class of drugs directly prevents or decreases microangiopathy in humans independently from improved glucose control. Experimental findings and preliminary clinical data suggest that DPP4-I, in addition to improving metabolic control, have the potential to interfere with the onset and progression of diabetic microangiopathy. Further evidence is needed to confirm these effects in patients with diabetes. PMID:25249673

  6. Biomarkers of Renal Disease and Progression in Patients with Diabetes

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    Radovan Hojs

    2015-05-01

    Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

  7. Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006

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    Sturniolo Antonio

    2010-06-01

    Full Text Available Abstract Background Environmental factors have been associated with the outbreak of chronic kidney disease (CKD. We evaluated the association of Cadmium (Cd exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES. Methods 5426 subjects ≥ 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB after adjustment for age, gender, race/ethnicity, body mass index and smoking habits. Results Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001. Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046 and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007. An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014. Conclusions Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population.

  8. Hypertension in Chronic Glomerulonephritis.

    Science.gov (United States)

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  9. Role of new biomarkers for the diagnosis of nephropathy associated with diabetes type 2.

    Science.gov (United States)

    Żyłka, Agnieszka; Gala-Błądzińska, Agnieszka; Rybak, Katarzyna; Dumnicka, Paulina; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

    2015-01-01

    In twenty first century, the incidence of type 2 diabetes mellitus (DMt2) dramatically increases, followed by the number of patients suffering from its complications. Currently, diabetic kidney disease (DKD) is the leading cause of renal replacement therapy. Often, DMt2 is diagnosed after several years of duration, and irreversible organ damage can develop during that period. On the other hand, the early diag- nosis of DKD in the preclinical phase, when glomerular filtration rate (GFR) is still maintained and there are no evident changes in urinalysis, gives the possibility of implementing the nephroprotective treatment that can significantly delay the progression of the disease. However, the diagnostic tests available in clinical practice, i.e. serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria have important limitations. There is a need for new, early and non-invasive biomarkers specific for kidney injury, allowing for differentiation between glomerular and tubular injury, and changing dynamically in response to the degree of kidney damage. Hereby, we review the current knowledge about the novel and emerging biomarkers of kidney injury and their used for the diagnosis of DKD.

  10. [Management of uncomplicated arterial hypertension in pregnancy].

    Science.gov (United States)

    Gullotti, D; Gullotti, A; Schillaci, L; Lo Genco, A; Figlioli, F; Pira, M; Rotolo, G

    2006-02-01

    In the management of uncomplicated arterial hypertension in pregnancy, blood pressure (BP) values of pregnant women should be treated in order to reduce risks of both maternal and fetal complications. To reduce these risks, it is necessary to monitor BP, some hematochemical parameters and albuminuria, to try to prevent more serious clinical complications. Moreover, repeated measurements of BP, as well as frequent ambulatory blood pressure monitoring (ABPM) over 24 h are necessary. In the treatment of hypertension in pregnancy, if there are no high risks, it is possible to try a non pharmacological antihypertensive therapy consisting of a suitable diet, reduction of weight, abolition of some lifestyles (smoking, excessive alcohol consumption and heavy physical exercises). If these measures are not sufficient or the risk is high, a pharmacological therapy with neither toxic nor teratogenic drugs for the fetus will be administered in order to normalize BP without reducing perfusion of the uterus/placenta. Only in case of severe hypertension, a more aggressive pharmacological treatment should be carried out and, if necessary, hospitalization. The drugs suggested in these cases are those which have already been recognised as presenting low side effects. Antihypertensive drugs used in pregnancy can be classified as: suitable (methyldopa, clonidine, long acting calcioantagonists); cautiously used (alpha-blockers, beta-betablockers); contraindicated (ACE-inhibitors, sartans, short acting calcioantagonists). Hyper-tensive crises should be treated with an injection therapy (clonidine, labetalol), with hospital admission if necessary, or if preeclampsia or eclampsia may occur. PMID:16565702

  11. Perindopril/indapamide combination in the first-line treatment of hypertension and end-organ protection.

    Science.gov (United States)

    Gosse, Philippe

    2006-05-01

    This article examines evidence-based findings in the literature on the efficacy of perindopril 2 mg/indapamide 0.625 mg, a first-line, low-dose antihypertensive drug combination. In regulatory Phase II and III trials, perindopril/indapamide significantly lowered blood pressure compared with other first-line therapies (atenolol, losartan and irbesartan). This was also the case in STRAtegies of Treatment in Hypertension: Evaluation, a postregistration study versus current monotherapies and stepped-care therapy with different classes of antihypertensive agents. The efficacy/safety ratio (both clinical and with regard to laboratory parameters) of perindopril/indapamide was good. Perindopril/indapamide provides additional antihypertensive efficacy compared with each component used alone and with current monotherapies, with major efficacy on systolic blood pressure, an important predictor of cardiovascular risk. It also reduces pulse pressure, an independent cardiovascular risk factor, large-vessel arterial stiffness and microcirculatory alterations. The fixed dosage of a once-daily tablet, ensures optimal ease of use and enhances patient compliance. Perindopril/indapamide also reduces target organ damage in patients at high cardiovascular risk, such as patients with cardiac hypertrophy and Type 2 diabetics with albuminuria. These benefits, together with the good efficacy/tolerability ratio, fulfill the requirements of the European Society of Hypertension and of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines for low-dose, first-line combination therapy in hypertension. PMID:16716093

  12. The Prognosis of Patients with Chronic Kidney Disease and Diabetes Mellitus

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    Vladu Mihaela

    2014-09-01

    Full Text Available Background and Aims: Diabetes mellitus (DM is a chronic disease which can evolve towards devastating micro and macro-vascular complications. Chronic kidney disease (CKD is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD and premature death. The aim of our study was to evaluate the prognosis in patients with DM and CKD, depending on estimated glomerular filtration rate (eGFR and albuminuria, according to the classification of Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (KDIGO from 2013 Materials and Methods: The study was epidemiological, transversal, non interventional type, with 600 subjects unselected patients divided into three subgroups: 200 patients with T1DM, 200 patients with T2DM and 200 age matched subjects without DM. The recorded data have been analyzed using the Statistic Package for Social Sciences (SPSS, the 17.00 software (IBM Corporation, Armonk, NY, United States of America. Results:. We found a statistically significant difference among the three study groups (p < 0.0001 regarding the prognosis of CKD. Conclusions: DM represents an important risk factor for the appearance of CKD but also a negative prognosis factor for the patients with CKD.

  13. Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy

    Science.gov (United States)

    Srivastava, Anand; Adams-Huet, Beverley; Vega, Gloria L; Toto, Robert D

    2016-01-01

    Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo −24.6%, los −38.2%, spiro −51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (−20.9% vs +34.3%, pdyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. Trial registration number NCT00381134; Results. PMID:27388615

  14. Clinical assessment and management of dyslipidemia in patients with chronic kidney disease.

    Science.gov (United States)

    Nitta, Kosaku

    2012-08-01

    Chronic kidney disease (CKD) is a common cause of cardiovascular disease (CVD). Several factors contribute to the onset and progression of atherosclerosis and CVD in CKD patients. Most of the cases of coronary heart disease in the general population can be explained by traditional risk factors, whereas non-traditional risk factors, including oxidative stress, anemia, inflammation, malnutrition, vascular calcification, and endothelial dysfunction, have been proposed to play a central role in the pathogenesis of CVD in CKD patients. However, the precise mechanism of CVD initiation in CKD patients remains unclear. Lipid-lowering therapies may decrease proteinuria, and increase or maintain renal function. Because the serum levels of triglyceride-rich lipoproteins are increased in CKD patients, particularly in advanced stages, the serum non-HDL cholesterol level may be a better biomarker of dyslipidemia than the serum LDL cholesterol level in this population. A meta-analysis showed that statin therapy was associated with decreased albuminuria in comparison with a placebo. Moreover, lipid-lowering therapy with statins is effective in reducing the risk of CVD in the early stages of CKD, whereas the benefit of statins in patients with end-stage renal disease may be limited.

  15. Comparing the Levels of Trace Elements in Patients With Diabetic Nephropathy and Healthy Individuals

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    Makhlough

    2015-06-01

    Full Text Available Background Diabetic nephropathy is the most common cause of end stage renal disease (ESRD in developed countries. Several trace elements were reported to be changed in diabetic nephropathy. Objectives The aim of this study was to investigate changes in serum levels of zinc, copper and chromium and their association with the incidence of ESRD in patients with diabetes. Patients and Methods This study was performed on 70 patients with type 2 diabetic nephropathy (macro and micro-albuminuria and 70 healthy individuals. Samples were collected to survey metals by atomic absorption spectrophotometer. Data was analyzed by SPSS18 using descriptive and inferential analysis methods. Results Mean ± SD levels of Zn, Cu and Cr were significantly decreased in blood samples of patients compared to healthy subjects (P < 0.01. Also the mean concentrations of Cu, Zn and Cr in drinking water of Sari were lower than the accepted limit. Only in one case, Cu was higher than the accepted limit, which was the possibility of contamination by water supply pipes. Conclusions Cu, Zn and Cr play a specific role in the pathophysiology of diabetic nephropathy. Meanwhile in these patients, low serum levels of Cu, Zn and Cr were not associated with factors such as drinking water. Possible causes should be sought in other factors like urine, intervention factors in absorption and utilization and individual conditions.

  16. Risks of rapid decline renal function in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Yi-Jing; Sheen; Wayne; HH; Sheu

    2014-01-01

    Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general,it is defined by the decrease of estimated glomerular filtration rate(e GFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained declinein e GFR of > 5 m L/min per 1.73 m2 per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection.

  17. Epidemiology investigation and associated factors analysis of chronic kidney disease among adults older than 35 years in Tianshan district of Urumqi, Xinjiang%乌鲁木齐市天山区35岁以上成人慢性肾脏病流行病学调查及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    赵红娟; 徐钢; 刘晓城; 陆晨; 岳华; 姬佳妮; 马慧霞; 范淑英; 沙力汗.沙塔尔; 刘伟莉; 朱开春

    2010-01-01

    Objective To investigate the prevalence of chronic kidney disease (CKD)and risk factors in the adult population of Tianshan district in Urumqi, Xinjiang. Methods A total of 2131 residents from 4 communities in Tianshan district of Urumqi city were randomly selected using a stratified, multistage sampling. All the residents were interviewed and tested for morning spot urine of albumin to creatinine ratio (ACR) (abnormal ≥ 30 mg/g), morning spot urine dipstick of hematuria ( abnormal >3 red blood cells/HP or greater) and pyuria ( abnormal> 5 white blood cells/HP) confirmed by microscopy. Renal function was determined with abbreviated MDRD equation [reduced estimated glomerular filtration rate (eGFR)<60 ml ·min-1 ·(1.73 m2)-1]. The associations of kidney damage indicators with age, gender, hypertension, diabetes mellitus, income,education, cholesterol, triglyceride and smoking were examined. Results Eligible data of 2131 subjects were collected in the study. After the adjustment of age and gender component, the prevalence of albuminuria was found in 2.63% (95%CI:1.78%-3.48%) of subjects, hematuria in 7.43%(95%CI:6.11%-8.75%) and reduced renal function in 1.72%(95%CI:1.08%-2.35%).Approximately 9.99%(95%CI:8.47%-11.55%) of subjects had at least one indicator of kidney damage. Multivariate logistic regression revealed that albuminuria, hematuria, age and hyperuricemia were independently associated with reduced renal function. Hematuria and reduced renal function were independently associated with albuminuria. Albuminuria, reduced renal function and female were independently associated with hematuria. Conclusion In urban adult population over 35 years old of Urumqi, a big city in western China, the prevalence of CKD is 9.99%, the recognition is 2.44% and the risk factors of CKD are similar to those of other domestic big cities and western developed countries.%目的 了解乌鲁木齐市天山区35岁以上成人慢性肾脏

  18. MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy.

    Science.gov (United States)

    Qiao, Yingjin; Berg, Anna-Lena; Wang, Pei; Ge, Yan; Quan, Songxia; Zhou, Sijie; Wang, Hai; Liu, Zhangsuo; Gong, Rujun

    2016-01-01

    Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms. PMID:27270328

  19. Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

    Science.gov (United States)

    Liu, Chungang; Song, Jingjing; Teng, Meiyu; Zheng, Xiaoyi; Li, Xiangmei; Tian, Yue; Pan, Minlian; Li, Yuhuan; Lee, Robert J; Wang, Di

    2016-01-01

    Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet-streptozotocin- (STZ-) induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-β-d-glucosaminidase verified CM's renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3β in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats. PMID:27274781

  20. [Importance of laboratory findings in differentiating cranio-cerebral injuries of mild and moderate severity].

    Science.gov (United States)

    Burgman, G P; Iurishchev, E P; Vial'tseva, I N; Ovsiannikova, R P; Smirnova, I V

    1982-01-01

    The authors discuss the results of clinical and laboratory examination of 191 patients among whom 93 had a mild and 98 a moderately severe cranio-cerebral injury. The dynamics of changes in the cerebrospinal fluid, including the changes in its cell composition, and the changes in the morphological compositions of blood during the post-traumatic period were studied. Different aspects of metabolism characterizing the functional condition of the liver, kidneys and adrenals were studied. The condition of blood coagulation was determined with due account for its rheological properties. The results of the statistical analysis of the material obtained show that in judging the depth of the pathophysiological disturbances and differentiating the mild and moderated degrees of cranio-cerebral injury severity it is advisable to use such laboratory tests as those for disorders of the composition of the cerebrospinal fluid (erythrochromia, hyperproteinochromia, pleocytosis, cytological values) and blood (leukocytosis with a shift of the neutrophils to the left, increased Krebs' index, increased ESR), tests for disorders of carbohydrate and protein metabolism (fructosuria, dysproteinemia), for the degree of intensified blood coagulation activity and tests for abnormalities in the renal function (albuminuria, microhematuria).

  1. Podocyte EphB4 signaling helps recovery from glomerular injury.

    Science.gov (United States)

    Wnuk, Monika; Hlushchuk, Ruslan; Janot, Mathilde; Tuffin, Gérald; Martiny-Baron, Georg; Holzer, Philipp; Imbach-Weese, Patricia; Djonov, Valentin; Huynh-Do, Uyen

    2012-06-01

    Eph receptor tyrosine kinases and their ligands (ephrins) have a pivotal role in the homeostasis of many adult organs and are widely expressed in the kidney. Glomerular diseases beginning with mesangiolysis can recover, with podocytes having a critical role in this healing process. We studied here the role of Eph signaling in glomerular disease recovery following mesangiolytic Thy1.1 nephritis in rats. EphB4 and ephrinBs were expressed in healthy glomerular podocytes and were upregulated during Thy1.1 nephritis, with EphB4 strongly phosphorylated around day 9. Treatment with NPV-BHG712, an inhibitor of EphB4 phosphorylation, did not cause glomerular changes in control animals. Nephritic animals treated with vehicle did not have morphological evidence of podocyte injury or loss; however, application of this inhibitor to nephritic rats induced glomerular microaneurysms, podocyte damage, and loss. Prolonged NPV-BHG712 treatment resulted in increased albuminuria and dysregulated mesangial recovery. Additionally, NPV-BHG712 inhibited capillary repair by intussusceptive angiogenesis (an alternative to sprouting angiogenesis), indicating a previously unrecognized role of podocytes in regulating intussusceptive vessel splitting. Thus, our results identify EphB4 signaling as a pathway allowing podocytes to survive transient capillary collapse during glomerular disease.

  2. Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes

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    Thomas Bernd Dschietzig

    2015-03-01

    Full Text Available Background/Aims: In diabetic nephropathy (DN, the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC, there is no specific remedy available. Relaxin-2 (Rlx - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 µg/kg/day and high-dose (320 µg/kg/day Rlx were tested against vehicle (n = 20 each and non-diabetic controls (n = 14 for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-β pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-β-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.

  3. Pathogenesis and Novel Treatment from the Mouse Model of Type 2 Diabetic Nephropathy

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    Masako Furukawa

    2013-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage kidney disease worldwide. However, current treatments remain suboptimal. Many factors, such as genetic and nongenetic promoters, hypertension, hyperglycemia, the accumulation of advanced glycation end products (AGEs, dyslipidemia, and albuminuria/proteinuria itself, influence the progression of this disease. It is important to determine the molecular mechanisms and treatment of this disease. The development of diabetes results in the formation of AGEs, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS within the kidney, which promotes progressive inflammation and fibrosis, leading to DN and declining renal function. A number of novel therapies have also been tested in the experimental diabetic model, including exercise, inhibitors of the RAAS (angiotensin type 1 receptor blockers (ARB, angiotensin-converting enzyme (ACE inhibitors, inhibitors of AGE (pyridoxamine, peroxisome proliferator-activated receptor (PPAR γ agonists (pioglitazone, inhibitors of lipid accumulation (statins and eicosapentaenoic acid (EPA, and the vitamin D analogues. This review summarizes the advances in knowledge gained from our studies and therapeutic interventions that may prevent this disease.

  4. Association between serum cystatin C levels and cardiovascular disease in type 2 diabetic patients.

    Science.gov (United States)

    Triki, Sonia; Fekih, Ons; Hellara, Ilhem; Neffati, Fadoua; Douki, Wahiba; Hamda, Khaldoun Ben; Maatouk, Faouzi; Najjar, Mohamed Fadhel

    2013-01-01

    Serum cystatin C concentration was recently reported as a marker of cardiovascular disease (CVD). In the present study, we evaluated the association between the increase of serum cystatin C levels and the risk of CVD in type 2 diabetes. 42 patients with type 2 diabetes were included in the present study; 27 of them have CVD. The control group consisted of 30 healthy adults. Cystatin C, creatinine, microalbuminuria and CRP were measured on Cobas 6000(TM). Cystatine C level was significantly higher in patients with CVD. A significant difference in serum cystatin C was found in patients with and without CVD among albuminuria. No difference in serum cystatin C levels was found according to number of affected vessels. A cystatin C level above 1.10 mg/L was associated with increase of risk of CVD with significant difference (OR = 42.52; IC 95% 1.455 to 1242.827 and p = 0.029). Our results suggested that the increase of serum cystatin C concentrations is a potential marker for CVD in diabetes. PMID:23906571

  5. [Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?].

    Science.gov (United States)

    Dhia, Rym Ben; Hellara, Ilhem; Harzallah, Olfa; Neffati, Fadoua; Khochtali, Ines; Mahjoub, Sylvia; Najjar, Mohamed Fadhel

    2012-01-01

    Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients. PMID:22565176

  6. Correlates of Osteoprotegerin and Association with Aortic Pulse Wave Velocity in Patients with Chronic Kidney Disease

    Science.gov (United States)

    Leonard, Mary B.; Townsend, Raymond R.; Appel, Lawrence; Wolf, Myles; Budoff, Matt J.; Chen, Jing; Lustigova, Eva; Gadegbeku, Crystal A.; Glenn, Melanie; Hanish, Asaf; Raj, Dominic; Rosas, Sylvia E.; Seliger, Stephen L.; Weir, Matthew R.; Parekh, Rulan S.

    2011-01-01

    Summary Background and objectives Osteoprotegerin (OPG), a cytokine that regulates bone resorption, has been implicated in the process of vascular calcification and stiffness. Design, setting, participants, & measurements Serum OPG was measured in 351 participants with chronic kidney disease (CKD) from one site of the Chronic Renal Insufficiency Cohort Study. Cortical bone mineral content (BMC) was measured by quantitative computed tomography in the tibia. Multivariable linear regression was used to test the association between serum OPG and traditional cardiovascular risk factors, measures of abnormal bone and mineral metabolism, and pulse wave velocity. Results Higher serum OPG levels were associated with older age, female gender, greater systolic BP, lower estimated GFR, and lower serum albumin. OPG was not associated with measures of abnormal bone or mineral metabolism including serum phosphorus, albumin-corrected serum calcium, intact parathyroid hormone, bone-specific alkaline phosphatase, or cortical BMC. Among 226 participants with concurrent aortic pulse wave velocity measurements, increasing tertiles of serum OPG were associated with higher aortic pulse wave velocity after adjustment for demographics, traditional vascular risk factors, and nontraditional risk factors such as estimated GFR, albuminuria, serum phosphate, corrected serum calcium, presence of secondary hyperparathyroidism, serum albumin, and C-reactive protein or after additional adjustment for cortical BMC in a subset (n = 161). Conclusions These data support a strong relationship between serum OPG and arterial stiffness independent of many potential confounders including traditional cardiovascular risk factors, abnormal bone and mineral metabolism, and inflammation. PMID:21940840

  7. Continuous versus intermittent exercise effects on urinary excretion of albumin and total protein.

    Science.gov (United States)

    Montelpare, W J; Klentrou, P; Thoden, J

    2002-09-01

    Several studies have reported post-exercise increases of urinary concentrations of plasma proteins. However, under normal conditions, through mechanisms of size and electrical charge selection, the kidney restricts the clearance of molecules as large as albumin. Post-exercise increases in albuminuria occur following the physiological stress of intense exercise, most likely as a result of the exercise induced blood acidity changes which lead to a change in the arrangement of the albumin molecule, and subsequently the filtration characteristics of the glomerular capillary wall. The purpose of the present study was therefore to determine the extent to which different types of exercise could induce a transient condition of post-exercise increases in the urinary output of total protein and albumin. All 14 males, who agreed to participate in the study, performed a continuous and an intermittent cycling protocol on a stationary bicycle ergometer. The results showed that: a) intermittent exercise had a greater influence than continuous exercise on the total output of urine albumin, and of urine total protein; b) concentrations of blood pH and blood lactate, were associated with changes in the clearance of urine albumin and urine total protein. Post-exercise proteinuria response seems to be transient and therefore renal trauma is not suspected at the early stages of observation. Furthermore, these results indicate that the kidney undergoes distinct physiological adjustments during exercise, and that these adjustments are relative to the intensity of the exercise stress. PMID:12413038

  8. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    Md. Abdul Hye Khan

    2014-09-01

    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  9. A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways.

    Science.gov (United States)

    Ka, Shuk-Man; Kuoping Chao, Louis; Lin, Jung-Chen; Chen, Shui-Tein; Li, Wen-Tai; Lin, Chien-Nan; Cheng, Jen-Che; Jheng, Huei-Ling; Chen, Ann; Hua, Kuo-Feng

    2016-02-01

    Uncontrolled inflammation is a leading cause of various chronic diseases. Cinnamaldehyde (CA) is a major bioactive compound isolated from the essential oil of the leaves of Cinnamomum osmophloeum kaneh that exhibits anti-inflammatory activity; however, the use of CA is limited by its cytotoxicity. Here, we synthesized three CA derivatives and identified 4-hydroxycinnamaldehyde-galactosamine (HCAG) as a low toxicity anti-inflammatory compound in vitro (HCAG IC50 ≫ 1600 µM; CA IC50=40 µM) and in vivo. HCAG reduced pro-inflammatory mediator expression in LPS-activated macrophages by inhibiting MAPK and PKC-α/δ phosphorylation, decreasing ROS generation and reducing NF-κB activation. HCAG also reduced NLRP3 inflammasome-derived IL-1β secretion by inhibiting the ATP-mediated phosphorylation of AKT and PKC-α/δ. In a mouse model of LPS-induced renal inflammation, we observed reduced albuminuria and a mild degree of glomerular proliferation, glomerular sclerosis and periglomerular inflammation in the HCAG-treated mice compared with the vehicle-treated mice. The underlying mechanisms for these renoprotective effects involved: (1) inhibited NLRP3 inflammasome activation; (2) decreased superoxide anion levels and apoptosis; and (3) suppressed activation of NF-κB and related downstream inflammatory mediators. PMID:26675345

  10. To compare anti-albumin urea effects of valsartan alone with combination of valsartan and amlodipine in patients of chronic kidney disease

    Science.gov (United States)

    Ameen; Kashif, Muhammad Ali; Sumreen

    2016-01-01

    Objective: To compare anti-albumin urea effects of Valsartan alone with combination of Valsartan and Amlodipine in patients of chronic kidney disease. Methods: This randomized clinical trial was conducted at the Department of Medicine, Combined Military Hospital Bahawalpur, from April 2014 to 30 September 2014. 140 patients of chronic kidney disease with baseline blood pressure more than 140/90mm Hg having raised urinary albumin: creatinine ratio (UACR). UACR more than 3.5 mg/mmol was considered abnormal. Group-A was treated with Valsartan 80mg daily and Group-B was treated with valsartan 80 and amlodipine 10mg once a day. We did not change the dose of drugs and check spot UACR at base line and after six months with therapy and compare improvement in UACR between Group-A and B. Data was analyzed by statistical software packages (SPSS 16.0). Results: In both the groups, BP was significantly lower than the respective value. Mean decrease in spot UACR in Group-A was 3.18±2.64 mg/mmol and UACR in Group-B mean decrease in UACR was 13.01±20.11 mg/mmol. P value was< 0.05. Conclusion: The combination therapy of valsartan with amlodipine significantly lowers the albuminuria in chronic Kidney disease and reduce the progression of disease as compared to Valsartan alone therapy. PMID:27375700

  11. Urinary Analysis of Fluid Retention in the General Population: A Cross-Sectional Study

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    Grankvist, Nina; Krizhanovskii, Camilla

    2016-01-01

    Objective Renal conservation (retention) of fluid might affect the outcome of hospital care and can be indicated by increased urinary concentrations of metabolic waste products. We obtained a reference material for further studies by exploring the prevalence of fluid retention in a healthy population. Methods Spot urine sampling was performed in 300 healthy hospital workers. A previously validated algorithm summarized the urine-specific gravity, osmolality, creatinine, and color to a fluid retention index (FRI), where 4.0 is the cut-off for fluid retention consistent with dehydration. In 50 of the volunteers, we also studied the relationships between FRI, plasma osmolality, and water-retaining hormones. Results The cut-off for fluid retention (FRI ≥ 4.0) was reached by 38% of the population. No correlation was found between the FRI and the time of the day of urine sample collection, and the FRI was only marginally correlated with the time period spent without fluid intake. Volunteers with fluid retention were younger, generally men, and more often had albuminuria (88% vs. 34%, P dehydration is common in healthy staff working in a Swedish hospital. PMID:27764121

  12. Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase.

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    Peng, Chiung-Huei; Yang, Yi-Sun; Chan, Kuei-Chuan; Wang, Chau-Jong; Chen, Mu-Lin; Huang, Chien-Ning

    2014-10-01

    The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy. PMID:25226384

  13. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

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    Viazzi, Francesca; Bonino, Barbara; Cappadona, Francesca; Pontremoli, Roberto

    2016-08-01

    The Renin-Angiotensin-Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition.

  14. Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients.

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    Fiseha, Temesgen

    2015-01-01

    Diabetic nephropathy (DN) is a serious complication of diabetes associated with increased risk of mortality, and cardiovascular and renal outcomes. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney function and improve patient outcomes. Urinary biomarkers may be elevated in diabetic patients even before the appearance of microalbuminuria, and can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early DN). We reviewed some new and important urinary biomarkers, such as: Neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase (NAG), Cystatin C, alpha 1-microglobulin, immunoglobulin G or M, type IV collagen, nephrin, angiotensinogen and liver-type fatty acid-binding protein (L-FABP) associated with early DN in type 2 diabetic patients. Our search identified a total of 42 studies that have been published to date. Urinary levels of these biomarkers were elevated in type 2 diabetic patients compared with non-diabetic controls, including in patients who had no signs indicating nephropathy (without microalbuminuria), and showed positive correlation with albuminuria. Despite the promise of these new urinary biomarkers, further large, multicenter prospective studies are still needed to confirm their clinical utility as a screening tool for early type 2 DN in every day practice. PMID:26146561

  15. Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

    Science.gov (United States)

    Ellis, Robert J; Small, David M; Vesey, David A; Johnson, David W; Francis, Ross; Vitetta, Luis; Gobe, Glenda C; Morais, Christudas

    2016-03-01

    In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.

  16. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

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    Abraham Said Arellano-Buendía

    2014-01-01

    Full Text Available Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg. Oxidative stress was assessed by measuring the activity of catalase (CAT, glutathione peroxidase (GPx, and superoxide dismutase (SOD; additionally, expression levels of 3-nitrotyrosine (3-NT, 4-hydroxynonenal (4-HNE, and oxidized protein (OP were quantified. Whole glomerular filtration rate (GFR was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL, osteopontin (uOPN, and N-acetyl-β-D-glucosaminidase (uNAG was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.

  17. YKL-40 - an emerging biomarker in cardiovascular disease and diabetes

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    Rathcke Camilla

    2009-01-01

    Full Text Available Abstract Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis. Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial dysfunction, atherosclerosis, cardiovascular disease and diabetes and look ahead on future perspectives of YKL-40 research.

  18. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

    Science.gov (United States)

    Arellano-Buendía, Abraham Said; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia-Rodríguez, Edilia; Sánchez-Lozada, Laura Gabriela; Osorio-Alonso, Horacio

    2014-01-01

    Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes. PMID:25243053

  19. LONG-TERM THERAPY WITH INDAPAMIDE IN ELDERLY AND SENILE PATIENTS WITH HYPERTENSION: CARDIORENOPROTECTIVE EFFECTS AND INFLUENCE ON QUALITY OF LIFE

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Aim. To estimate cardiorenoprotective effect of 12-month therapy by indapamide in elderly and senile patients with arterial hypertension (HT and its influence on quality of life.Material and methods. 40 elderly and senile patients with HT were examined. 70% of patients received monotherapy by indapamide 2,5 mg once daily and 30% of patients were treated with indapamide and lisinopril combination. Duration of observation was 12 months. Ambulatory blood pressure (BP monitoring, echocardiography, plasma lipid profile, glycemia and uricemia levels and potassium serum level was evaluated initially and after 12 months of therapy. Glomerular filtration rate and albuminuria as well as patient quality of life also was evaluated.Results. Target BP level was reached in all patients during 12 month therapy. Reduction of average 24-hour, day and night BP, BP load, rate of morning BP rising was observed. Negative influence on BP variability was not found. Improvement of daily BP profile also was found. The indapamide reduced left ventricle mass, improved renal function, vessel resistance and quality of life. Negative influence of long-term therapy with indapamide on lipid, glucose, purine metabolism and serum potassium level was not observed.Conclusion. Indapamide is an effective antihypertensive drug for long-term treatment of elderly and senile patients with HT of 1-2 degree.

  20. Copper and zinc metabolism in aminonucleoside-induced nephrotic syndrome.

    Science.gov (United States)

    Pedraza-Chaverrí, J; Torres-Rodríguez, G A; Cruz, C; Mainero, A; Tapia, E; Ibarra-Rubio, M E; Silencio, J L

    1994-01-01

    Copper (Cu) and zinc (Zn) were measured in urine, serum and tissues from rats with nephrotic syndrome (NS) induced with a single subcutaneous dose of puromycin aminonucleoside (PAN; 15 mg/100 g BW). Control animals were pair-fed. Urine was collected daily, and the rats were sacrificed on day 10. PAN-nephrotic rats had proteinuria (days 3-10), high urinary Cu (days 1, 2, 4-10) and Zn (days 3-10) excretion. On day 10, nephrotic rats had: (a) albuminuria, hypoalbuminemia, hypoproteinemia, high urine and low serum levels of ceruloplasmin; (b) low Cu and Zn serum levels; (c) high clearance and fractional excretion of Cu and Zn, and (d) low kidney and liver Cu content and essentially normal tissue Zn levels. The alterations in Cu metabolism were more intense than those in Zn metabolism. Urine Cu and Zn showed a positive correlation with urine total protein on days 3-10 which suggests that high urinary excretion of Cu and Zn may be due to the excretion of its carrier proteins. In conclusion, these rats did not show a typical Zn deficiency but a clear decrease in Cu in the liver and kidney.

  1. Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress.

    Science.gov (United States)

    Zheng, Jing; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; McCarty, Mark F; Fujii, Masakazu; Ikeda, Noriko; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-01-15

    We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy. PMID:23115122

  2. Overexpression of Mafb in podocytes protects against diabetic nephropathy.

    Science.gov (United States)

    Morito, Naoki; Yoh, Keigyou; Ojima, Masami; Okamura, Midori; Nakamura, Megumi; Hamada, Michito; Shimohata, Homare; Moriguchi, Takashi; Yamagata, Kunihiro; Takahashi, Satoru

    2014-11-01

    We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target.

  3. Intravenous injection of ioxilan, iohexol and diatrizoate

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    Thomsen, H.S.; Dorph, S.; Mygind, T.; Sovak, M.; Nielsen, H.; Rygaard, H.; Larsen, S.; Skaarup, P.; Hemmingsen, L.; Holm, J.

    Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.

  4. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury.

    Science.gov (United States)

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D

    2014-01-01

    Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  5. Adriamycin nephrosis and contrast media; A comparison between diatrizoate and iohexol in rats

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    Thomsen, H.S.; Golman, K.; Hemmingsen, L.; Larsen, S.; Skaarup, P. (Koebenhavns Amts Sygehus, Herlev (Denmark). Dept. of Diagnostic Radiology Koebenhavns Amts Sygehus, Herlev (Denmark). Dept. of Nuclear Medicine Koebenhavns Amts Sygehus, Herlev (Denmark). Inst. of Pathology Centralsygehuset, Nykoebing Falster (Denmark). Dept. of Clinical Chemistry Malmoe Allmaenna Sjukhus (Sweden). Dept. of Experimental Research)

    1990-01-01

    Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 9 days after intravenous injection of either diatrizoate, iohexol, or saline in 27 Wistar rats with nephrosis induced by Adriamycin 42 days before. Another 9 rats exposed to neither Adriamycin nor contrast media served as controls. None of the contrast media caused further increased albuminuria of significance, whereas both induced significantly increased excretion of all 5 tubular components. The excretion of NAG and sodium was significantly higher following diatrizoate than following iohexol. From 24 h post injection there was no significantly greater excretion of any of the components after either diatrizoate or iohexol than after saline among the rats given Adriamycin. At the end of day 9 after contrast medium injection neither serum sodium, potassium, glucose, urea, creatinine, nor albumin revealed any contrast media related changes. Kidney histology showed quantitatively larger lesions in kidneys exposed to Adriamycin and contrast media than in kidneys exposed to Adriamycin and saline. There were no differences between the two contrast media groups. It is thus concluded, that both high osmolar ionic and low osmolar non-ionic contrast media cause temporary tubular dysfunction but no further glomerular dysfunction in rats with nephrosis induced by Adriamycin. The histologic findings indicate that both media may worsen non-reversible renal lesions. (orig.).

  6. Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes.

    Science.gov (United States)

    Coughlan, Melinda T; Nguyen, Tuong-Vi; Penfold, Sally A; Higgins, Gavin C; Thallas-Bonke, Vicki; Tan, Sih Min; Van Bergen, Nicole J; Sourris, Karly C; Harcourt, Brooke E; Thorburn, David R; Trounce, Ian A; Cooper, Mark E; Forbes, Josephine M

    2016-05-01

    Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD.

  7. Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice.

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    Abed, Ahmed; Toubas, Julie; Kavvadas, Panagiotis; Authier, Florence; Cathelin, Dominique; Alfieri, Carlo; Boffa, Jean-Jacques; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E

    2014-10-01

    Excessive recruitment of monocytes and progression of fibrosis are hallmarks of chronic kidney disease (CKD). Recently we reported that the expression of connexin 43 (Cx43) was upregulated in the kidney during experimental nephropathy. To investigate the role of Cx43 in the progression of CKD, we interbred RenTg mice, a genetic model of hypertension-induced CKD, with Cx43+/- mice. The renal cortex of 5-month-old RenTgCx43+/- mice showed a marked decrease of cell adhesion markers leading to reduced monocyte infiltration and interstitial renal fibrosis compared with their littermates. In addition, functional and histological parameters such as albuminuria and glomerulosclerosis were ameliorated in RenTgCx43+/- mice. Interestingly, treatment with Cx43 antisense produced remarkable improvement of renal function and structure in 1-year-old RenTg mice. Similar results were found in Cx43+/- or wild-type mice treated with Cx43 antisense after obstructive nephropathy. Furthermore, in these mice, Cx43 antisense attenuated E-cadherin downregulation and phosphorylation of the transcription factor Sp1 by the ERK pathway resulting in decreased transcription of type I collagen gene. Interestingly, Cx43-specific blocking peptide inhibited monocyte adhesion in activated endothelium and profibrotic pathways in tubular cells. Cx43 was highly increased in biopsies of patients with CKD. Thus, Cx43 may represent a new therapeutic target against the progression of CKD.

  8. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.

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    Paola Krall

    Full Text Available Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6 gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.

  9. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  10. P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cassia T; Fernandes, Maria Jose S; Paredes-Gamero, Edgar J; Buri, Marcus V; Curi, Marcus V; Ferreira, Alice T; Araujo, Sergio R R; Punaro, Giovana R; Maciel, Fabiane R; Nogueira, Guilherme B; Higa, Elisa M S

    2014-01-01

    Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all prats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy. PMID:24940871

  11. Relationship of endothelial dysfunction with degree of renal function damage and lipidemic profile in patients with type 2 diabetes mellitus and hypertension

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    Pertseva N.O.

    2014-09-01

    Full Text Available In the article defining relationship between endothelial dysfunction, the degree of renal and lipidemic profile damage in 234 patients with type 2 diabetes mellitus with hypertension was carried depending on the quality of glycemic control. It is shown that the deepening of endothelial dysfunction in patients with insufficient and poor compensation tightly correlates with the degree of renal and lipidemic disorders. In these patients there was a significant increase in the level of albuminuria, reduction in glomerular filtration rate, increase of concentrations of urea and creatinine. Against the background of poor hyperglycemia, compensation total cholesterol, low density lipoprotein content increases by 73,3% (p<0.05, hype¬rtriglyceridemia twice exceeds the control values. In patients with type 2 diabetes mellitus with poor compensation the most significant correlation links were observed between the concentration of endothelin-1 and the level of microalbuminuria (r=+0,79, as well as the content of low density lipoprotein cholesterol (r=+0.81. Thrombomodulin concentration is in direct correlation with microalbuminuria (r=+0.76, hypercholesterolemia (r=+0.80 and hypertriglyceridemia (r=+0.83, indicating to increasing interaction between the pathogenetic mechanisms which cause depression of endothelial dysfunction, renal and dyslipidemic disorders with increasing hyperglycemia.

  12. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

    Science.gov (United States)

    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.

  13. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

    Science.gov (United States)

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-01-01

    Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

  14. A randomized trial of dietary sodium restriction in CKD.

    Science.gov (United States)

    McMahon, Emma J; Bauer, Judith D; Hawley, Carmel M; Isbel, Nicole M; Stowasser, Michael; Johnson, David W; Campbell, Katrina L

    2013-12-01

    There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.

  15. Phagocytosis by glomerular endothelial cells in infection-related glomerulopathy.

    Science.gov (United States)

    van Velthuysen, M L; Mayen, A E; Prins, F A; de Heer, E; Bruijn, J A; Fleuren, G J

    1994-01-01

    Glomerulonephritis in BALB/c mice following infection with Trypanosoma brucei is characterized by albuminuria and glomerular deposition of immunoglobulins. Electron-dense deposits are present in the mesangium, as well as subendothelially and subepithelially along the glomerular capillary wall. In this study the nature of intracytoplasmic, electron-dense, round structures observed in glomerular endothelial cells was investigated by immunoelectron-microscopy and enzyme histochemistry. The presence of these structures was related in time with the development of proteinuria. Mice from the C57BL10 strain, which upon infection develop glomerular immune complexes without proteinuria, were examined as well. The results demonstrated that the first endothelial changes, occurring 3-4 weeks after infection, were swelling of endothelial cells containing intracytoplasmic, electron-dense, round structures. These changes were seen prior to the onset of proteinuria, and were not present in glomeruli of mice that did not develop proteinuria. The endothelial granules were shown to contain immunoglobulins and typical lysosomal enzymes, providing evidence for phagocytosis by the glomerular endothelial cells. Liver endothelial cells did not show comparable changes. Thus, local phagocytosis by glomerular endothelial cells is shown to be a specific event in the development of glomerular disease. PMID:7800204

  16. JAK inhibition in the treatment of diabetic kidney disease.

    Science.gov (United States)

    Brosius, Frank C; Tuttle, Katherine R; Kretzler, Matthias

    2016-08-01

    Diabetic kidney disease (DKD) is the most common cause of kidney failure in many countries today, but treatments have not improved in the last 20 years. Recently, systems biology methods have allowed the elucidation of signalling pathways and networks involved in the progression of DKD that were not well appreciated previously. A prominent pathway found to be integrally associated with DKD progression is the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Increased expression of JAK-STAT genes was found in multiple cells in the kidney, including glomerular podocytes, in both early and progressive DKD. Subsequent experiments in a mouse diabetic model showed that enhanced expression of JAK2 selectively in glomerular podocytes increased functional and pathological features of DKD. Finally, a yet unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled study of the efficacy of a selective JAK1 and JAK2 inhibitor has been conducted in type 2 diabetic participants with DKD. In this trial there was a reduction of albuminuria in participants who received the active inhibitor compared with those who received a placebo These results support the further study of JAK inhibitors as a new therapy for DKD. This review summarises a presentation given at the 'Anti-inflammatory interventions in diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by an overview by the Session Chair, Hiddo Heerspink (DOI: 10.1007/s00125-016-4030-4 ). PMID:27333885

  17. Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes.

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    Pamela Maher

    Full Text Available The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE, serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.

  18. Treatment and Prevention of Common Complications of Chronic Kidney Disease

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    Sheikh Salahuddin Ahmed

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a worldwide public health problem with an increasing incidence and prevalence. Outcomes of CKD include not only complications of decreased kidney function and cardiovascular disease but also kidney failure causing increased morbidity and mortality. Unfortunately, CKD is often undetected and undertreated because of its insidious onset, variable progression, and length of time to overt kidney failure. Diabetes is now the leading cause of CKD requiring renal replacement therapy in many parts of the world, and its prevalence is increasing disproportionately in the developing countries. This review article outlines the current recommendations from various clinical guidelines and research studies for treatment, prevention and delaying the progression of both CKD and its common complications such as hypertension, anemia, renal osteodystrophy, electrolyte and acid-base imbalance, and hyperlipidemia. Recommendations for nutrition in CKD and measures adopted for early diabetic kidney disease to prevent further progression have also been reviewed. There is strong evidence that early detection and management of CKD can prevent or reduce disease progression, decrease complications and improve outcomes. Evidence supports that achieving optimal glucose control, blood pressure, reduction in albuminuria with a multifactorial intervention slows the progression of CKD. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria, a factor important for the progression of CKD.

  19. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.

    Science.gov (United States)

    Inzucchi, Silvio E; Zinman, Bernard; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Hantel, Stefan; Espadero, Rosa-Maria; Woerle, Hans-Jürgen; Broedl, Uli C; Johansen, Odd Erik

    2015-03-01

    Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia. In this review, we outline those CV risk factors that this class appears to influence and provide the design features and trial characteristics of six ongoing outcome trials involving more than 41,000 individuals with T2DM. Those risk factors beyond glucose that can potentially be modulated positively with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity, hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels and oxidative stress. On the other hand, small increases in low-density lipoprotein (LDL)-cholesterol levels have also been observed for the class, which theoretically might offset some of these benefits. The potential translational impact of these effects is being tested with outcome trials, also reviewed in this article, powered to assess both macrovascular as well as certain microvascular outcomes in T2DM. These are expected to begin to report in late 2015. PMID:25589482

  20. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

    Energy Technology Data Exchange (ETDEWEB)

    Moscovitch, M.; Rosenmann, E.; Neeman, Z.; Slavin, S.

    1983-02-01

    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.

  1. Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

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    Simon J Freeley

    Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

  2. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria.

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    Ioannis N Petropoulos

    Full Text Available Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS, vibration perception threshold (VPT, peroneal motor nerve conduction velocity (PMNCV, sural sensory nerve conduction velocity (SSNCV and in vivo corneal confocal microscopy (IVCCM], retinopathy (digital fundus photography and albuminuria status [albumin: creatinine ratio (ACR].53 patients with Type 1 diabetes with (n=37 and without retinopathy (n=16 were compared to control subjects (n=27. SSNCV, corneal nerve fibre (CNFD and branch (CNBD density and length (CNFL were reduced significantly (p<0.001 in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001 reduced in diabetic patients without microalbuminuria (n=39, compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.

  3. DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

    Science.gov (United States)

    Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

    2016-05-01

    Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

  4. XbaI GLUT1 Gene Polymorphism and the Risk of Type 2 Diabetes with Nephropathy

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    Ioannis Stefanidis

    2009-01-01

    Full Text Available Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1 contributes to development of microangiopathy in diabetes mellitus type 2 (DM patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN. Study population (n = 240 consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN, and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(− carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR 2.08 [95% confidence interval (1.14–3.79]. However, there was no evidence of association between XbaI(− and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55–2.26. Thus, the GLUT1 XbaI(− allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN.

  5. Increased Oxidative DNA Damage in Placenta Contributes to Cadmium-Induced Preeclamptic Conditions in Rat.

    Science.gov (United States)

    Zhang, Xiaojie; Xu, Zhangye; Lin, Feng; Wang, Fan; Ye, Duyun; Huang, Yinping

    2016-03-01

    To explore the possible mechanisms of cadmium (Cd)-induced preeclamptic conditions in rats. In the present study, we introduced the in vivo model of preeclampsia by giving intraperitoneal injections of cadmium chloride (CdCl2) to pregnant rats from gestational day (GD) 4 to 19. Maternal body weights were recorded on GD 0, 14, and 20, while their systolic blood pressures (SBPs) monitored on GD 3, 11, and 18. On GD 20, rats were sacrificed and the specimens were collected. The morphological changes of placenta and kidney tissues of pregnant rats were examined by hematoxylin and eosin staining assay. Blood Cd level was detected by inductively coupled plasma mass spectrometry. Total antioxidant capacity (TAC) was evaluated using FRAP method and total nitrite (NOx) was detected with Griess reagent. Antioxidative factors and DNA damage/repair biomarkers were measured by real-time qPCR, western blot or immunohistochemistry study. The current results showed that CdCl2-treated pregnant rats developed preeclampsia (PE)-like manifestations, such as hypertension, albuminuria, with decreased TAC and increased blood Cd level, and pro-oxidative/antioxidative or DNA damage/repair biomarkers. Our study demonstrated that increased oxidative DNA damage in placenta could contribute to Cd-induced preeclamptic conditions in rat. PMID:26194818

  6. Time Dependent Relative Risks in Life Insurance Medical Underwriting.

    Science.gov (United States)

    Kneepkens, Robert F

    2015-01-01

    Introduction .- Life insurance medicine focuses on mortality hazards in specified periods. People are free to insure their lives for shorter or longer terms. Because the chosen terms range from 1 year to a life time, life insurers have to take into account the fact that the predictive value of risk indicators can and will change over time. The time a risk indicator keeps its predictive value, will be dependent on its biological effects, volatility, and treatability. For a given applicant this implies that the relative hazard (RH) calculated for his/her medical condition should be dependent on the term of the insurance. The main objective of this study is to determine if some commonly used risk indicators - previously used to study age dependency of relative risks - have a predictive value that increases with the observation period. (1) Methods .- This population-based cohort study uses NHANES-data files from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES Linked Mortality Files 2010. Only participants aged 20 to 69 that were examined in mobile examination centers, without a history of some prevalent high risk diseases were included. The observed mortality was compared to the expected mortality in a Generalized Linear Model (GLM) with Poisson error structure with two reference populations, which both can serve as preferred reference for life insurers: The United States Life Tables 2008 (USLT) and the 2008 Valuation Basic Tables (VBT) based on the insured population of 35 US Life insurers. The time dependency of the RHs of the systolic blood pressure (SBP), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), serum albumin and albuminuria, was assessed, with correction for ethnicity, household income, history of diabetes mellitus, BMI and serum cholesterol. To be able to compare the results with the results of the Age Dependency Study (ADS), the same data, risk indicators, statistical analysis method, and the

  7. Avaliação de diferentes métodos imunoturbidimétricos para determinação de albumina urinária: impacto na classificação dos estágios da nefropatia diabética Evaluation of different immunoturbidimetric methods to measure urinary albumin: impact in the classification of diabetic nephropathy stages

    Directory of Open Access Journals (Sweden)

    Andrea Elisabet Wendland

    2007-12-01

    Full Text Available INTRODUÇÃO: A nefropatia diabética (ND acomete até 40% dos pacientes diabéticos e o diagnóstico precoce pode evitar a evolução para estágios avançados. O rastreamento deve ser realizado pela medida de albumina urinária (AlbU utilizando-se o método quantitativo sensível. OBJETIVO: Avaliar diferentes métodos imunoturbidimétricos de determinação de AlbU para a classificação dos estágios da ND. MATERIAL E MÉTODO: A albumina foi dosada em 167 urinas (65 urinas de 24 h e 102 amostras casuais por dois métodos imunoturbidimétricos: kit Aptec-BioSys, ADVIA® 1650 Bayer (AlbUAdvia e kit MAlb Urin-Pack Bayer®, CobasMira® Roche(AlbUCobas. AlbUCobas foi definido como método comparativo e utilizado para classificar as amostras em normoalbuminúricas (albuminúria 300 mg/24 h ou > 174 mg/l, n = 31. Os coeficientes de variação (CV intra e interensaio, sensibilidade e linearidade dos métodos foram calculados. As concordâncias analítica e diagnóstica foram analisadas por regressão Deming, gráficos de Bland-Altman e por coeficiente kappa. RESULTADOS: Os CVs intra e interensaio foram BACKGROUND: Diabetic nephropathy (DN affects up to 40% of diabetic patients and must be screened by the measurement of urinary albumin with a sensitive quantitative method. OBJECTIVE: To evaluate the impact of different immunoturbidimetric methods to measure albuminuria in the classification of DN stages. MATERIAL AND METHOD: Albumin was measured in 167 urine samples (65 24 h samples and 102 casual samples by two immunoturbidimetric methods: Aptec BioSys, ADVIA® 1650 Bayer (AlbUAdvia and Malb Urin-Pack Bayer®, CobasMira® Roche (AlbUCobas. AlbUCobas was definedas the comparative method used to classify the samples in: normoalbuminuric (albuminuria 300 mg/24 h or > 174 mg/l; n = 31. The intra and interassay coefficients of variation (CVs, sensitivity and linearity of each method were calculated and the analytical and diagnostic agreements were

  8. The significance of detection of D-dimer, fibrinogen and antithrombin-Ⅲin the patients with typy-2 diabet-ic nephropathy%D-二聚体、纤维蛋白原及抗凝血酶Ⅲ联合检测对早期2型糖尿病肾病的诊断价值

    Institute of Scientific and Technical Information of China (English)

    杨玲

    2015-01-01

    目的:探究D-二聚体、纤维蛋白原( FIB)及抗凝血酶Ⅲ( AT-Ⅲ)联合检测2型糖尿病早期肾损伤的临床诊断价值。方法选取某院2型糖尿病患者206例,根据24 h尿白蛋白排泄率( UAE)分为无蛋白尿组116例( UAE<30 mg/24 h)与微量白蛋白尿组90例(30 mg/24 h≤UAE<300 mg/24 h),并选取同期健康体检者103例作为健康对照组,比较血浆D-二聚体、FIB、AT-Ⅲ3项指标的变化。结果微量白蛋白尿组D-二聚体、FIB含量明显高于无蛋白尿组和健康对照组,差异均有统计学意义(P<0畅05),而三组AT-Ⅲ的活性比较差异无统计学意义(P>0畅05)。3项指标联合检测的微量蛋白尿组患者为93畅3%,比单项检测的阳性率高,差异有统计学意义(P<0畅05)。 D-二聚体、FIB、AT-Ⅲ与尿白蛋白排泄率呈正相关,相关系数(r)依次为0畅812、0畅672、0畅621(P<0畅05)。结论 D-二聚体、FIB检测对于2型糖尿病肾病的早期判断以及疾病的早期预防和病情监测有重要意义。%Objective To explore the D-dimer, fibrinogen (FIB), antithrombin Ⅲ (AT-Ⅲ) joint detection of early renal damage in type 2 diabetes to assess the diagnostic value of clinical application.Methods According to the 24 h urine albumin excre-tion rate ( UAE) , 206 patients selected from type 2 diabetes patients were divided into 116 cases without albuminuria group ( UAE0.05).Three indicators of joint detection of trace albuminuria group of patients was 93.3%, positive rate than single detection are high, the difference was statistically significant (P<0.05).D-dimer, FIB, the AT-Ⅲand UAE are positively related to the level of the correlation coefficient r of 0.812, 0.672, and 0.621 (P<0.05).Conclusion The detection of D-dimer, FIB in type 2 diabetic nephropathy early judgement and early prevention of disease and illness monitoring is im-portant.

  9. Association of non-alcoholic fatty liver disease and urinary albumin excretion rate in patients with type 2 dibetes mellitus%2型糖尿病患者非酒精性脂肪肝与尿白蛋白排泄率的关系

    Institute of Scientific and Technical Information of China (English)

    张育仁; 吴静; 李春燕

    2012-01-01

    Objective To investigate the relationship between urinary albumin excretion rate( UAER )and non-alcoholic fatty liver disease( NAFLD )in patients with type 2 dibetes mellitus( T2DM ). Methods Two hundred twenty eight patients were investigated respectively. The patients were divided into two groups( NAFLD group and non-NAFLD group )by liver ultrasonography and disease history, forty heathy persons who were matched for age and sex were served as control, then their clinical data were collected and compared in order to find the differences of biochemical indicators and UAER. Results NAFLD group had higher levels of body mass index( BMI ), triglyceride ( TG),fast insulin and C peptide level, uric acid, homeostasis model assessment HOMA-IR )than those of without NAFLD( P < 0. 05 ). Results of the Chi-square test showed that the mobility of trace albuminuria and mass albuminuria was higher in NAFLD group than that of without NAFLD( x2 = 23. 905, P = 0. 001 ). Logistic analysis showed that BMI( OR = 4. 66 , P = 0. OOf ), TG( OR = 8. 46, P = 0. 000 )and UAER( OR = 3. 73 , P = 0. 003 )were important risk factors for T2DM complicated with NAFLD. Conclusions NAFLD is closely related with higher BMI, TG and UAER in T2DM patients. The mobility of diabetic nephropath)' is significantly higher in T2DM complicated with NAFLD than that of without NAFLD.%目的 探讨合并非酒精性脂肪肝(NAFLD)的2型糖尿病(T2DM)患者尿白蛋白排泄率(UAER)的变化特点及其相关性.方法 T2DM患者228例,根据是否合并NAFLD分为糖尿病合并NAFLD组(135例)和糖尿病无NAFLD组(93例),另选年龄、性别匹配的40例健康受试者为对照组,比较两组患者体重指数(BMI)、空腹血糖(FPG)、血脂、空腹胰岛素(FINS)、空腹C肽、胰岛素抵抗指数(HOMA-IR)、24h UAER的差异,用卡方检验分析两组间正常、微量和大量UAER的分布差异,进一步以T2DM合并NAFLD为应变量,以各临床生化指标为自变量,用单因素和多因

  10. 2型糖尿病患者腹腔内脏脂肪面积与尿白蛋白排泄率相关性分析%Association of visceral adiposity with urinary albumin excretion in type 2 diabetics

    Institute of Scientific and Technical Information of China (English)

    翟莎; 王战建

    2011-01-01

    .51).lg (24 h-UAE) increased 0.26 units as VA expanded 100 cm2, i.e. 0.15 units after relative factor adjusting. After gender and triglyceride adjusting, the odds ratio of heavy albuminuria in group C was 2.75 versus that in group A. And the OR was 3.87 in group D.Conclusion Expansion of VA is a risk factor for an elevated risk of 24 h-UAE. With the expansion of VA, the prevalence of heavy albuminuria increases.

  11. Epidemiologic Investigation of Chronic Kidney Disease in Changchun Adult Male Population%长春市成年男性慢性肾脏病流行病学调查

    Institute of Scientific and Technical Information of China (English)

    李银辉; 佟丹梅; 王晶; 刘水仙; 刘宝玲; 魏宇鹏; 闫利

    2015-01-01

    Objective To investigate the prevalence and risk factors of chronic kidney disease(CKD)in Changchun adult male population . MethodsQuestionnaire(anamnesis, smoking, drink)of risk factors of CKD; Physical Examination (blood pressure, height and body mass);Kidney related testing (uromicroprotein/creatinine ratio; urine and sediment;serum creatinine; and to estimate glomerular ifltration rate). Detection of risk factors including blood sugar, blood uric acid blood lipid. Through statistical analysis , to investigate the prevalence and risk factors of CKD in Changchun adult male population .ResultsEligible data of 3694 subjects were enrolled in the study. The prevalence of albuminuria was 15.29%. reduced of eGFR was 1.32%, hematuria was 4.87%. and CKD was16.24% ,the recognition was 6.17%.Independent risk factors of albuminuria were age, hypertension, high uric acid, high cholesterol and high BMI.Independent risk factors of CKD were age, hypertension, high uric acid, high cholesterol and high BMI.Conclusions The prevalence of CKD is quite high and the recognition rate is low in Changchun adult male population. Risk factors of CKD were age, hypertension, high uric acid, high cholesterol and high BMI.%目的:探讨长春市成年男性人群中慢性肾脏病(CKD)的患病情况和相关危险因素。方法通过对长春市成年男性健康体检,进行CKD及相关危险因素的问卷调查(既往史、吸烟、饮酒等)、体格检查(血压、身高和体重质量)和肾脏相关检测(尿微量白蛋白/肌酐比值;尿常规及沉渣;血清肌酐;并估算肾小球滤过率)。同时还进行危险因素相关检测包括血糖;血尿酸;血脂水平检测。了解长春市成年男性CKD的患病情况及相关危险因素。结果在3694例资料完整的人群中,白蛋白尿的患病率为15.29%,肾功能下降的患病率为1.32%,血尿的患病率为4.87%。该人群中CKD的患病率为16.24%,知晓率为6.17%。多因

  12. 胃旁路术对糖尿病肾病蛋白尿影响的随访研究%Effect of gastric bypass on diabetic nephropathy with microalbuminuria:one year follow-up study

    Institute of Scientific and Technical Information of China (English)

    张弘玮; 狄建忠; 于浩泳; 韩晓东; 张频

    2015-01-01

    目的:探讨胃旁路术对糖尿病肾病(diabetic nephropathy,DN)的疗效。方法:回顾性分析58例接受胃旁路术的肥胖合并DNⅢ/Ⅳ期病人,随访1年分析手术对2型糖尿病、血压、肾功能以及蛋白尿的影响。结果:术后1年降糖及降压药物用量显著减少,体重、血糖、糖化血红蛋白以及胰岛素抵抗指标均显著下降,DNⅢ期和Ⅳ期糖尿病缓解率分别为83.9%和77.8%。手术前、后肾功能无显著变化,24 h尿蛋白(正常值为<30 mg/24 h)各组均有下降, DNⅢ期于术后1年恢复至正常水平[(78.68±58.48) mg/24 h 比(17.67±14.45) mg/24 h, P<0.001],DNⅣ期组较术前持续降低[(1143.51±969.68) mg/24 h 比(493.57±725.72) mg/24 h, P>0.05]。结论:胃旁路术对2型糖尿病合并肥胖有显著减重、降糖的疗效,且有缓解DN进展的可能。%Objective To investigate the short-term effect of gastric bypass on diabetic nephropathy (DN). Methods A retrospective study was done of 58 obese patients with DN stage ⅢtoⅣperformed Roux-en-Y gastric bypass. The surgical effects on type 2 diabetes mellitus (T2DM), blood pressure, renal function and albuminuria were analyzed with one year follow-up. Results There was significant reduction of medication use for diabetes and hypertension after one year of surgery. The weight, blood glucose level, glycosylated haemoglobin A1c (HbA1c) and insulin resistance reduced significantly compared with those preoperative. Remission of T2DM of DN stage Ⅲ and Ⅳ were 83.9% and 77.8% respectively. Renal function profile had no significant difference before and after surgery. Preoperative albuminuria level in DN stage Ⅲ reduced to normal [(78.68±58.48) mg/24 h vs (17.67±14.45) mg/24 h, P0.05. Conclusions Gastric bypass shows the great improve-ment of T2DM with obesity and DN.

  13. Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

    International Nuclear Information System (INIS)

    Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m2) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie–Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response

  14. Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin.

    Science.gov (United States)

    Munusamy, Shankar; do Carmo, Jussara M; Hosler, Jonathan P; Hall, John E

    2015-10-15

    We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R-/-), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R-/- mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R-/- mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R-/- mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin.

  15. Control of type 2 diabetes in King Abdulaziz Housing City (Iskan population, Saudi Arabia

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    Thamer A Alsulaiman

    2016-01-01

    Full Text Available Objective: To assess the level of control and prevalence of type 2 diabetes in King Abdulaziz Housing City (Iskan population of Saudi Arabia. Materials and Methods: Retrospective cross-sectional study conducted in a primary-care setting. All Type 2 diabetics referred to our diabetes center between January 2011 and January 2015 were identified, and their computerized records reviewed. Glycated hemoglobin levels (HbA1c, low-density lipoprotein (LDL, blood pressure (BP, and the albumin-creatinine ratio (ACR were noted and the patients categorized accordingly. Demographic data (age and gender were also documented. Inactive patients (not seen for more than 2 years were excluded. Results: The overall prevalence of type 2 diabetes for all age groups in ISKAN population was 3.25%. About 56% of the diabetics were female and 70% were aged between 18 and 59 years. The rate of uncontrolled diabetes was 59.3%. Males were more likely to have uncontrolled diabetes (odds ratio: 1.44, CI: 1.17-1.76, P = 0.0004. Forty percent of the diabetics had an LDL above target (≥2.6 mmol/l while 25.9% had uncontrolled hypertension (BP ≥ 140/90 mmHg. Of those who had an ACR test done within the last year (59.3%, the rate of micro- and macro-albuminuria was 8.8% and 2.5%, respectively. Conclusions: The overall prevalence of type 2 diabetes in our community seems lower than the previously reported national figures. An alarming number of diabetics in our population have an uncontrolled disease. More stringent diabetes annual review and recall program is needed to control diabetes and reduce complications.

  16. Serum Lipid Profiles, Lipid Ratios and Chronic Kidney Disease in a Chinese Population

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    Liying Zhang

    2014-07-01

    Full Text Available Aim: To examine the association of serum lipids, lipid ratios with Chronic Kidney Disease (CKD in a Chinese population. Methods: Data were drawn from a cross-sectional survey in China. CKD was defined as estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2 or albuminuria-to-creatinine ratio (ACR > 30 mg/g. Multivariable logistic regressions and multivariate regression models were used. Serum lipids and lipid ratios included total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio. Results: In men, only logarithm-transformed (log TG was associated with CKD. The odds ratio (every SD increment was 1.39 (95% CI 1.03–1.87, P = 0.03. In women, none of the serum lipids and lipid ratios was associated with CKD. Using multivariate regression models, it was shown that log TG and log TG/HDL-C were negatively correlated with eGFR (P < 0.05 in men and LDL-C and log LDL-C/HDL-C ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05. All of serum lipid profiles and lipid related ratio were not correlated with ACR in women. Conclusion: Serum TG is the only suitable predictor for CKD in men. However, in women, none of serum lipids and lipid ratio can be used as a predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in both genders.

  17. Assessment of microalbuminuria for early diagnosis and risk prediction in dengue infections.

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    Nguyen Thi Hanh Tien

    Full Text Available BACKGROUND: Dengue is the most important arboviral infection of humans. Following an initial febrile period, a small proportion of infected patients develop a vasculopathy, with children at particular risk for severe vascular leakage and shock. Differentiation between dengue and other common childhood illnesses is difficult during the early febrile phase, and risk prediction for development of shock is poor. The presence of microalbuminuria is recognized as a useful early predictor for subsequent complications in a number of other disorders with vascular involvement. Significant proteinuria occurs in association with dengue shock syndrome and it is possible that early-phase microalbuminuria may be helpful both for diagnosis of dengue and for identification of patients likely to develop severe disease. METHODOLOGY/PRINCIPAL FINDINGS: We measured formal urine albumin to creatinine ratios (UACRs in daily samples obtained from a large cohort of children with suspected dengue recruited at two outpatient clinics in Ho Chi Minh City, Vietnam. Although UACRs were increased in the 465 confirmed dengue patients, with a significant time trend showing peak values around the critical period for dengue-associated plasma leakage, urine albumin excretion was also increased in the comparison group of 391 patients with other febrile illnesses (OFI. The dengue patients generally had higher UACRs than the OFI patients, but microalbuminuria, using the conventional cutoff of 30 mg albumin/g creatinine discriminated poorly between the two diagnostic groups in the early febrile phase. Secondly UACRs did not prove useful in predicting either development of warning signs for severe dengue or need for hospitalization. CONCLUSION/SIGNIFICANCE: Low-level albuminuria is common, even in relatively mild dengue infections, but is also present in many OFIs. Simple point-of-care UACR tests are unlikely to be useful for early diagnosis or risk prediction in dengue endemic areas.

  18. Sirolimus therapy to halt the progression of ADPKD.

    Science.gov (United States)

    Perico, Norberto; Antiga, Luca; Caroli, Anna; Ruggenenti, Piero; Fasolini, Giorgio; Cafaro, Mariateresa; Ondei, Patrizia; Rubis, Nadia; Diadei, Olimpia; Gherardi, Giulia; Prandini, Silvia; Panozo, Andrea; Bravo, Rodolfo Flores; Carminati, Sergio; De Leon, Felipe Rodriguez; Gaspari, Flavio; Cortinovis, Monica; Motterlini, Nicola; Ene-Iordache, Bogdan; Remuzzi, Andrea; Remuzzi, Giuseppe

    2010-06-01

    Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.

  19. Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators) - A pilot study

    International Nuclear Information System (INIS)

    There are no available data about the prevalence of chronic kidney disease (CKD) and its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and blood and urine samples were collected. Participants were categorized to their CKD stage according to their estimated Modification of Diet in Renal Disease (MDRD3)-based, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the presence of albuminuria. The sample comprised 491 (49.9% were males) adult Saudi nationals. The mean age was 37.4 ± 11.3 years. The overall prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mellitus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD. Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients (Author).

  20. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

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    Katalin Susztak

    2005-02-01

    Full Text Available BACKGROUND: Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood. METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis. CONCLUSION: Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  1. Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1.

    Science.gov (United States)

    Khan, Shenaz; Lakhe-Reddy, Sujata; McCarty, Joseph H; Sorenson, Christine M; Sheibani, Nader; Reichardt, Louis F; Kim, Jane H; Wang, Bingcheng; Sedor, John R; Schelling, Jeffrey R

    2011-02-01

    Integrins are heterodimeric receptors that regulate cell adhesion, migration, and apoptosis. Integrin αvβ8 is most abundantly expressed in kidney and brain, and its major ligand is latent transforming growth factor-β (TGF-β). Kidney αvβ8 localizes to mesangial cells, which appose glomerular endothelial cells and maintain glomerular capillary structure by mechanical and poorly understood paracrine mechanisms. To establish kidney αvβ8 function, mice with homozygous Itgb8 deletion (Itgb8(-/-)) were generated on outbred and C57BL/6 congenic backgrounds. Most Itgb8(-/-) mice died in utero, and surviving Itgb8(-/-) mice failed to gain weight, and rarely survived beyond 6 weeks. A renal glomerular phenotype included azotemia and albuminuria, as well as increased platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, which was surprisingly not associated with conventional functions, such as endothelial cell hyperplasia, hypertrophy, or perivascular inflammation. Itgb8(-/-) mesangial cells demonstrated reduced latent TGF-β binding, resulting in bioactive TGF-β release, which stimulated glomerular endothelial cell apoptosis. Using PECAM-1 gain and loss of function strategies, we show that PECAM-1 provides endothelial cytoprotection against mesangial cell TGF-β. These results clarify a singular mechanism of mesangial-to-endothelial cell cross-talk, whereby mesangial cell αvβ8 homeostatically arbitrates glomerular microvascular integrity by sequestering TGF-β in its latent conformation. Under pathological conditions associated with decreased mesangial cell αvβ8 expression and TGF-β secretion, compensatory PECAM-1 modulation facilitates glomerular endothelial cell survival.

  2. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis.

    Science.gov (United States)

    Khan, Shenaz; Abu Jawdeh, Bassam G; Goel, Monu; Schilling, William P; Parker, Mark D; Puchowicz, Michelle A; Yadav, Satya P; Harris, Raymond C; El-Meanawy, Ashraf; Hoshi, Malcolm; Shinlapawittayatorn, Krekwit; Deschênes, Isabelle; Ficker, Eckhard; Schelling, Jeffrey R

    2014-03-01

    Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding. Kidneys from mouse models of progressive, albuminuric kidney disease exhibited increased fatty acids, LC-CoAs, and caspase-2-dependent proximal tubule lipoapoptosis. LC-CoAs and the cytosolic domain of NHE1 directly interacted, with an affinity comparable to that of the PI(4,5)P2-NHE1 interaction, and competing LC-CoAs disrupted binding of the NHE1 cytosolic tail to PI(4,5)P2. Inhibition of LC-CoA catabolism reduced NHE1 activity and enhanced apoptosis, whereas inhibition of proximal tubule LC-CoA generation preserved NHE1 activity and protected against apoptosis. Our data indicate that albuminuria/lipiduria enhances lipotoxin delivery to the proximal tubule and accumulation of LC-CoAs contributes to tubular atrophy by severing the NHE1-PI(4,5)P2 interaction, thereby lowering the apoptotic threshold. Furthermore, these data suggest that NHE1 functions as a metabolic sensor for lipotoxicity.

  3. Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin.

    Science.gov (United States)

    Munusamy, Shankar; do Carmo, Jussara M; Hosler, Jonathan P; Hall, John E

    2015-10-15

    We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R-/-), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R-/- mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R-/- mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R-/- mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin. PMID:26290368

  4. Circulating adipocytokines and chronic kidney disease.

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    Katherine T Mills

    Full Text Available BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD, but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m(2 or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001 and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001 were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9 for leptin and 12.7 (6.5, 24.6 for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6. In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

  5. Association Between Prescription Opioid Use and Biomarkers of Kidney Disease in US Adults

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    Celestina Barbosa-Leiker

    2016-06-01

    Full Text Available Background/Aims: Prescription opioid use is increasing despite concerns about drug safety. We examined relationships between use of analgesics with biomarkers of chronic kidney disease (CKD in a representative sample of adults in the United States (US. Methods: Participants (n=3980 were from the National Health and Nutrition Examination Survey (NHANES 2009-2010. Use of any analgesic, prescription opioids, and NSAIDs were compared to referent groups with use of non-analgesic prescription medication or use of no prescription medication. CKD biomarkers including urine albumin-to-creatinine ratio (UACR and serum-creatinine-based estimated glomerular filtration rate (eGFR; CKD Epidemiology Collaboration: CKD-EPI equation were analyzed as continuous and binary variables (UACR ≥30 mg/g or eGFR 2; median splits. Results: Frequencies of use were: any prescription analgesic 12.7% (507/3980; prescription opioids 5.1% (204/3980; NSAIDs 5.6% (224/3980; non-analgesic medication 38.7% (1540/3980; no medication 48.6% (1933/3980. Prescription analgesic use (β=0.17, p=0.021 and opioid use (β=0.19, p=0.002 were associated with higher UACR values, while NSAID use was not (β=0.17, p=0.105. Prescription analgesic use was related to UACR ≥5.98 mg/g (median, (OR=1.34, 95%CI=1.01-7.79, p=0.045. No type of analgesic use was related to CKD-EPI eGFR. Conclusion: In a representative US population, prescription opioid use associated with higher albuminuria levels compared to non-opioid-users.

  6. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

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    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

  7. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

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    Luo, Xiaoyan

    2011-11-01

    Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-\\/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg\\/dl) was prevented for >6 months by the dsAAV2\\/7, dsAAV2\\/8, and dsAAV2\\/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2\\/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2\\/7 and dsAAV2\\/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2\\/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-\\/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2\\/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2\\/9 vector. Hepatorenal correction in G6pase (-\\/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

  8. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice.

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    Gai, Zhibo; Gui, Ting; Hiller, Christian; Kullak-Ublick, Gerd A

    2016-01-29

    Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nuclear bile acid receptor in the prevention of diabetic nephropathy and obesity-induced renal damage. Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice that had undergone uninephrectomy, a model resembling the clinical situation of kidney donation by obese individuals. Mice fed a high-fat diet developed the core features of metabolic syndrome, with subsequent renal lipid accumulation and renal injury, including glomerulosclerosis, interstitial fibrosis, and albuminuria. The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was more prominent in the proximal tubules of 15 obese patients compared with 16 non-obese patients. In mice treated with the FXR agonist obeticholic acid, renal injury, renal lipid accumulation, apoptosis, and changes in lipid peroxidation were attenuated. Moreover, disturbed mitochondrial function was ameliorated and the mitochondrial respiratory chain recovered following obeticholic acid treatment. Culturing renal proximal tubular cells with free fatty acid and FXR agonists showed that FXR activation protected cells from free fatty acid-induced oxidative stress and endoplasmic reticulum stress, as denoted by a reduction in the level of reactive oxygen species staining and Grp78 immunostaining, respectively. Several genes involved in glutathione metabolism were induced by FXR activation in the remnant kidney, which was consistent with a decreased glutathione disulfide/glutathione ratio. In summary, FXR activation maintains endogenous glutathione homeostasis and protects the kidney in uninephrectomized mice from obesity-induced injury. PMID:26655953

  9. Gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes

    International Nuclear Information System (INIS)

    To determine the relationship of insulin resistance with microalbuminuria in patients of type-2 Diabetes mellitus and observe gender difference if any. Study Design: A cross-sectional study. Place and Duration of Study: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to August 2007. Methodology: One hundred and fifty five patients of type-2 Diabetes mellitus were included in the study who had either microalbuminuria or normo albuminuria. Body mass index, waist circumference and blood pressure were recorded. Fasting venous blood sample was collected for plasma glucose (FPG), serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c. Urine albumin excretion was determined using urine albumin to creatinine ratio. Insulin resistance was calculated from fasting plasma glucose and serum insulin levels, using homeostatic model assessment of insulin resistance (HOMA-IR). Correlation and association testing was carried out with significance at p < 0.05. Results: Microalbuminuria was found to be significantly correlated with HOMA-IR (r = 0.33, p < 0.001), serum insulin (r = 0.28, p = < 0.001), body mass index (r = 0.18, p = 0.02) and waist circumference (r = 0.21, p = 0.008). This correlation was more significant in women (n = 85, r = 0.48, p = < 0.0001) as compared to men (n = 70, r = 0.14, p = 0.12). The correlation between HOMA-IR and urine albumin excretion remained highly significant (p = 0.001) after controlling for gender, age, duration of diabetes, waist circumference, hypertension, triglycerides and HbA1c. Conclusion: Urinary albumin excretion in patients of type-2 diabetes is strongly associated with insulin resistance and related cardiovascular risk factors. This association appears to be stronger in women than the men, in our population. (author)

  10. Frequency of Microalbuminuria in Type 1 Diabetic Children

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    Somayeh Sahari

    2009-12-01

    Full Text Available Objective: Diabetic nephropathy is a serious complication of type 1 diabetes which involves one third of the patients. The aim of this study was to estimate the frequency of microalbuminuria in type 1 diabetic patients visited in Pediatric Endocrine Clinic in Hamedan, west province of Iran, in 2007.Methods: Diabetic patients visited in Pediatric Diabetes Clinic were enrolled in the study. Variable data such as age, sex, duration of the disease, stage of puberty, dose of insulin/kg/day, and blood pressure of the patients were obtained according to history and physical examination. 24h urine samples were collected for protein, creatinine, and microalbumin. Data analysis was assessed using independent t-test and chi-square test.Findings: One-hundred five patients (56 females and 49 males with a mean age of 13.3±5.5 years, were evaluated. Fifteen (14.3% cases had microalbuminuria. Mean age in microalbuminuric group was 16.2±2.8, and in non-microalbuminuric group was 12.7±5.6 years (P=0.024. Mean duration of diabetes was 9.1±3.2 yr in microalbuminuric and 4.5± 3.9 in non-microalbuminuric group. There was a significant correlation between duration of diabetes and microalbuminuria (P<0.001. Blood pressure was normal in 95.5% of the patients while in patients with microalbuminuria 73.3% had hypertension (P<0.001. Frequency of micro­albuminuria was higher in patients taking lower doses of insulin corrected to their body weight (P=0.008.Conclusion: Frequency of microalbuminuria was significant, so regular screening is highly recommended for early detection and timely treatment of diabetic nephropathy in order to prevent progression to end stage renal disease

  11. Prevalence of chronic kidney disease and prediabetes and associated risk factors: a community-based screening in Zhuhai, Southern China

    Institute of Scientific and Technical Information of China (English)

    GU Dong-feng; SHI Yan-lin; CHEN You-ming; LIU Hong-mei; DING Ya-nan; LIU Xin-yu; LI Yong-qiang

    2013-01-01

    Background The prevalence of chronic kidney disease (CKD) and prediabetes has increased in China,and at different rates in different locations.Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes,and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.Methods A total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method.An estimated glomerular filtration rate (eGFR),albuminuria,fasting plasma glucose (FPG),and homeostatic model assessment of insulin resistance (HOMA-IR) were measured.Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006.Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes,and association of insulin resistance (IR) with CKD and prediabetes was analyzed.Results The age-standardized prevalence of CKD was 12.5%,eGFR <60 ml.min-1.1.73 m-2 was 2.7% and ACR (albumin to creatinine ratio) >30 mg/g was 10.3%.The age-standardized prevalence of prediabetes was 12.1%.Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes.Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.Conclusion CKD and prediabetes have become a major public health problem in Zhuhai,Southern China; insulin resistance may be an important risk factor.

  12. A new mouse model to explore therapies for preeclampsia.

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    Abdulwahab Ahmed

    Full Text Available BACKGROUND: Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE. DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF signaling by soluble VEGF receptor 1 (sFlt-1 is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. CONCLUSIONS/SIGNIFICANCE: We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

  13. P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

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    Adelson M Rodrigues

    Full Text Available Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7 receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v. and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L. By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3'-O-(4-benzoylbenzoyl adenosine5'-triphosphate (specific agonist and adenosine triphosphate (nonspecific agonist (all p<0.05. All these alterations were reduced in diabetic rats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy in DM groups. Lipoperoxidation was strongly correlated with P2X(7 receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7 receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy.

  14. Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1α in db/db mice.

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    Yu Ah Hong

    Full Text Available Peroxisome proliferator-activated receptor (PPAR-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK, and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α-estrogen-related receptor (ERR-1α-phosphorylated acetyl-CoA carboxylase (pACC, and suppression of sterol regulatory element-binding protein (SREBP-1 and carbohydrate regulatory element-binding protein (ChREBP-1, key downstream effectors of lipid metabolism. Fenofibrate decreased the activity of phosphatidylinositol-3 kinase (PI3K-Akt phosphorylation and FoxO3a phosphorylation in kidneys, increasing the B cell leukaemia/lymphoma 2 (BCL-2/BCL-2-associated X protein (BAX ratio and superoxide dismutase (SOD 1 levels. Consequently, fenofibrate recovered from renal apoptosis and oxidative stress, as reflected by 24 hr urinary 8-isoprostane. In cultured mesangial cells, fenofibrate prevented high glucose-induced apoptosis and oxidative stress through phosphorylation of AMPK, activation of PGC-1α-ERR-1α, and suppression of SREBP-1 and ChREBP-1. Our results suggest that fenofibrate improves lipotoxicity via activation of AMPK-PGC-1α-ERR-1α-FoxO3a signaling, showing its potential as a therapeutic modality for diabetic nephropathy.

  15. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice.

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    Wu, Jin; Guan, Tian-jun; Zheng, Shirong; Grosjean, Fabrizio; Liu, Weicheng; Xiong, Huabao; Gordon, Ronald; Vlassara, Helen; Striker, Gary E; Zheng, Feng

    2011-10-01

    Inflammation has a key role in diabetic nephropathy (DN) progression. Pentosan polysulfate (PPS) has been shown to decreases interstitial inflammation and glomerulosclerosis in 5/6 nephrectomized rats. Since PPS has an excellent long-term safety profile in interstitial cystitis treatment, and we recently found that old diabetic C57B6 mice develop DN characterized by extensive tubulointerstitial inflammatory lesions that mimics human DN, we examined the effect of PPS on old diabetic mice. We also examined the anti-inflammatory properties of PPS in renal cells in vitro. Diabetes was induced with streptozotocin in 18 months female (early aging) C57B6 mice. Mice were then randomized to receive oral PPS (25 mg/kg/day) or water for 4 months. The effect of PPS on NF-κB activation and on TNFα, high glucose or advanced glycation end products (AGEs) stimulated proinflammatory gene expression in renal cells was examined. We found that PPS treatment preserved renal function, significantly reduced albuminuria, and markedly decreased the severity of renal lesions, including tubulointerstitial inflammation. PPS also reduced upregulation of TNFα and proinflammatory genes in aging diabetic kidneys. Furthermore, PPS suppressed NF-κB, decreased the proinflammatory actions of TNFα, and decreased high glucose and AGEs stimulated MCP-1 production in vitro. Finally, PPS decreased TNFα-induced increase in albumin permeability in podocyte monolayers. In conclusion, PPS treatment largely prevents the development/progression of nephropathy in aging diabetic mice. As this may be mediated by suppression of TNFα, high glucose, and AGE-stimulated NF-κB activation and inflammation in vitro, the in vivo blockade of DN may be due to the anti-inflammatory properties of PPS.

  16. Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment-resistant hypertension.

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    Oxlund, Christina S; Buhl, Kristian B; Jacobsen, Ib A; Hansen, Mie R; Gram, Jeppe; Henriksen, Jan Erik; Schousboe, Karoline; Tarnow, Lise; Jensen, Boye L

    2014-12-01

    In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria/proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase-type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen-to-plasmin activation; and (3) inhibits urine urokinase-type plasminogen activator in patients with resistant hypertension and type 2 diabetes mellitus (T2DM).In an open-label, non-randomized, 8-week intervention study, a cohort (n = 80) of patients with resistant hypertension and T2DM were included. Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin-angiotensin-aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks. Complete dataset for urine analysis was available in 60 patients. Systolic and diastolic BP measured by ambulatory BP monitoring and office monitoring were significantly reduced. Average daytime BP was reduced by 6.3/3.0 mm Hg. Seven of 80 cases (9%) discontinued amiloride due to hyperkalemia >5.5 mol/L, the most frequent adverse event. Urinary plasmin(ogen) and albumin excretions were significantly reduced after amiloride treatment (P treatment. Amiloride lowers BP, urine plasminogen excretion and activation, and albumin/creatinine ratio, and is a relevant add-on medication for the treatment of resistant hypertension in patients with T2DM and microalbuminuria.

  17. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

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    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  18. End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

    Institute of Scientific and Technical Information of China (English)

    Matthias; L?hn; Oliver; Plettenburg; Aimo; Kannt; Markus; Kohlmann; Armin; Hofmeister; Dieter; Kadereit; Peter; Monecke; Alexander; Schiffer; Anke; Schulte; Hartmut; Ruetten; Yuri; Ivashchenko

    2015-01-01

    AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.

  19. miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy

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    Yijie Jia

    2016-01-01

    Full Text Available Background. miR-192, miR-194, and miR-215 are enriched in the kidney and play roles in the pathogenesis of diabetic nephropathy (DN. Extracellular vesicles (EVs can be detected in body fluids and may serve as disease biomarkers. Methods. Eighty type 2 diabetes patients with normoalbuminuria (n=30, microalbuminuria (n=30, or macroalbuminuria (n=20, as well as 10 healthy controls, were enrolled in this study. Real-time PCR was used to evaluate urinary EV miRNAs expression. Results. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. In patients with normoalbuminuria and microalbuminuria, miR-192 was positively correlated with albuminuria (r=0.357, P=0.005 levels and transforming growth factor- (TGF- β1 (r=0.356, P=0.005 expression. Receiver operating characteristic (ROC curve analysis revealed that miR-192 was better than miR-194 and miR-215 in discriminating the normoalbuminuric group from the microalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. Conclusion. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN.

  20. Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy.

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    Alaa Alkhalaf

    Full Text Available BACKGROUND: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN, urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66. Controls were matched for gender and diabetes duration (n = 82. METHODOLOGY/PRINCIPAL FINDINGS: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS. Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978. Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. CONCLUSIONS: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.

  1. Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus.

    Science.gov (United States)

    Genevieve, M; Vivot, A; Gonzalez, C; Raffaitin, C; Barberger-Gateau, P; Gin, H; Rigalleau, V

    2013-09-01

    As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA1c levels measured every 6months as far back as the last 5years were also collected. The association of AF with the patients' past glucose control, based on their latest HbA1c values, and the means of the last five and 10 HbA1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th-75th percentiles: 1.7-2.4] arbitrary units (AU), and this was associated with age (β=0.15 per 10years, P<0.001) and diabetes duration (β=0.17 per 10years, P<0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA1c values (β=0.10 per 1% of HbA1c, P=0.005, and β=0.13 per 1% of HbA1c, P=0.001, respectively). In addition, the skin AF was associated with retinopathy (P<0.001), albuminuria (P<0.001) and decreased eGFR (P<0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications. PMID:23643347

  2. Association of Microalbuminuria and Estimated Glomerular Filtration Rate With Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus

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    Dehdashti Shahrokh

    2015-04-01

    Full Text Available Background Atherosclerosis is the main cause of cardiovascular diseases, and its risk enhances in type 2 diabetes mellitus. Objectives This study aimed to evaluate Carotid Intima-Media Thickness (CIMT by carotid artery ultrasonography and assess its correlation with microalbuminuria and estimated Glomerular Filtration Rate (eGFR in the patients with type 2 diabetes mellitus. Patients and Methods This cross-sectional study was included 205 patients with Type 2 Diabetes Mellitus (T2DM. We recorded clinical and biochemical data such as FBS, lipid profile, and urinary albumin. Intima-media thickness of carotid arteries was measured in all patients by high frequency ultrasound. Results In simple correlation coefficients analysis, CIMT was significantly associated with total cholesterol (r = 0.197, P = 0.008, serum creatinine (r = 0.240, P = 0.001, and urinary albumin (r = 0.420, P = 0.000. Also, CIMT elevated significantly with the stage progression of chronic kidney disease (0.67 ± 0.15 mm in stage 1, 0.73 ± 0.22 mm in stage 2, and 0.82 ± 0.21 mm in stage 3 (P value = 0.024. In multivariate linear regression analysis, the duration of diabetes, weight, HDL, serum creatinine, urinary albumin, and estimated Glomerular Filtration Rate (eGFR were independently associated with CIMT (P value < 0.05 for all. Conclusions Our study shows a relationship between CIMT and renal parameters, including eGFR and albuminuria. This study confirms the importance of intensive examinations for early detection of atherosclerosis and treatment of risk factors.

  3. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

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    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. PMID:27431456

  4. Serum galectin-3: a risk factor for vascular complications in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    JIN Qi-hui; LOU Yu-feng; LI Tian-lang; CHEN Huai-hong; LIU Qiang; HE Xiao-jun

    2013-01-01

    Background Plasma galectin-3,a mediator of fibrogenesis and inflammation,its potential to associate with type 2 diabetes (T2DM) is poorly investigated.Here,we explored its interaction with the serum galectin-3 and vascular complications.Methods We conducted a population-based cross-sectional survey in Zhejiang,China involving 165 men and 119 women (age range,43-84 years),investigating the relationship between serum galectin-3 and vascular disease in patients with T2DM.Results Serum galectin-3 was higher in subjects with T2DM than that in control participants (27.4 vs.17.6 ng/ml,P <0.001).Compared with subjects with galectin-3 values in the lowest quartile,those with values in the highest quartile had an increased likelihood of vascular complications (4th quartile odds ratio (OR) 2.52,95% confidence interval (CI),1.25-4.07).Increased risk of micro-or macrovascular complications corrrelated with serum galectin-3 concentration (ORs 11.4and 8.5,respectively).An increased number of vascular complications was associated with high serum galectin-3 levels (P<0.05).Patients with serum galectin-3 levels >25 ng/ml had an elevated risk of diabetes relative to patients with levels <10ng/ml (OR for any vascular complication 2.64,for heart failure 3.97,for nephropathy 4.09,for peripheral arterial disease (PAD) 4.18; all P <0.05).Complication risk was higher in patients with neurogenic,stroke,or retinopathy complications,but this difference was not significant after risk factor adjustment.Serum galectin-3 levels correlated with diabetes duration,C-reactive protein (CRP) levels,and albuminuria.Conclusion High galectin-3 values were associated with increased odds of developing heart failure,nephropathy,and peripheral arterial disease in patients with T2DM.

  5. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway.

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    Kuo-Feng Hua

    Full Text Available Renal reactive oxygen species (ROS and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation of IgA nephropathy (IgAN, which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L. Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1 reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2 inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3 decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4 inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5 inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

  6. The goal of blood pressure in the hypertensive patient with diabetes is defined: now the challenge is go from recommendations to practice.

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    Lopez-Jaramillo, Patricio; Lopez-Lopez, Jose; Lopez-Lopez, Cristina; Rodriguez-Alvarez, Miguel I

    2014-01-01

    The recent Latin American and European guidelines published this year has proposed as a goal for blood pressure control in patients with diabetes type 2 a value similar or inferior to 140/90 mmHg. High blood pressure is the leading cause of cardiovascular diseases and deaths globally. Although once hypertension is detected, 80% of individuals are on a pharmacologic therapy only a minority is controlled. Diabetes also is a risk factor for other serious chronic diseases, including cardiovascular disease. Whether specifically targeting lower fasting glucose levels can reduce cardiovascular outcomes remains unknown. Hypertension is present in 20% to 60% of patients with type 2 diabetes, depending on age, ethnicity, obesity, and the presence of micro or macro albuminuria. High blood pressure substantially increases the risk of both macro and micro vascular complications, doubling the risk of all-cause mortality and stroke, tripling the risk of coronary heart disease and significantly hastening the progression of diabetic nephropathy, retinopathy, and neuropathy. Thus, blood pressure lowering is a major priority in preventing cardiovascular and renal events in patients with diabetes and hypertension. During many years the BP goals recommended in patients with diabetes were more aggressive than in patients without diabetes. As reviewed in this article many clinical trials have demonstrated not only the lack of benefits of lowering the BP below 130/80 mmHg, but also the J-shaped relationship in DM patients. Overall we discuss the importance of define the group of patients in whom significant BP reduction could be particularly dangerous and, on the other hand, those with a high risk of stroke who could benefit most from an intensive hypotensive therapy. In any case, the big challenge now is avoid the therapeutic inertia (leaving diabetic patients with BP values of 140/90 mmHg or higher) at all costs, as this would lead to an unacceptable toll in terms of human lives

  7. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy.

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    Kim, Su-Mi; Lee, Sang-Ho; Kim, Yang-Gyun; Kim, Se-Yun; Seo, Jung-Woo; Choi, Young-Wook; Kim, Dong-Jin; Jeong, Kyung-Hwan; Lee, Tae-Won; Ihm, Chun-Gyoo; Won, Kyu-Yeoun; Moon, Ju-Young

    2015-05-01

    IL-1β-secreting nucleotide-binding oligomerization domain protein 3 (NLRP3) inflammasomes play a pivotal role in triggering innate immune responses in metabolic disease. We investigated the role of soluble uric acid in NLRP3 inflammasome activation in macrophages to demonstrate the effect of systemic hyperuricemia on progressive kidney damage in type 2 diabetes. THP-1 cells, human acute monocytic leukemia cells, were cultured to obtain macrophages, and HK-2 cells, human renal proximal tubule cells, were cultured and stimulated with uric acid. In vivo, we designed four rat groups as follows: 1) Long-Evans Tokushima Otsuka (LETO); 2) Otsuka Long-Evans Tokushima Fatty (OLETF); 3) OLETF+high-fructose diet (HFD) for 16 wk; and 4) OLETF+HFD+allopurinol (10 mg/dl administered in the drinking water). Soluble uric acid stimulated NLRP3 inflammasomes to produce IL-1β in macrophages. Uric acid-induced MitoSOX mediates NLRP3 activation and IL-1β secretion. IL-1β from macrophages activates NF-κB in cocultured proximal tubular cells. In vivo, intrarenal IL-1β expression and macrophage infiltration increased in HFD-fed OLETF rats. Lowering the serum uric acid level resulted in improving the albuminuria, tubular injury, macrophage infiltration, and renal IL-1β (60% of HFD-fed OLETF) independently of glycemic control. Direct activation of proximal tubular cells by uric acid resulted in (C-X-C motif) ligand 12 and high mobility group box-1 release and accelerated macrophage recruitment and the M1 phenotype. Taken together, these data support direct roles of hyperuricemia in activating NLRP3 inflammasomes in macrophages, promoting chemokine signaling in the proximal tubule and contributing to the progression of diabetic nephropathy through cross talk between macrophages and proximal tubular cells. PMID:25651569

  8. Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.

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    Cowley, Allen W; Yang, Chun; Zheleznova, Nadezhda N; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P; Skelton, Meredith M; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

    2016-02-01

    This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the ≈68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134±5 versus 151±3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (Pblood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4.

  9. [Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care].

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    Faller, J; Hess, B

    2002-05-01

    Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.

  10. Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model

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    Mi Young Lee

    2011-04-01

    Full Text Available BackgroundWhile there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.MethodsThirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5, spironolactone-treated (n=10, losartan-treated (n=9, and combination of spironolactone- and losartan-treated (n=9.ResultsAt week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.ConclusionThese results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

  11. Dietary fish oil reduces glomerular injury and elevated renal hydroxyeicosatetraenoic acid levels in the JCR:LA-cp rat, a model of the metabolic syndrome.

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    Aukema, Harold M; Lu, Jing; Borthwick, Faye; Proctor, Spencer D

    2013-07-14

    We have previously shown nutritional intervention with fish oil (n-3 PUFA) to reduce numerous complications associated with the metabolic syndrome (MetS) in the JCR:LA-corpulent (cp) rat. In the present study, we sought to explore the potential role of fish oil to prevent glomerulosclerosis in JCR:LA-cp rats via renal eicosanoid metabolism and lipidomic analysis. Male lean and MetS JCR:LA-cp rats were fed a lipid-balanced diet supplemented with fish oil (5 or 10 % of total fat). After 16 weeks of feeding, albuminuria was significantly reduced in MetS rats supplemented with 5 or 10 % fish oil ( - 53 and - 70 %, respectively, compared with the untreated MetS rats). The 5 % fish oil diet resulted in markedly lower glomerulosclerosis ( - 43 %) in MetS rats and to a lesser extent in those supplemented with 10 % fish oil. Interestingly, untreated MetS rats had higher levels of 11- and 12-hydroxyeicosatetraenoic acids (HETE) v. lean rats. Dietary fish oil reduced these levels, as well as other (5-, 9- and 15-) HETE. Whilst genotype did not alter prostanoid levels, fish oil reduced endogenous renal levels of 6-keto PGF1α (PGI2 metabolite), thromboxane B2 (TxB2), PGF2α and PGD2 by approximately 60 % in rats fed 10 % fish oil, and TxB2 ( - 50 %) and PGF2α ( - 41 %) in rats fed 5 % fish oil. In conclusion, dietary fish oil prevented glomerular damage in MetS rats and mitigated the elevation in renal HETE levels. These results suggest a potential role for dietary fish oil to improve dysfunctional renal eicosanoid metabolism associated with kidney damage during conditions of the MetS.

  12. Natural Killer Cell Reduction and Uteroplacental Vasculopathy.

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    Golic, Michaela; Haase, Nadine; Herse, Florian; Wehner, Anika; Vercruysse, Lisbeth; Pijnenborg, Robert; Balogh, Andras; Saether, Per Christian; Dissen, Erik; Luft, Friedrich C; Przybyl, Lukasz; Park, Joon-Keun; Alnaes-Katjavivi, Patji; Staff, Anne Cathrine; Verlohren, Stefan; Henrich, Wolfgang; Muller, Dominik N; Dechend, Ralf

    2016-10-01

    Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth. PMID:27550919

  13. Linagliptin Limits High Glucose Induced Conversion of Latent to Active TGFß through Interaction with CIM6PR and Limits Renal Tubulointerstitial Fibronectin.

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    Muralikrishna Gangadharan Komala

    Full Text Available In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4 inhibitors have been shown to be antifibrotic. We have previously shown that cation independent mannose-6-phosphate receptor (CIM6PR facilitates the conversion of latent to active transforming growth factor β1 (GFß1 in renal proximal tubular cells (PTCs and linagliptin (a DPP4 inhibitor reduced this conversion with downstream reduction in fibronectin transcription.We wanted to demonstrate that linagliptin reduces high glucose induced interaction between membrane bound DPP4 and CIM6PR in vitro and demonstrate reduction in active TGFß mediated downstream effects in a rodent model of type 1 diabetic nephropathy independent of high glycaemic levels.We used human kidney 2 (HK2 cells and endothelial nitric oxide synthase knock out mice to explore the mechanism and antifibrotic potential of linagliptin independent of glucose lowering. Using a proximity ligation assay, we show that CIM6PR and DPP4 interaction was increased by high glucose and reduced by linagliptin and excess mannose-6-phosphate (M6P confirming that linagliptin is operating through an M6P-dependent mechanism. In vivo studies confirmed these TGFß1 pathway related changes and showed reduced fibronectin, phosphorylated smad2 and phosphorylated smad2/3 (pSmad2/3 with an associated trend towards reduction in tubular atrophy, which was independent of glucose lowering. No reduction in albuminuria, glomerulosclerotic index or cortical collagen deposition was observed.Linagliptin inhibits activation of TGFß1 through a M6P dependent mechanism. However this in isolation is not sufficient to reverse the multifactorial nature of diabetic nephropathy.

  14. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

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    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis.

  15. High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

    Science.gov (United States)

    Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

    2015-11-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis.

  16. A molecular signature of proteinuria in glomerulonephritis.

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    Heather N Reich

    Full Text Available Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 "albumin-regulated genes" differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25 could be distinguished from those of control subjects (n = 6 based solely upon the expression of these 231 "albumin-regulated genes." The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33 can be distinguished from controls (n = 21 based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.

  17. The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

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    Davies, Melanie; Chatterjee, Sudesna; Khunti, Kamlesh

    2016-01-01

    Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of

  18. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  19. The dual role of complement in the progression of renal disease in NZB/W F(1) mice and alternative pathway inhibition.

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    Sekine, Hideharu; Ruiz, Phillip; Gilkeson, Gary S; Tomlinson, Stephen

    2011-10-01

    Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F(1) mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings. PMID:22000720

  20. Neonatal hypertension – a long-term pilot follow-up study

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    Chaudhari T

    2013-06-01

    Full Text Available Tejasvi Chaudhari,1 Michael C Falk,2,3 Rajeev Jyoti,2,4 Susan Arney,5 Wendy Burton,5 Alison L Kent1,2 1Department of Neonatology, Canberra Hospital, Woden, ACT, Australia; 2Australian National University Medical School, Canberra, ACT, Australia; 3Department of Nephrology, 4Medical Imaging Department, 5Centre for Newborn Care, Canberra Hospital, Woden, ACT, Australia Background: Neonatal hypertension occurs in up to 3% of neonates, more commonly in those admitted to neonatal intensive care. The aims of this study were to review renal function and renal volumes in children who had a history of neonatal hypertension. Methods: Children with a history of neonatal hypertension from January 2001 to December 2008 were included in the study during 2011. Blood pressure, weight, height, and body mass index were recorded. Renal ultrasound with 3D volume, urine for electrolytes, albumin, ß2 microglobulin, and blood for electrolytes, urea, creatinine, calcium, phosphate, renin, and aldosterone were collected depending on parental consent. Results: Of the 41 neonates with neonatal hypertension, eleven (27% were included in the study (six died; 24 moved interstate or declined involvement. One child (9% was still on antihypertensive medication and one was found to be hypertensive on review. This child had small volume kidneys and albuminuria. Three out of nine renal volume measurements were low (33% and two out of eleven had renal scarring (18%. The six available renin/aldosterone results were normal. Conclusion: This study suggests there are long-term renal and blood pressure implications for neonates with hypertension and ongoing surveillance of blood pressure and renal function should be performed throughout childhood and into early adulthood. Keywords: neonate, hypertension, renal ultrasound, 3D

  1. Diabetic nephropathy

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    Zelmanovitz Themis

    2009-09-01

    Full Text Available Abstract Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the

  2. Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus.

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    Genevieve, M; Vivot, A; Gonzalez, C; Raffaitin, C; Barberger-Gateau, P; Gin, H; Rigalleau, V

    2013-09-01

    As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA1c levels measured every 6months as far back as the last 5years were also collected. The association of AF with the patients' past glucose control, based on their latest HbA1c values, and the means of the last five and 10 HbA1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th-75th percentiles: 1.7-2.4] arbitrary units (AU), and this was associated with age (β=0.15 per 10years, P<0.001) and diabetes duration (β=0.17 per 10years, P<0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA1c values (β=0.10 per 1% of HbA1c, P=0.005, and β=0.13 per 1% of HbA1c, P=0.001, respectively). In addition, the skin AF was associated with retinopathy (P<0.001), albuminuria (P<0.001) and decreased eGFR (P<0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.

  3. Albumin contributes to kidney disease progression in Alport syndrome.

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    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

  4. The influence of nutrition (diet treatment in streptozotocin – induced diabetic rats

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    Chrcheva-Nikolovska Radmila

    2013-07-01

    Full Text Available The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups: group 1, control rats; group 2, antidiabetic diet group; group 3, rats with induced diabetes mellitus – diabetic control; group 4, rats with induced diabetes mellitus and diet food, and group 5, rats with induced diabetes mellitus and insulin treatment.A significant decrease in superoxide dismutase (SOD and total glutathione (GSH activities were observed in the liver of diabetic rats when compared with control animals. There was simple evidence that elevation in glucose concentration depress natural antioxidant defense such as SOD and GSH. The observed decrease in SOD activity could result from inactivation by H2O2 or by glycation of the enzyme, which have been reported to occur in diabetes. The possible source of oxidative stress in diabetes includes shifts in redox balance resulting from altered carbohydrate and lipid metabolism, increased generation of reactive oxygen species, and decreased level of antioxidant defences such as GSH and SOD. The plasma level of aminotransferases (ALT, AST, creatine kinase (CK, lactate dehydrogenase (LDH and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The decrease in total protein and albumin fraction may be due to microproteinuria and albuminuria, which are important clinical markers of diabetic nephro­pathy, and­/or may be due to increased protein catabolism.The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.

  5. Linagliptin: from bench to bedside

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    Doupis J

    2014-05-01

    Full Text Available John DoupisIatriko Palaiou Falirou Medical Center, Division of Diabetes, Athens, GreecePurpose: The nature of biomedical research affords a broad range of investigational topics at the preclinical stage, not all of which may be explored in subsequent clinical studies. To provide a comprehensive perspective on the physiologic effects of the dipeptidyl peptidase-4 inhibitor linagliptin, this review will discuss the results of both preclinical and clinical research, summarizing data describing outcomes associated with its use.Summary: Clinical studies demonstrate an overall favorable safety profile, low risk for hypoglycemia, weight neutrality, primarily nonrenal clearance, and efficacy for glycosylated hemoglobin reduction, typically ranging from 0.6% to 0.8% depending on baseline levels. In addition to these characteristics, preclinical research on linagliptin has yielded several interesting findings such as improved wound healing, reduced hepatic fat content, decreased infarct size following myocardial infarction or intracranial stroke, and improved vascular function with decreased oxidative stress. In accordance with its preclinical profile, linagliptin is unique among available dipeptidyl peptidase-4 compounds because it does not require dose adjustment when used in patients with renal dysfunction. Reduction of albuminuria with linagliptin on top of inhibitors of the renin–angiotensin–aldosterone system in both preclinical and post hoc clinical analysis serves as the foundation for ongoing clinical trials.Conclusion: In addition to its efficacy for glycemic control, current literature points to other potential opportunities associated with linagliptin therapy. These results warrant further investigation and underscore the importance of translational study based on findings from preclinical research. Moving forward, we can expect that future research on linagliptin and other incretin-based therapies will continue to expand their

  6. C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.

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    James A Shaw

    Full Text Available C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72 in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05. Reduction in albuminuria was also reported in the C-peptide group (p<0.05. In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001 reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05, glomerular volume (p<0.00001, and mesangial matrix area (p<0.00001 in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472.

  7. Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria

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    Mitra Basiratnia

    2012-01-01

    Full Text Available Diabetes mellitus (DM is now considered as the major cause of end-stage kidney failure, and hypertension (HTN is one of the main determinants of progression of renal disease. The aim of this study was to assess the role of blood pressure (BP by ambulatory blood pressure monitoring (ABPM in children and adolescents with type-1 DM and its correlation with micro-albuminuria (MA and diabetic control. Eighty-one patients with type-1 DM (mean age 13 ± 4 years, whose duration of DM was at least two years, were enrolled in this study. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN 11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN 30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were 33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4% had masked HTN, and 3.7% had white coat HTN. The pre-valence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. There was no correlation bet-ween HTN and both MA and HbA 1 c; also, no correlation was found between the duration of dia-betes and HbA 1 c. Moreover, no significant correlation was found between the duration of diabetes and MA (P = 0.080. Despite the high prevalence of abnormal BP profile among diabetic children, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have an impact on the progression to diabetic nephropathy, are recommended.

  8. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

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    van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin

    2016-09-01

    Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

  9. Documento de consenso para la detección y manejo de la enfermedad renal crónica

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    Alberto Martínez-Castelao

    2014-11-01

    Full Text Available La enfermedad renal crónica (ERC es un importante problema de salud pública que puede afectar en sus diferentes estadios a cerca del 10% de la población española y que supone una elevada morbimortalidad, así como un importante consumo de recursos al Sistema Nacional de Salud. Diez sociedades científicas involucradas en el manejo del paciente renal nos hemos puesto de acuerdo para hacer una puesta al día del anterior documento de consenso sobre ERC de 2007. El presente es la edición abreviada del documento general extenso, que puede ser consultado en las páginas Web de cada una de las sociedades firmantes. Contiene los siguientes aspectos: definición, epidemiología y factores de riesgo de la ERC; criterios de diagnóstico, evaluación y estadificación de la ERC, albuminuria y estimación del filtrado glomerular; concepto y factores de progresión; criterios de derivación a nefrología; seguimiento del paciente, actitudes y objetivos por especialidad; prevención de la nefrotoxicidad; detección del daño cardiovascular; actitudes, estilo de vida y tratamiento: manejo de la hipertensión arterial, dislipidemia, hiperglucemia, tabaquismo, obesidad, hiperuricemia, anemia, alteraciones del metabolismo mineral y óseo; seguimiento coordinado por atención primaria-otras especialidades-nefrología; manejo del paciente en tratamiento renal sustitutivo, hemodiálisis, diálisis peritoneal y trasplante renal; tratamiento paliativo de la uremia terminal. Esperamos que sirva de gran ayuda en el manejo multidisciplinar del paciente con ERC, a la vista de las recomendaciones más actualizadas.

  10. Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators - A pilot study

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    Alsuwaida Abdulkareem

    2010-01-01

    Full Text Available There are no available data about the prevalence of chronic kidney disease (CKD and its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and blood and urine samples were collected. Participants were categorized to their CKD stage according to their estimated Modification of Diet in Renal Disease (MDRD3-based, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation and the presence of albuminuria. The sample comprised 491 (49.9% were males adult Saudi nationals. The mean age was 37.4 ± 11.3 years. The over-all prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mel-litus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD. Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients.

  11. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  12. Potentiation of cadmium nephrotoxicity by acetaminophen

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    Bernard, A.M.; Russis, R. de; Ouled Amor, A.; Lauwerys, R.R.

    1988-10-01

    The possible interactions between acetaminophen and cadmium (Cd) on the kidney were investigated in female Sprague-Dawley rats. Acetaminophen was administered in the food at an average dose of 900 mg/kg and Cd in drinking water at the concentration of 200 ppm. The treatment with acetaminophen and Cd lasted 2 and 10 months, respectively. No interaction between Cd and acetaminophen was observed during the period of their concomitant administration: the increase in albuminuria caused by Cd and acetaminophen was additive, while the tubular impairment caused by acetaminophen (increased ..beta../sub 2/-microglobulinuria and decreased kidney concentrating ability) was not exacerbated by Cd. None of these treatments affected the glomerular filtration rate. Four months after the end of acetaminophen treatment, the renal changes had almost completely disappeared in the rats which had received the analgesic alone. Those continously exposed to Cd had developed slight tubular damage, as evidenced by an increased urinary excretion of ..beta../sub 2/-microglobulin and ..beta..-N-acetylglucosaminidase. By contrast, rats pretreated with acetaminophen for 2 months and exposed to Cd showed a marked increase in urinary excretion of albumin and ..beta../sub 2/-microglobulin, suggesting an interaction between both treatments. At the end of the study, only the interaction with ..beta../sub 2/-microglobulin excretion was still evident; that with the urinary excretion of ..beta..-N-acetylglucosaminidase and albumin having been masked by the chronic progessive nephrosis affecting most animals at that stage. As acetaminophen had no effect on the renal accumulation of Cd, it may be concluded that pretreatment with this analygesic at a dose causing slight tubular dysfunction renders rat kidney more sensitive to the nephrotoxic action of Cd. This observation may be of clinical relevance for population groups occupationally or environmentally exposed to Cd.

  13. Peripheral arterial disease among adult diabetic patients attending a large outpatient diabetic clinic at a national referral hospital in Uganda: a descriptive cross sectional study.

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    Raymond Mbayo Mwebaze

    Full Text Available BACKGROUND: Peripheral arterial disease (PAD is one of the recognised diabetic macro vascular complications. It is a marker of generalised systemic atherosclerosis and is closely associated with symptomatic coronary and cerebrovascular disease, hence significant morbidity and mortality. Among African adult diabetic populations, screening and diagnosis of PAD is frequently suboptimal. The aim of this study was to determine the prevalence and associated clinical factors of PAD in adult ambulatory diabetic patients attending the outpatient diabetic clinic of Mulago national referral and teaching hospital, Kampala Uganda. METHODS: In this descriptive cross sectional study, 146 ambulatory adult diabetic patients were studied. Information about their socio-demographic and clinical characteristics, fasting lipid profile status, blood pressure, glycated haemoglobin (HbA1c levels and presence of albuminuria was collected using a pre tested questionnaire. Measurement of ankle brachial index (ABI to assess for PAD, defined as a ratio less than 0.9 was performed using a portable 5-10 MHz Doppler device. Clinical factors associated with PAD were determined by comparing specific selected characteristics in patients with PAD and those without. RESULTS: The mean age/standard deviation of the study participants was 53.9/12.4 years with a male predominance (75, 51.4%. PAD was prevalent in 57 (39% study participants. Of these, 34 (59.6% had symptomatic PAD. The noted clinical factors associated with PAD in this study population were presence of symptoms of intermittent claudication and microalbuminuria. CONCLUSIONS: This study documents a high prevalence of PAD among adult ambulatory Ugandan diabetic patients. Aggressive screening for PAD using ABI measurement in adult diabetic patients should be emphasised in Uganda especially in the presence of symptoms of intermittent claudication and microalbuminuria.

  14. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice.

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    Gai, Zhibo; Gui, Ting; Hiller, Christian; Kullak-Ublick, Gerd A

    2016-01-29

    Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nuclear bile acid receptor in the prevention of diabetic nephropathy and obesity-induced renal damage. Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice that had undergone uninephrectomy, a model resembling the clinical situation of kidney donation by obese individuals. Mice fed a high-fat diet developed the core features of metabolic syndrome, with subsequent renal lipid accumulation and renal injury, including glomerulosclerosis, interstitial fibrosis, and albuminuria. The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was more prominent in the proximal tubules of 15 obese patients compared with 16 non-obese patients. In mice treated with the FXR agonist obeticholic acid, renal injury, renal lipid accumulation, apoptosis, and changes in lipid peroxidation were attenuated. Moreover, disturbed mitochondrial function was ameliorated and the mitochondrial respiratory chain recovered following obeticholic acid treatment. Culturing renal proximal tubular cells with free fatty acid and FXR agonists showed that FXR activation protected cells from free fatty acid-induced oxidative stress and endoplasmic reticulum stress, as denoted by a reduction in the level of reactive oxygen species staining and Grp78 immunostaining, respectively. Several genes involved in glutathione metabolism were induced by FXR activation in the remnant kidney, which was consistent with a decreased glutathione disulfide/glutathione ratio. In summary, FXR activation maintains endogenous glutathione homeostasis and protects the kidney in uninephrectomized mice from obesity-induced injury.

  15. P2Y2 receptor deficiency aggravates chronic kidney disease progression

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    Sebastian Alexander Potthoff

    2013-09-01

    Full Text Available Purinergic signaling is involved in a variety of physiological states. P2 receptors are mainly activated by adenosine triphosphate (ATP. Activation of specific P2Y receptor subtypes might influence progression of kidney disease. To investigate the in vivo effect of a particular P2 receptor subtype on chronic kidney disease progression, subtotal nephrectomy was performed on wild type (WT and P2Y2 receptor knockout (KO mice.During the observational period of 56 ± 2 days, survival of KO mice was inferior compared to WT mice after SNX. Subtotal nephrectomy reduced creatinine clearance in both groups of mice, but the decrease was significantly more pronounced in KO compared to WT mice (53.9±7.7 vs. 84.3±8.7µl/min at day 56. The KO mice also sustained a greater increase in systolic blood pressure after SNX compared to WT mice (177±2 vs. 156±7 mmHg and a 2.5-fold increase in albuminuria compared to WT. In addition, WT kidneys showed a significant increase in remnant kidney mass 56 days after SNX, but significant attenuation of hypertrophy in KO mice was observed. In line with the observed hypertrophy in WT SNX mice, a significant dose-dependent increase in DNA synthesis, a marker of proliferation, was present in cultured WT glomerular epithelial cells upon ATP stimulation. Markers for tissue damage (TGF-β1, PAI-1 and proinflammatory target genes (MCP1 were significantly upregulated in KO mice after SNX compared to WT SNX mice. In summary, deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice. Higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease.

  16. Target values of cardiovascular risk factors are not associated with all-cause mortality in patients with type 2 diabetes mellitus.

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    Antonio Pacilli

    Full Text Available To investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus.Two cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810 and the Foggia Mortality Study (n=929, were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient.In the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively, 161 (19.9% and 220 (23.7% patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively. When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004. This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852.In a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.

  17. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

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    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  18. Delayed mTOR inhibition with low dose of everolimus reduces TGFβ expression, attenuates proteinuria and renal damage in the renal mass reduction model.

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    Melania Kurdián

    Full Text Available BACKGROUND: The immunosuppressive mammalian target of rapamycin (mTOR inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. METHODS: This study evaluated the effects of everolimus (0.3 mg/k/day introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. RESULTS: Everolimus treated group (EveG showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial da