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Sample records for albuminuria

  1. 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-

  2. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    2010-01-01

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  3. 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

  4. 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

  5. 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

  6. Albuminuria : Is it Time to Screen the General Population?

    NARCIS (Netherlands)

    Crews, Deidra C.; Boulware, L. Ebony; Gansevoort, Ron T.; Jaar, Bernard G.

    2011-01-01

    Albuminuria has been associated with increased risk of multiple adverse outcomes, including ESRD, acute kidney injury, cardiovascular disease, and death. Some clinicians advocate for population-based screening of this condition, as a means of identifying individuals at high risk for morbidity and mo

  7. Podocyte Injury and Albuminuria in Experimental Hyperuricemic Model Rats

    Science.gov (United States)

    Asakawa, Shinichiro; Morimoto, Chikayuki; Shiraishi, Takeshi; Nakamura, Takashi; Tamura, Yoshifuru; Kumagai, Takanori; Hosoyamada, Makoto

    2017-01-01

    Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries. Notably, hyperuricemic rats showed significant albuminuria, and the podocyte injury marker, desmin, was upregulated in the glomeruli. Conversely, podocin, the key component of podocyte slit diaphragm, was downregulated. Structural analysis using transmission electron microscopy confirmed podocyte injury in this model. We found that urinary 8-hydroxy-2′-deoxyguanosine levels were significantly increased and correlated with albuminuria and podocytopathy. Interestingly, although the superoxide dismutase mimetic, tempol, ameliorated the vascular changes and the hypertension, it failed to reduce albuminuria, suggesting that vascular remodeling and podocyte injury in this model are mediated through different mechanisms. In conclusion, vasculopathy and podocytopathy may distinctly contribute to the kidney injury in a hyperuricemic state. PMID:28337250

  8. Diabetes mellitus, hypertension and albuminuria in rural Zambia

    DEFF Research Database (Denmark)

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

    2013-01-01

    . 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. Central obesity and albuminuria: both cross-sectional and longitudinal studies in Chinese.

    Directory of Open Access Journals (Sweden)

    Wen-Yuan Lin

    Full Text Available BACKGROUND: Albuminuria is recognized as a marker of vascular dysfunction. Central obesity increases the risk of cardiovascular disease. Little is known about the association between albuminuria and central obesity in Chinese. We aimed to assess the association between central obesity and prevalence and incidence of albuminuria in a middle-aged population-based cohort study. METHODS: This is a cross-sectional and longitudinal cohort study. A total of 2350 subjects aged ≥ 40 years were recruited in 2004 in Taiwan for cross-sectional analysis. Longitudinal analysis included 1432 baseline normoalbuminuria subjects with a mean 2.8 years follow-up, 67 of whom exhibited incident albuminuria. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g creatinine. Multiple logistic regression analyses were used to evaluate the relationship between central obesity and prevalence and incidence of albuminuria after adjustment for age, gender, body mass index, blood pressure, renal function, glucose, high sensitivity c-reactive protein, smoking, betel nut chewing, alcohol drinking, and physical activity. RESULTS: At baseline, albuminuria is significantly associated with central obesity. The adjusted odds ratio of having albuminuria among subjects with central obesity was 1.73(95% confidence interval (CI: 1.04-2.85, compared to the subjects without central obesity. In multivariable models, participants with central obesity at baseline had a 112% increase in risk of incident albuminuria (adjusted incidence rate ratio (95% CI: 2.12(1.01-4.44 compared with participants with non-central obesity. CONCLUSIONS: Abdominal adiposity was independently associated with increased prevalence and incidence of albuminuria in Chinese. The mechanisms linking adiposity and albuminuria need to be addressed.

  10. Smoking is related to albuminuria and abnormal renal function in nondiabetic persons

    NARCIS (Netherlands)

    Pinto-Sietsma, SJ; Mulder, J; Janssen, WMT; Hillege, HL; de Zeeuw, D; de Jong, PE

    2000-01-01

    Background: smoking induces albuminuria and accelerates progression to renal failure in persons with diabetes, but little is known about the relation between smoking and renal function in nondiabetic persons. Objective: To investigate whether smoking is related to albuminuria and abnormal renal func

  11. 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

  12. 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...

  13. 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

  14. 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

    data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes....... CONCLUSIONS: Increasing the number of urine collections per study visit and the number of visits over time does not change the average drug effect estimate but markedly increases the precision, thereby enhancing statistical power. Thus, clinical trial designs in diabetic nephropathy using albuminuria......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...

  15. 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.

  16. 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.

  17. Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, Peter; Tarnow, Lise; Rossing, Peter

    2004-01-01

    BACKGROUND: The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR...... risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01. CONCLUSION: Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression...... in diabetic nephropathy and a substantially improved survival....

  18. 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.

  19. The Selective Vitamin D Receptor Activator for Albuminuria Lowering (VITAL) Study : Study Design and Baseline Characteristics

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; Agarwal, R.; Coyne, D. W.; Parving, H. -H.; Ritz, E.; Remuzzi, G.; Audhya, P.; Amdahl, M. J.; Andress, D. L.; de Zeeuw, D.

    2009-01-01

    Background: Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains hig

  20. 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.......27). CONCLUSION: SAP treatment reduced UACR in a randomized controlled trial in type 1 diabetes patients with a history of albuminuria on stable RAS-inhibition. Significance was reached after adjustment. SAP treatment reduced HbA1c and glucose variability (calculated as SD)....

  1. 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

    . 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......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 fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A post hoc analysis...

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study

    OpenAIRE

    McMahon, Gearoid M.; Hwang, Shih-Jen; Rikki M Tanner; Jacques, Paul F.; Selhub, Jacob; Muntner, Paul; Fox, Caroline S.

    2015-01-01

    Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were ...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Oral supplementation with cholecalciferol 800 IU ameliorates albuminuria in Chinese type 2 diabetic patients with nephropathy.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available BACKGROUND: Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria. METHODS: Two studies were performed in which 25-OH vitamin D(3 (25(OHD(3 concentrations were determined by electrochemiluminescence immunoassay: 1 a cross-sectional study of patients with type 2 diabetes mellitus (T2DM (n = 481 and healthy controls (n = 78; and 2 a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22, and a control group (n = 24. RESULTS: 1 Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OHD(3 concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OHD(3 levels were independently correlated with microalbuminuria. 2 Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OHD(3 levels. CONCLUSIONS: Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.

  8. Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study.

    Science.gov (United States)

    Bakris, G L; Toto, R D; McCullough, P A; Rocha, R; Purkayastha, D; Davis, P

    2008-06-01

    Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

  9. Loss of the endothelial glycocalyx links albuminuria and vascular dysfunction.

    Science.gov (United States)

    Salmon, Andrew H J; Ferguson, Joanne K; Burford, James L; Gevorgyan, Haykanush; Nakano, Daisuke; Harper, Steven J; Bates, David O; Peti-Peterdi, Janos

    2012-08-01

    Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MWF) rats as a model of spontaneous albuminuric CKD, multiphoton fluorescence imaging and single-vessel physiology measurements revealed that old MWF rats exhibited widespread loss of the endothelial surface layer in parallel with defects in microvascular permeability to both water and albumin, in both continuous mesenteric microvessels and fenestrated glomerular microvessels. In contrast to young MWF rats, enzymatic disruption of the endothelial surface layer in old MWF rats resulted in neither additional loss of the layer nor additional changes in permeability. Intravenous injection of wheat germ agglutinin lectin and its adsorption onto the endothelial surface layer significantly improved glomerular albumin permeability. Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease.

  10. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease

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    Nan Wu

    2014-01-01

    Full Text Available Aims. Left ventricular hypertrophy (LVH and albuminuria are both markers for cardiovascular diseases (CVDs in patients with type 2 diabetes mellitus (T2DM. We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; P<0.001. Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; P<0.001, age (P<0.001, systolic blood pressure (P=0.0578, and the use of ACEI/ARB drug (P<0.001 were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464 and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993 compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%, followed by eccentric hypertrophy (21.0%. Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD.

  11. Albuminuria is an independent risk factor of T4 elevation in chronic kidney disease

    Science.gov (United States)

    Du, Xin; Pan, Binbin; Li, Wenwen; Zou, Yonghua; Hua, Xi; Huang, Wenjuan; Wan, Xin; Cao, Changchun

    2017-01-01

    This study was to explore the association between thyroid dysfunction and albuminuria. 581 cases with chronic kidney disease (CKD) were included in this study. The clinical characteristics consisted of sex, age, serum creatinine, urinary albumin-to-creatinine ratio (ACR), thyroid function were recorded. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI four-level race equation. Prevalence of different thyroid diseases was calculated by chi-square test. Levels of thyroid hormone were compared among different albuminuria groups by Kruskal-Wallis test. Spearman’s correlation was used to assess the association between albuminuria and thyroid hormone. Our study showed that total T4 and free T4 were significantly different among ACR 300 mg/g (P hs-CRP, smoking status, systolic blood pressure, diabetes mellitus, medication use for diabetes mellitus, eGFR, LDL-cholesterol, triglycerides, hypertension, and medication use for hypercholesterinemia. In conclusion, T4 was positively correlated with albuminuria, and it was completely not consistent with our anticipation. Further study is needed to elucidate the causation association between albuminuria and T4. PMID:28117377

  12. Association between Salt Intake and Albuminuria in Normotensive and Hypertensive Individuals

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    Arsalan Khaledifar

    2013-01-01

    Full Text Available Background. There is a little published data regarding the association between salt intake and albuminuria as an important alarm for progression of cardiovascular and renal dysfunction. We aimed to assess this relationship to emphasize the major role of restricting salt intake to minimize albuminuria and prevent these life-threatening events. Methods. The study population comprised 820 individuals. Participants were assigned to groups as follows: normal albuminuria, slight albuminuria, and clinical albuminuria. Daily salt intake was assessed on the basis of 24-hour urinary sodium excretion, since urinary sodium excretion largely equals sodium intake. Results. In normotensive participants, the mean level of urine albumin was higher in those who had higher amounts of salt intake with a significantly upward trend (the mean urinary albumin level in low-salt-diet group, in medium-salt-intake group, and in high-salt-intake group was 42.70±36.42, 46.89±38.91, and 53.38±48.23, resp., (P=0.017. There was a significant positive correlation between 24-hour urinary sodium secretion and the level of urine albumin (beta = 0.130, P<0.001. The amount of salt intake was significantly associated with urine albumin concentration (beta = 3.969, SE = 1.671, P=0.018. Conclusion. High salt intake was shown to be associated with higher level of microalbuminuria even adjusted for potential underlying risk factors.

  13. Liraglutide effects on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Persson, Frederik; Rosenlund, Signe;

    2017-01-01

    -regional pro-atrial natriuretic peptide (MR-proANP); and 5) Copeptin, in type 2 diabetes patients with albuminuria. In a randomised, double-blind, placebo-controlled, cross-over trial we enrolled patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio (UACR) > 30 mg....../g) and estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m(2) . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in random order. Primary endpoint was change in albuminuria; this is a prespecified sub-study. Thirty-two patients were randomised, 27 completed the study. TNF...

  14. 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

    Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further...... parameters returned to pretreatment levels. In conclusion, atrasentan reduced albuminuria and improved BP and lipid spectrum with manageable fluid overload-related adverse events in patients with type 2 diabetic nephropathy receiving RAS inhibitors....... reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double...

  15. ABNORMAL PLASMA NORADRENALINE RESPONSE AND EXERCISE INDUCED ALBUMINURIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

    NARCIS (Netherlands)

    HOOGENBERG, K; DULLAART, RPF

    1992-01-01

    Submaximal exercise provokes an abnormal elevation in albuminuria in type 1 (insulin-dependent) diabetes mellitus. Plasma catecholamines might be involved in this phenomenon by a renal vasoconstrictive effect. Twelve healthy subjects (Controls: albuminuria It is concluded that the exercise-induced p

  16. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients with left ventricular hypertrophy and diabetes

    DEFF Research Database (Denmark)

    Ibsen, H.; Olsen, M.H.; Wachtell, K.

    2008-01-01

    of development of diabetic nephropathy. In the LIFE-diabetes subgroup we found that reduction in albuminuria was more pronounced in losartan-based as compared with atenolol-based treatment. The benefit in favor of losartan was partly related to its major influence on albuminuria. Individuals with the highest......In type 2 diabetes the degree of albuminuria is strongly related to progression of diabetic renal disease, as well as to the risk for cardiovascular complications. If normoalbuminuria is maintained, the risk of diabetic nephropathy is very low. In individuals with microalbuminuria, the rate......, well below traditional levels for microalbuminuria, predict cardiovascular morbidity and mortality. Reduction in albuminuria during treatment translates to reduction in cardiovascular events. Monitoring of albuminuria should be an integrated part of management of hypertension in diabetic as well...

  17. 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

  18. 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

  19. 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

  20. 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...

  1. 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

  2. Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes

    DEFF Research Database (Denmark)

    Webb, D R; Zaccardi, F; Davies, M J

    2016-01-01

    BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria five years after a diagnosis of screen-detected diabetes within the ADDITION-E...

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

    DEFF Research Database (Denmark)

    Rasmussen, Jon Bjarke Jarløv; Nordin, Lovisa S.; Thomsen, Jakup Andreas

    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 charac...

  4. Albuminuria : all you need to predict outcomes in chronic kidney disease?

    NARCIS (Netherlands)

    Gansevoort, Ron T.; Nauta, Ferdau L.; Bakker, Stephan J. L.

    2010-01-01

    Purpose of review Screening for chronic kidney disease frequently starts with assessment of estimated glomerular filtration rate (eGFR). In current approaches, further evaluation will only include measurement of albuminuria in case of eGFR less than 60 ml/min/1.73m(2). We will review whether this sc

  5. DIETARTY EDUCATOIN IN TYPE 1 DIABETES EDUCATION (DAFNE AND ALBUMINURIA CHANGE: KUWAIT’S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Ebaa Al Ozairi

    2012-06-01

    In conclusion, this study shows significantly improvement in albuminurea with sustained improvement in HbA1c through better carbohydrate skills. DAFNE course should prove cost effective with sustained glycemic profile and improvement of albuminuria and should become more widely available.

  6. 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

  7. A comparison of podocyturia, albuminuria and nephrinuria in predicting the development of preeclampsia: a prospective study.

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    Belinda Jim

    Full Text Available Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia, or the podocyte specific proteinuria nephrin in the urine (nephrinuria, as well as the more easily measured urinary albumin (albuminuria, have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk and studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 15-38 weeks of gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia, nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria were 57% and 58%, respectively. Also, abnormal nephrinuria (69% and podocyturia (38% were detected in low risk women who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however, may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be considered.

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

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    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

  9. Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease

    DEFF Research Database (Denmark)

    Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe;

    2016-01-01

    clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions...... used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from......Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four...

  10. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

    OpenAIRE

    Gopinath, S.; B Amirtha Ganesh; Manoj, K; Rubiya,

    2012-01-01

    Introduction: Two-year follow-up of patients with diabetes mellitus (DM) nephropathy shows albuminuria reversal following angiotensin converting enzyme (ACE) inhibitors. Aim: To study about a clinical profile of 2-year follow-up of patients with DM nephropathy showing albuminuria reversal following ACE inhibitors. Materials and Methods: Twenty patients were taken up for study with duly informed consent and suggested for glycemic profile with HbA1C. Baseline renal function, urine microscopy, a...

  11. 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...

  12. The selective vitamin D receptor activator for albuminuria lowering (VITAL) study: study design and baseline characteristics

    DEFF Research Database (Denmark)

    Lambers Heerspink, H J; Agarwal, R; Coyne, D W

    2009-01-01

    BACKGROUND: Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains....... Inclusion criteria include: a diagnosis of type 2 diabetes, urinary albumin/creatinine ratio (UACR) between 100-3,000 mg/g, estimated glomerular filtration rate (eGFR) between 15-90 ml/min/1.73 m(2), serum calcium ... paricalcitol persistently reduces albuminuria in diabetic subjects already receiving angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) therapy. METHODS: Randomization in this double-blind trial is equal allocation to paricalcitol 1 micro/day, 2 microg/day, or placebo...

  13. 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...

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

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    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

  15. Low birth weight and risk of albuminuria in living kidney donors

    Science.gov (United States)

    Berglund, D; MacDonald, D; Jackson, S; Spong, R; Issa, N; Kukla, A; Reule, S; Weber, M; Matas, AJ; Ibrahim, HN

    2015-01-01

    Low birth weight is linked to hypertension, chronic kidney disease and even end stage renal disease. We hypothesized that living kidney donors born with lower birth weight may be at increased risk of hypertension, albuminuria or reduced GFR beyond what is typical following uninephrectomy. 257 living kidney donors who donated at the University of Minnesota between 1967 and 2005 underwent iohexol GFR and urinary albumin excretion measurements. Predictors of iohexol GFR <60 ml/min/1.73m2, albuminuria and hypertension were examined using logistic regression. Predictors examined include age at GFR measurement, time since donation, BMI, gender, serum creatinine level (at donation and GFR measurement), systolic and diastolic blood pressure, race, and birth weight. The latter was obtained through self-report and verified through birth certificates and family members. Older age, higher BMI, and time from donation were associated with reduced GFR. Older age and higher BMI were also associated with hypertension. Birth weight was not associated with GFR <60 ml/min/1.73m2: OR=0.70, 95% CI (0.28, 1.74, p=0.45) or hypertension: OR=0.92, 95% CI (0.46, 1.84), p=0.82 but was associated with albuminuria: OR=0.37, 95% CI (0.15, 0.92), p=0.03. This data further strengthens the link between low birth weight and potential adverse renal outcomes. PMID:24547690

  16. 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.

  17. Risks of Decreased Renal Function and Increased Albuminuria for Glycemic Status and Metabolic Syndrome Components: Taichung Community Health Study

    Directory of Open Access Journals (Sweden)

    Cheng-Chieh Lin

    2014-01-01

    Full Text Available Background. The objective of this study was to assess the association of glycemic status and decreased renal function as determined by estimated glomerular filtration rate (eGFR and albuminuria in an adult Taiwanese metropolitan population. Methods. We did a cross-sectional survey in a representative sample of 2,350 Taiwanese adults aged 40 years and over living in a metropolitan city in Taiwan from 2004 to 2005. Glycemic status was classified as normal glycemia, hyperglycemia, and type 2 diabetes (T2D. Renal function was assessed with eGFR using modified Modification of Diet in Renal Disease Study equation for Chinese. Albuminuria was determined by the urinary albumin-creatinine ratio. Decreased renal function was defined as eGFR 30 mg g−1 creatinine. Results. 593 (25.23% had hyperglycemia and 287 (12.21% had T2D. As glycemia level increased, the prevalence of albuminuria and decreased eGFR increased. After adjustment, T2D was associated with an OR of 2.93 (95% CI: 2.11–4.07 for albuminuria, and an OR of 2.05 (95% CI: 1.18–3.58 for decreased eGFR. Conclusions. In a representative sample from a metropolitan city in Taiwan, T2D was associated with albuminuria and decreased eGFR.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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; Leach, I. Mateo; 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.

    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-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

  20. 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.

  1. Increased incidence of kidney diseases in general practice after a nationwide albuminuria self-test program

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    Verheij Robert A

    2011-08-01

    Full Text Available Abstract Background To study the influence of a nationwide albuminuria self-test program on the number of GP contacts for urinary complaints and/or kidney diseases and the number of newly diagnosed patients with kidney diseases by the GP. Methods Data were used from the Netherlands Information Network of General Practice (LINH, including a representative sample of general practices with a dynamic population of approximately 300.000 listed patients. Morbidity data were retrieved from electronic medical records, kept in a representative sample of general practices. The incidence of kidney diseases and urinary complaints before and after the albuminuria self-test program was compared with logistic regression analyses. Results Data were used from 139 general practices, including 444,220 registered patients. The number of GP consultations for kidney diseases and urinary complaints was increased in the year after the albuminuria self-test program and particularly shortly after the start of the program. Compared with the period before the self-test program, more patients have been diagnosed by the GP with symptoms/complaints of kidney disease and urinary diseases (OR = 1.7 (CI 1.4 - 2.0 and OR = 2.1 (CI 1.9 - 2.3, respectively. The odds on an abnormal urine-test in the period after the self-test program was three times higher than the year before (OR = 3.0 (CI 2.4 - 3.6. The effect of the self-test program on newly diagnosed patients with an abnormal urine test was modified by both the presence of the risk factors hypertension and diabetes mellitus. For this diagnosis the highest OR was found in patients without both conditions (OR = 4.2 (CI 3.3 - 5.4. Conclusions A nationwide albuminuria self-test program resulted in an increasing number of newly diagnosed kidney complaints and diseases the year after the program. The highest risks were found in patients without risk factors for kidney diseases.

  2. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Agarwal, Rajiv; Amdahl, Michael;

    2010-01-01

    Despite treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, patients with diabetes have increased risk of progressive renal failure that correlates with albuminuria. We aimed to assess whether paricalcitol could be used to reduce albuminuria in patients with diabetic nephropathy....

  3. Is albuminuria screening and treatment optimal in patients with type 2 diabetes in primary care? Observational data of the GIANTT cohort

    NARCIS (Netherlands)

    Hellemons, M.E.; Denig, P.; Voorham, J.; Heerspink, H.J.L.; de Zeeuw, Dick

    2013-01-01

    Failure of diagnosing and treatment of albuminuria play a role in morbidity and mortality in type 2 diabetes (T2DM). We evaluated guideline adherence and factors associated with albuminuria screening and treatment in T2DM patients in primary care. Guidelines recommend annual measurement of albuminur

  4. 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.

  5. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

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    S Gopinath

    2012-01-01

    Full Text Available Introduction: Two-year follow-up of patients with diabetes mellitus (DM nephropathy shows albuminuria reversal following angiotensin converting enzyme (ACE inhibitors. Aim: To study about a clinical profile of 2-year follow-up of patients with DM nephropathy showing albuminuria reversal following ACE inhibitors. Materials and Methods: Twenty patients were taken up for study with duly informed consent and suggested for glycemic profile with HbA1C. Baseline renal function, urine microscopy, albuminuria, and other microvascular complications such as neuropathy and retinopathy. These patients were followed up for a period of 2 years with every month follow-up and monthly dose titration of ACE inhibitors, enalapril (Quote: Dr. M. K. Mani, to a maximum tolerable dose and checked after 1 week for raise in creatinine and potassium. Inclusion Criteria: Twenty patients, who have attended a secondary level diabetic clinic with diabetic nephropathy and are on regular follow-up for 2 years, were selected. Exclusion Criteria: Sick patients requiring parenteral feeds, IV antibiotics, co-morbid conditions such as autonomic gastroparesis and diabetic foot infections, type 1 diabetes and other known kidney disease, chronic kidney disease on dialysis are excluded from the study. Expected Result: Reversal of albuminuria. Conclusion: Enalapril is a safe, cheaper ACE inhibitors and the good dose titration coupled with early screening for DM nephropathy really help in halting the progression of chronic kidney disease from DM nephropathy.

  6. Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

    NARCIS (Netherlands)

    Nitsch, D.; Grams, M.; Sang, Y.; Black, C.; Cirillo, M.; Djurdjev, O.; Iseki, K.; Jassal, S.K.; Kimm, H.; Kronenberg, F.; Oien, C.M.; Levey, A.S.; Levin, A.; Woodward, M.; Hemmelgarn, B.R.; Wetzels, J.F.

    2013-01-01

    OBJECTIVE: To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. DESIGN: Random effects meta-analysis using pooled individual participant data. SETTI

  7. Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is increased in Type 1 diabetic patients with albuminuria

    NARCIS (Netherlands)

    Leurs, PB; van Oerle, R; Hamulyak, K; Wolffenbuttel, BHR

    2003-01-01

    Aims To study heparin-stimulated TFPI release in relation to complications in Type 1 diabetic patients. Subjects and methods Nineteen uncomplicated Type 1 diabetic patients (group I) were compared with 18 patients with retinopathy (group II), and nine patients with retinopathy and albuminuria (group

  8. 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,

  9. 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

  10. Is a reduction in albuminuria associated with renal and cardiovascular protection? : A post-hoc analysis of the ALTITUDE trial

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J; Ninomiya, Toshiharu; Persson, Frederik; Brenner, Barry M; Brunel, Patrick; Chaturvedi, Nish; Desai, Akshay S; Haffner, S M; Mcmurray, John J V; Solomon, Scott D; Pfeffer, Marc A; Parving, Hans-Henrik; de Zeeuw, Dick

    2015-01-01

    AIMS: In the ALTITUDE trial, direct renin inhibition with aliskiren on top of ACEi_or_ARB therapy decreased albuminuria by 14% while this did not lead to cardiorenal protection. Prior studies have demonstrated that the renoprotective effect of single RAAS blockade is associated with approximately 30

  11. 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.

  12. Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

    Science.gov (United States)

    Uzu, Takashi; Araki, Shin-ichi; Kashiwagi, Atsunori; Haneda, Masakazu; Koya, Daisuke; Yokoyama, Hiroki; Kida, Yasuo; Ikebuchi, Motoyoshi; Nakamura, Takaaki; Nishimura, Masataka; Takahara, Noriko; Obata, Toshiyuki; Omichi, Nobuyuki; Sakamoto, Katsuhiko; Shingu, Ryosuke; Taki, Hideki; Nagai, Yoshio; Tokuda, Hiroaki; Kitada, Munehiro; Misawa, Miwa; Nishiyama, Akira; Kobori, Hiroyuki; Maegawa, Hiroshi

    2016-01-01

    Background In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity. Methods We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria. Results Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients. Conclusion DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen. PMID:28033332

  13. Evaluation of Urinary Indices for Albuminuria and Proteinuria in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Dennis Sung Chul Hong

    2016-04-01

    Full Text Available Background/Aims: Either protein-to-creatinine ratio (PCR or albumin-to-creatinine ratio (ACR can be adopted for estimation of proteinuria in patients with chronic kidney disease (CKD. Estimated protein excretion rate (ePER and estimated albumin excretion rate (eAER may be superior to ACR and PCR. Reports show that urine albumin-to-protein ratio (APR may be useful in detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP. Methods: Both 24-h urine and spot urine were collected from 77 stable CKD patients for measurement of albumin, protein, and creatinine, and PEP. Based on MDRD and CKD-EPI equations, ePERMDRD, ePERCKD-EPI, eAERMDRD and eAERCKD-EPI were calculated to estimate daily proteinuria and albuminuria. Glomerular CKD was defined by clinical and/or pathological evidence. Results: ACR correlated significantly with PCR. However, microalbuminuria was present in patients without pathologic proteinuria. Twenty-four-hour urine albumin correlated better with eAERMDRD and eAERCKD-EPI than ACR, and 24-h urine protein correlated better with ePERMDRD and ePERCKD-EPI than PCR. APR significantly but not well correlated with the albumin fraction in urine PEP. The albumin fraction obtained from urine PEP was significantly higher in patients with glomerulopathy than those with non-glomerular CKD, whereas there were no differences in APR between groups. In contrast with APR, the albumin fraction in urine PEP was independently associated with glomerular CKD. Conclusions: Both PCR and ACR are useful in evaluation of proteinuria. In quantifying daily proteinuria and albuminuria, ePER and eAER are superior to PCR and ACR, respectively. Compared with APR, urine PEP is more useful in diagnosing glomerular proteinuria.

  14. High rates of albuminuria but not of low eGFR in Urban Indigenous Australians: the DRUID Study

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    Zimmet Paul Z

    2011-05-01

    Full Text Available Abstract Background Indigenous Australians have an incidence of end stage kidney disease 8-10 times higher than non-Indigenous Australians. The majority of research studies concerning Indigenous Australians have been performed in rural or remote regions, whilst the majority of Indigenous Australians actually live in urban settings. We studied prevalence and factors associated with markers of kidney disease in an urban Indigenous Australian cohort, and compared results with those for the general Australian population. Methods 860 Indigenous adult participants of the Darwin Region Urban Indigenous Diabetes (DRUID Study were assessed for albuminuria (urine albumin-creatinine ratio≥2.5 mg/mmol males, ≥3.5 mg/mmol females and low eGFR (estimated glomular filtration rate 2. Associations between risk factors and kidney disease markers were explored. Comparison was made with the AusDiab cohort (n = 8,936 aged 25-64 years, representative of the general Australian adult population. Results A high prevalence of albuminuria (14.8% was found in DRUID, whilst prevalence of low eGFR was 2.4%. Older age, higher HbA1c, hypertension, higher C-reactive protein and current smoking were independently associated with albuminuria on multiple regression. Low eGFR was independently associated with older age, hypertension, albuminuria and higher triglycerides. Compared to AusDiab participants, DRUID participants had a 3-fold higher adjusted risk of albuminuria but not of low eGFR. Conclusions Given the significant excess of ESKD observed in Indigenous versus non-Indigenous Australians, these findings could suggest either: albuminuria may be a better prognostic marker of kidney disease than low eGFR; that eGFR equations may be inaccurate in the Indigenous population; a less marked differential between Indigenous and non-Indigenous Australians for ESKD rates in urban compared to remote regions; or that differences in the pathophysiology of chronic kidney disease exist

  15. Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial.

    Science.gov (United States)

    Keyzer, Charlotte A; van Breda, G Fenna; Vervloet, Marc G; de Jong, Maarten A; Laverman, Gozewijn D; Hemmelder, Marc H; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Bakker, Stephan J L; Navis, Gerjan; de Borst, Martin H

    2017-04-01

    Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BPsodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (Psodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.

  16. Scoring System Development and Added Value of Albuminuria to Estimate Carotid Intima-media Thickness (CIMT in Type 2 Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Indra Wijaya

    2017-02-01

    Full Text Available Aim: to develop a scoring system and measure the diagnostic added value of albuminuria to estimate CIMT. Methods: cross-sectional study was done in Endocrine Outpatient Clinic Cipto Mangunkusumo Hospital between March-May 2012 in T2DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking. Bivariate analysis and multivariate (logistic regression analysis was done, followed by developing the scoring system. Results: from 71 subjects, there were 67.6% with increased CIMT and 73.3% with albuminuria. From 48 subjects with increased CIMT, 87.5% had albuminuria. Albuminuria measurement had high sensitivity (87.5%. Adding albuminuria measurement will increase the AUC as 2.3%. Estimation score for duration of DM, hypertension, dyslipidemia were as follows 1, 2, 1 respectively. Probability score of increased CIMT for score 2 was as follows 15%, 57%, and 90%. Conclusion: albuminuria measurement increase the diagnostic value of CIMT. Scoring system can be used as a screening tool to estimate the increased of CIMT in type 2 DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking.

  17. Association of Renal Resistive Index, Renal Pulsatility Index, Systemic Hypertension, and Albuminuria with Survival in Dogs with Pituitary-Dependent Hyperadrenocorticism

    Directory of Open Access Journals (Sweden)

    Hung-Yin Chen

    2016-01-01

    Full Text Available An increased renal resistive index (RI and albuminuria are markers of target organ damage secondary to systemic hypertension. This study evaluated associations between systemic blood pressure (SBP, renal RI, pulsatility index (PI, and albuminuria in dogs with pituitary-dependent hyperadrenocorticism (PDH. Predictors of overall mortality were investigated. Twenty client-owned dogs with PDH and 20 clinically healthy client-owned dogs as matched controls were included. Incidence rates of systemic hypertension (SBP ≥ 160 mmHg, albuminuria, and increased renal RI (≥ 0.70 and PI (≥ 1.45 in the control group were 5%, 0%, 5%, and 0%, respectively, compared to 35%, 40%, 50%, and 35%, respectively, in the PDH group (P=0.001, P<0.001, P<0.001, and P=0.001, resp.. No association between systemic hypertension, renal RI, renal PI, and albuminuria was observed. PDH was the only predictor of albuminuria and increased renal RI. Survival was not affected by increased renal PI, systemic hypertension, or albuminuria. Increased renal RI (≥ 0.70 was the only predictor of overall mortality in dogs with PDH.

  18. Effects of combined lipoic acid and pyridoxine on albuminuria, advanced glycation end-products, and blood pressure in diabetic nephropathy.

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    Noori, Nazanin; Tabibi, Hadi; Hosseinpanah, Farhad; Hedayati, Mehdi; Nafar, Mohsen

    2013-01-01

    This study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycation end-products, nitric oxide (NO), and endothelin-1 in patients with diabetic nephropathy. Thirty-four patients were randomly assigned to either a supplement group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, whereas the placebo group received corresponding placebos. Urinary albumin, serum malondialdehyde (MDA), and systolic blood pressure decreased significantly in the supplement group compared to the placebo group (p blood pressure. The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress, advanced glycation end-products, and systolic blood pressure. The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy.

  19. 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

  20. 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.

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

    Science.gov (United States)

    Nielen, Markus MJ; Schellevis, François G; Verheij, Robert A

    2009-01-01

    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. PMID:19818129

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

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    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.

  3. Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria

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    Jazbec, Anamarija; Tomic, Martina; Piljac, Ante; Jurisic Erzen, Dubravka; Novak, Branko; Kastelan, Snjezana; Lovrencic, Marijana Vucic; Brkljacic, Neva

    2015-01-01

    Aims. To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy. Methods. ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients. Results. Significant differences among ApN levels according to AER were found in both types of diabetes (F = 8.45, df = 2, P < 0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F = 12.7, df = 1, P < 0.001). The best model for ApN (R2 = 0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R2 = 0.2882) it included ppPG, LDL, and UA. Conclusion. ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes. PMID:26089882

  4. Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria

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    Spomenka Ljubic

    2015-01-01

    Full Text Available Aims. To investigate the behaviour of adiponectin (ApN in patients with type 1 and type 2 diabetic nephropathy. Methods. ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER, and creatinine clearance (CrCl categories in 219 type 1 and type 2 diabetic patients. Results. Significant differences among ApN levels according to AER were found in both types of diabetes (F=8.45, df=2, P<0.001. With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F=12.7, df=1, P<0.001. The best model for ApN (R2=0.9002 obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R2=0.2882 it included ppPG, LDL, and UA. Conclusion. ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes.

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

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    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.

  6. Exercise-induced albuminuria vs circadian variations in blood pressure in type 1 diabetes

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    Tadida Meli, Isabelle Hota; Tankeu, Aurel T; Dehayem, Mesmin Y; Chelo, David; Noubiap, Jean Jacques N; Sobngwi, Eugene

    2017-01-01

    AIM To investigated the relationship between exercise-induced ambulatory blood pressure measurement (ABPM) abnormalities in type 1 diabetes mellitus (T1DM) adolescents. METHODS We conducted a case-control at the National Obesity Center of the Yaoundé Central Hospital, Cameroon. We compared 24 h ABPM and urinary albumin-to-creatinine ratio (ACR) at rest and after a standardized treadmill exercise between 20 Cameroonian T1DM patients and 20 matched controls. T1DM adolescents were aged 12-18 years, with diabetes for at least one year, without proteinuria, with normal office blood pressure (BP) and renal function according to the general reference population. Non-diabetic controls were adolescents of general population matched for sex, age and BMI. RESULTS Mean duration of diabetes was 4.2 ± 2.8 years. The mean 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively 116 ± 9 mmHg in the diabetic group vs 111 ± 8 mmHg in the non-diabetic (P = 0.06), and 69 ± 7 mm Hg vs 66 ± 5 mm Hg (P = 0.19). There was no difference in the diurnal pattern of BP in diabetes patients and non-diabetic controls (SBP: 118 ± 10 mmHg vs 114 ± 10 mmHg, P = 0.11; DBP: 71 ± 7 mmHg vs 68 ± 6 mmHg, P = 0.22). Nighttime BP was higher in the diabetic group with respect to SBP (112 ± 11 mmHg vs 106 ± 7 mmHg, P = 0.06) and to the mean arterial pressure (MAP) (89 ± 9 mmHg vs 81 ± 6 mmHg, P = 0.06). ACR at rest was similar in both groups (5.5 mg/g vs 5.5 mg/g, P = 0.74), but significantly higher in diabetes patients after exercise (10.5 mg/g vs 5.5 mg/g, P = 0.03). SBP was higher in patients having exercise-induced albuminuria (116 ± 10 mmHg vs 108 ± 10 mmHg, P = 0.09). CONCLUSION Exercise-induced albuminuria could be useful for early diagnosis of kidney damage in adolescents with T1DM.

  7. A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND.

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    Dov Shiffman

    Full Text Available Although albuminuria and subsequent advanced stage chronic kidney disease are common among patients with diabetes, the rate of increase in albuminuria varies among patients. Since genetic variants associated with estimated glomerular filtration rate (eGFR were identified in cross sectional studies, we asked whether these variants were also associated with rate of increase in albuminuria among patients with diabetes from ONTARGET and TRANSCEND-randomized controlled trials of ramipril, telmisartan, both, or placebo. For 16 genetic variants associated with eGFR at a genome-wide level, we evaluated the association with annual rate of increase in albuminuria estimated from urine albumin:creatinine ratio (uACR. One of the variants (rs267734 was associated with rate of increase in albuminuria. The annual rate of increase in albuminuria among risk homozygotes (69% of the study population was 11.3% (95%CI; 7.5% to 15.3%, compared with 5.0% (95%CI; 3.3% to 6.8% for heterozygotes (27% of the population, and 1.7% (95%CI; -1.7% to 5.3% for non-risk homozygotes (4% of the population; P = 0.0015 for the difference between annual rates in the three genotype groups. These estimates were adjusted for age, sex, ethnicity, and principal component of genetic heterogeneity. Among patients without albuminuria at baseline (uACR<30 mg/g, each risk allele was associated with 50% increased risk of incident albuminuria (OR = 1.50; 95%CI 1.15 to 1.95; P = 0.003 after further adjustment for traditional risk factors including baseline uACR and eGFR. The rs267734 variant is in almost perfect linkage-disequilibrium (r2 = 0.94 with rs267738, a single nucleotide polymorphism encoding a glutamic acid to alanine change at position 115 of the ceramide synthase 2 (CERS2 encoded protein. However, it is unknown whether CERS2 function influences albuminuria. In conclusion, we found that rs267734 in CERS2 is associated with rate of increase in albuminuria among patients

  8. A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND.

    Science.gov (United States)

    Shiffman, Dov; Pare, Guillaume; Oberbauer, Rainer; Louie, Judy Z; Rowland, Charles M; Devlin, James J; Mann, Johannes F; McQueen, Matthew J

    2014-01-01

    Although albuminuria and subsequent advanced stage chronic kidney disease are common among patients with diabetes, the rate of increase in albuminuria varies among patients. Since genetic variants associated with estimated glomerular filtration rate (eGFR) were identified in cross sectional studies, we asked whether these variants were also associated with rate of increase in albuminuria among patients with diabetes from ONTARGET and TRANSCEND-randomized controlled trials of ramipril, telmisartan, both, or placebo. For 16 genetic variants associated with eGFR at a genome-wide level, we evaluated the association with annual rate of increase in albuminuria estimated from urine albumin:creatinine ratio (uACR). One of the variants (rs267734) was associated with rate of increase in albuminuria. The annual rate of increase in albuminuria among risk homozygotes (69% of the study population) was 11.3% (95%CI; 7.5% to 15.3%), compared with 5.0% (95%CI; 3.3% to 6.8%) for heterozygotes (27% of the population), and 1.7% (95%CI; -1.7% to 5.3%) for non-risk homozygotes (4% of the population); P = 0.0015 for the difference between annual rates in the three genotype groups. These estimates were adjusted for age, sex, ethnicity, and principal component of genetic heterogeneity. Among patients without albuminuria at baseline (uACR<30 mg/g), each risk allele was associated with 50% increased risk of incident albuminuria (OR = 1.50; 95%CI 1.15 to 1.95; P = 0.003) after further adjustment for traditional risk factors including baseline uACR and eGFR. The rs267734 variant is in almost perfect linkage-disequilibrium (r2 = 0.94) with rs267738, a single nucleotide polymorphism encoding a glutamic acid to alanine change at position 115 of the ceramide synthase 2 (CERS2) encoded protein. However, it is unknown whether CERS2 function influences albuminuria. In conclusion, we found that rs267734 in CERS2 is associated with rate of increase in albuminuria among patients with

  9. 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

  10. BlockingαVβ3 Integrin Ligand Occupancy Inhibits the Progression of Albuminuria in Diabetic Rats

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    Laura A. Maile

    2014-01-01

    Full Text Available This study determined if blocking ligand occupancy of the αVβ3 integrin could inhibit the pathophysiologic changes that occur in the early stages of diabetic nephropathy (DN. Diabetic rats were treated with either vehicle or a monoclonal antibody that binds the β3 subunit of the αVβ3 integrin. After 4 weeks of diabetes the urinary albumin to creatinine ratio (UACR increased in both diabetic animals that subsequently received vehicle and in the animals that subsequently received the anti-β3 antibody compared with control nondiabetic rats. After 8 weeks of treatment the UACR continued to rise in the vehicle-treated rats; however it returned to levels comparable to control nondiabetic rats in rats treated with the anti-β3 antibody. Treatment with the antibody prevented the increase of several profibrotic proteins that have been implicated in the development of DN. Diabetes was associated with an increase in phosphorylation of the β3 subunit in kidney homogenates from diabetic animals, but this was prevented by the antibody treatment. This study demonstrates that, when administered after establishment of early pathophysiologic changes in renal function, the anti-β3 antibody reversed the effects of diabetes normalizing albuminuria and profibrotic proteins in the kidney to the levels observed in nondiabetic control animals.

  11. 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.

  12. Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria.

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    Chen, Wei-Zhi; Hung, Cheng-Chieh; Wen, Yu-Wen; Ning, Hsiao-Chen; Gau, Bing-Ru; Huang, Yu-Yao

    2014-03-01

    This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of 60 mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10 mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC = 0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC = 0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR ( 8%, high-normal UACR/HbA1c 8% were 2.59 (p = 0.107), 6.15 (p = 0.001), and 16.96 (p 10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.

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

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    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.

  14. Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy.

    Science.gov (United States)

    Ju, Kyung Don; Shin, Eun Kyoung; Cho, Eun Jin; Yoon, Hyun Bae; Kim, Hyo Sang; Kim, Hwajung; Yang, Jaeseok; Hwang, Young-Hwan; Ahn, Curie; Oh, Kook-Hwan

    2012-03-01

    Pyruvate is an endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of ethyl pyruvate (EP) against the development and progression of diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-glucose (HG; 50 mM) or normal-glucose (NG; 5 mM) conditions and with or without pyruvate. Pyruvate-treated diabetic rats exhibited decreased albuminuria and attenuated NADPH-dependent reactive oxygen species generation. Immunohistochemistry showed reduced laminin, type IV collagen, and fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue mRNA and protein expression levels of monocyte chemoattractant protein-1, transforming growth factor-β1, laminin, fibronectin, and type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that pyruvate protects against kidney injury via NADPH oxidase inhibition. The present study established that activation of NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular hypertrophy, and ECM molecule expression. Pyruvate exhibited a renoprotective effect in the progression of experimental diabetic nephropathy. Future research is warranted to investigate the protective mechanism of pyruvate more specifically in relation to NADPH oxidase in diabetic nephropathy.

  15. 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.

  16. 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.

  17. Loss of albumin and megalin binding to renal cubilin in rats results in albuminuria after total body irradiation.

    Science.gov (United States)

    Yammani, Raghunatha R; Sharma, Mukut; Seetharam, Shakuntla; Moulder, John E; Dahms, Nancy M; Seetharam, Bellur

    2002-08-01

    The role of the renal apical brush-border membrane (BBM) endocytic receptors cubilin and megalin in the onset of albuminuria in rats exposed to a single dose of total body irradiation (TBI) has been investigated. Albuminuria was evident as immunoblot (IB) analysis of the urine samples from TBI rats revealed excretion of large amounts of albumin. IB analysis of the BBM proteins did not reveal any significant changes in cubilin or megalin levels, but (125)I-albumin binding to BBM from TBI rats declined by 80% with a fivefold decrease (from 0.5 to 2.5 microM) in the affinity for albumin. IB analysis of cubilin from the BBM demonstrated a 75% loss when purified using albumin, but not intrinsic factor (IF)-cobalamin (Cbl) ligand affinity chromatography. Immunoprecipitation (IP) of Triton X-100 extract of the BBM with antiserum to cubilin followed by IB of the immune complex with an antiserum to megalin revealed a 75% loss of association between megalin and cubilin. IP studies with antiserum to cubilin or megalin and IB with antiserum to the cation-independent mannose 6-phosphate/insulin-like growth factor II-receptor (CIMPR) revealed that CIMPR interacted with both cubilin and megalin. In addition, TBI did not disrupt the association of CIMPR with either cubilin or megalin in BBM. These results suggest that albuminuria noted in TBI rats is due to selective loss of albumin and megalin, but not CIMPR or IF-Cbl binding by cubilin. Furthermore, these results also suggest that albumin and IF-Cbl binding to cubilin occur at distinct sites and that in the rat renal BBM, CIMPR interacts with both cubilin and megalin.

  18. Alpha-thalassemia is associated with a decreased occurrence and a delayed age-at-onset of albuminuria in sickle cell anemia patients.

    Science.gov (United States)

    Nebor, Danitza; Broquere, Cédric; Brudey, Karine; Mougenel, Danielle; Tarer, Vanessa; Connes, Philippe; Elion, Jacques; Romana, Marc

    2010-08-15

    The aim of this study was to identify possible risk factors for albuminuria, an early marker of sickle cell anemia (SCA) glomerulopathy, in a cohort of 189 SCA adult patients followed at the Sickle Cell Center of Guadeloupe, a French Caribbean island. Biological parameters obtained at baseline, alpha-globin gene status, and beta(S) haplotypes were compared in patients stratified accordingly to graded albuminuria. Abnormal albumin excretion rate was detected in half of the studied adult patients and macroalbuminuria occurred in 21.6%. Graded albuminuria was associated with advanced age (p=0.006), systolic blood pressure (p=0.031), and worsened anemia, i.e. low hemoglobin rate (pcell count (phaplotype. Our results strongly suggest a protective effect of alpha-thalassemia against glomerulopathy in SCA adult patients which could be related to a decreased hemolytic rate.

  19. 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

  20. 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

  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.

    Directory of Open Access Journals (Sweden)

    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. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

    Science.gov (United States)

    van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew; de Jong, Paul; Gansevoort, Ron T; van der Velde, Marije; Matsushita, Kunihiro; Coresh, Josef; Astor, Brad C; Woodward, Mark; Levey, Andrew S; de Jong, Paul E; Gansevoort, Ron T; Levey, Andrew; El-Nahas, Meguid; Eckardt, Kai-Uwe; Kasiske, Bertram L; Ninomiya, Toshiharu; Chalmers, John; Macmahon, Stephen; Tonelli, Marcello; Hemmelgarn, Brenda; Sacks, Frank; Curhan, Gary; Collins, Allan J; Li, Suying; Chen, Shu-Cheng; Hawaii Cohort, K P; Lee, Brian J; Ishani, Areef; Neaton, James; Svendsen, Ken; Mann, Johannes F E; Yusuf, Salim; Teo, Koon K; Gao, Peggy; Nelson, Robert G; Knowler, William C; Bilo, Henk J; Joosten, Hanneke; Kleefstra, Nanno; Groenier, K H; Auguste, Priscilla; Veldhuis, Kasper; Wang, Yaping; Camarata, Laura; Thomas, Beverly; Manley, Tom

    2011-06-01

    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-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

  7. 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

  8. 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

    hypertension is an early feature of diabetic nephropathy in young insulin-dependent patients. Early and aggressive treatment of that condition decreases albuminuria, probably due to reduced intraglomerular filtration pressure. Whether sustained reduction in arterial blood pressure to near-normal levels during...... 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...... several years also reduces the rate of decline in GFR in diabetic nephropathy remains to be established....

  9. 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

  10. Analysis of the Associations between Vitamin D and Albuminuria or β-Cell Function in Chinese Type 2 Diabetes

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    Xiaoling Cai

    2014-01-01

    Full Text Available Objective. To investigate the associations of 25-(OHD and β-cell function or insulin resistance or albuminuria in Chinese type 2 diabetic patients. Methods. In total, 1408 type 2 diabetic patients without vitamin D supplement were included in this retrospective study. Results. Comparison between patients with and without 25-(OHD deficiency indicated that, compared with patients with 25-(OHD ≥ 50 nmol/L, patients with 25-(OHD < 50 nmol/L showed a higher level of urine albumin-creatinine ratio (ACR (90.15±10.30 mg/g versus 52.79±14.97 mg/g. Multiple regression analysis indicated that 25-(OHD was independently and negatively correlated with urine ACR (OR=0.985, 95%CI 0.972–0.999, P=0.03, adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C, triglyceride, total cholesterol, and HDL-C. Compared with patients with normal level of urine ACR, patients with higher level of urine ACR showed a significant lower level of 25-(OHD (34.49±13.52 nmol/L versus 37.46±13.6 nmol/L, P=0.00. Analysis of the associations of 25-(OHD and β-cell function or insulin resistance showed that 25-(OHD may not correlate with β-cell function or insulin resistance. Conclusion. 25-(OHD was independently associated with albuminuria in Chinese type 2 diabetic patients but was not associated with β-cell function or insulin resistance.

  11. 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.

  12. Chronic administration of EP4-selective agonist exacerbates albuminuria and fibrosis of the kidney in streptozotocin-induced diabetic mice through IL-6.

    Science.gov (United States)

    Mohamed, Riyaz; Jayakumar, Calpurnia; Ramesh, Ganesan

    2013-08-01

    Diabetic nephropathy is currently the most common cause of end-stage renal disease in the western world. Exacerbated inflammation of the kidney is known to contribute acceleration of nephropathy. Despite increased COX-2-mediated production of prostanoid metabolite PGE2, knowledge on its involvement in the progression of diabetic kidney disease is not complete. Here, we show the cross talk of the PGE2-EP4 pathways and IL-6 in inducing albuminuria and fibrosis in an animal model of type 1 diabetes. Hyperglycemia causes enhanced COX-2 expression and PGE2 production. Administration of PGE2 receptor EP4-selective agonist ONO-AE1-329 for 12 weeks exacerbated fibrosis and albuminuria. Diabetes-induced expression of inflammatory cytokines TNFα and TGFβ1 was enhanced in EP4 agonist-treated mice kidney. In addition, urinary excretion of cytokines (TNFα and IL-6) and chemokines (MCP-1 and IP-10) were significantly more in EP4-treated mice than vehicle-treated diabetes. Diabetes-induced collagen I and CTGF expression were also significantly higher in EP4-treated mice. However, EP4 agonist did not alter macrophage infiltration but increased cytokine and chemokine production in RAW264.7 cells. Interestingly, EP4-induced IL-6 expression in the kidney was localized in proximal and distal tubular epithelial cells. To confirm further whether EP4 agonist increases fibrosis and albuminuria through an increase in IL-6 expression, IL-6-knockout mice were administered with EP4 agonist. IL-6-knockout mice were resistant to EP4-induced exacerbation of albuminuria and diabetes and EP4-induced fibrosis. Our data suggest that EP4 agonist through IL-6 induces glomerulosclerosis and interstitial fibrosis, and IL-6 represents a new factor in the EP4 pathway.

  13. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats.

    Science.gov (United States)

    Bardoux, P; Martin, H; Ahloulay, M; Schmitt, F; Bouby, N; Trinh-Trang-Tan, M M; Bankir, L

    1999-08-31

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattleboro rats with diabetes insipidus (DI) lacking VP and in normal Long-Evans (LE) rats, with or without streptozotocin-induced DM. Blood and urine were collected after 2 and 4 weeks of DM, and creatinine clearance, urinary glucose and albumin excretion, and kidney weight were measured. Plasma glucose increased 3-fold in DM rats of both strains, but glucose excretion was approximately 40% lower in DI-DM than in LE-DM, suggesting less intense metabolic disorders. Creatinine clearance increased significantly in LE-DM (P diabetic hyperfiltration and albuminuria induced by DM. This hormone thus seems to be an additional risk factor for diabetic nephropathy and, thus, a potential target for prevention and/or therapeutic intervention.

  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. Development of contrast-induced acute kidney injury after elective contrast media exposure in patients with type 2 diabetes mellitus: effect of albuminuria.

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    Jun-qing Yang

    Full Text Available The influence of albuminuria and urinary pH on the development of contrast-induced acute kidney disease (CI-AKI in patients with type 2 diabetes mellitus (T2DM after elective coronary angiography (CAG or percutaneous coronary intervention (PCI is unknown.CI-AKI was defined as an increase in serum creatinine >26.4 µmol/L or ≥50% of baseline value within 48 hours after contrast media exposure. Demographics, traditional risk factors, clinical outcomes and CI-AKI incidence were compared between groups. Univariate analysis and multivariate logistic regression were performed to assess risk factors of CI-AKI.We observed 597 patients with T2DM after CAG or PCI. Patients were divided into 3 groups based on early morning urinary albumin: negative group (urine dipstick negative, n = 483, trace group (urine dipstick trace, n = 60, and positive group (urine dipstick ≥1+, n = 54. CI-AKI occurred in 33 (5.5% patients, including 19 (3.9% in the negativealbuminuria group, 4 (6.7% in the trace group, and 10 (18.5% in the positive group (p< 0.001, respectively. After adjusting for potential confounding risk factors, positive albuminuria (OR = 3.8, 95% CI: 1.5 to 9.2, p = 0.004 and urinary pH<6 (OR = 2.4, 95% CI: 1.1 to 5.1, p = 0.020 remained significantly associated with CI-AKI.Preprocedural albuminuria and urinary pH <6 are independent risk factors of CI-AKI in patients with T2DM undergoing elective cardiac catheterization, and may be used to identify patients at high risk of post-procedural CI-AKI.

  16. Albuminuria and Diabetic Retinopathy in Type 2 Diabetes Mellitus Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetic Study (SN-DREAMS, report 12

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    Rani Padmaja K

    2011-05-01

    Full Text Available Abstract Background The concordance of microalbuminuria and diabetic retinopathy (DR has been well reported in persons with type 1 diabetes; however, for type 2 diabetes, there is paucity of data especially from population-based studies. The aim of this study was to estimate the prevalence of albuminuria (micro - and macroalbuminuria among persons with type 2 diabetes and determine its role as a risk factor for presence and severity of DR. Methods A population-based cross sectional study was conducted in cohort of 1414 subjects with type 2 diabetes from Chennai metropolis. All the subjects underwent comprehensive eye examination including 45 degrees four-field stereoscopic digital photography. DR was clinically graded using Early Treatment Diabetic Retinopathy Study scales. A morning urine sample was tested for albuminuria. Subjects were considered to have microalbuminuria, if the urinary albumin excretion was between 30 and 300 mg/24 hours, and macroalbuminuria at more than 300 mg/24 hours. The statistical software used was SPSS for Windows, Chicago, IL. Student t-test for comparing continuous variables, and χ2 test, to compare proportions amongst groups were used. Results The prevalence of microalbuminuria in the study subjects was 15.9% (226/1414, and that of macroalbuminuria, 2.7% (38/1414. Individuals with macroalbuminuria in comparison to micro- or normoalbuminuria showed a greater prevalence of DR (60.5% vs. 31.0% vs. 14.1%, p Conclusions Every 6th individual in the population of type 2 diabetes is likely to have albuminuria. Subjects with microalbuminuria were around 2 times as likely to have DR as those without microalbuminuria, and this risk became almost 6 times in the presence of macroalbuminuria.

  17. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

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    Tzur Shay

    2012-10-01

    Full Text Available Abstract Background A recent meta-analysis described a variant (p.Ile2984Val in the cubilin gene (CUBN that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly, and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus.

  18. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...

  19. 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

  20. 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

  1. Apolipoprotein B/A-I and total cholesterol/high-density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C-reactive protein

    NARCIS (Netherlands)

    Kappelle, P.J.W.H.; Gansevoort, R. T.; Hillege, J. L.; Wolffenbuttel, B. H. R.; Dullaart, R. P. F.

    2011-01-01

    Background. The total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and apolipoprotein (apo) B/A-I ratios predict major adverse cardiovascular events (MACEs). The extent to which these associations are modified by high-sensitivity C-reactive protein (hs-CRP) and albuminuria is largely

  2. 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.

  3. 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

    , diabetes duration, estimated GFR, UACR, mean arterial pressure, HbA1c , cholesterol, renin-angiotensin-aldosterone system inhibition, anti-hypertensive treatment and smoking (P ...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...... on diabetes duration, gender, HbA1c and normo-, micro- or macroalbuminuria at baseline. Urinary albumin/creatinine ratio (UACR) was measured yearly and annual change assessed from linear regression. RESULTS: CSII- vs. MDI-treated patients were comparable at baseline. After 4 years, HbA1c was 62 ± 11 vs. 68...

  4. 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.

  5. Relationship of Albuminuria and Renal Artery Stent Outcomes: Results From the CORAL Randomized Clinical Trial (Cardiovascular Outcomes With Renal Artery Lesions).

    Science.gov (United States)

    Murphy, Timothy P; Cooper, Christopher J; Pencina, Karol M; D'Agostino, Ralph; Massaro, Joseph; Cutlip, Donald E; Jamerson, Kenneth; Matsumoto, Alan H; Henrich, William; Shapiro, Joseph I; Tuttle, Katherine R; Cohen, David J; Steffes, Michael; Gao, Qi; Metzger, D Christopher; Abernethy, William B; Textor, Stephen C; Briguglio, John; Hirsch, Alan T; Tobe, Sheldon; Dworkin, Lance D

    2016-11-01

    Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease- or kidney disease-related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P=0.02), cardiovascular disease-related death (93% versus 85%; P≤ 0.01), progressive renal insufficiency (91% versus 77%; P=0.03), and overall survival (89% versus 76%; P≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations.

  6. 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.

  7. 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.

  8. 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

    2016-05-26

    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.

  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. 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。

  11. 高龄高血压患者反杓型血压与白蛋白尿的相关性%Correlation of reversed dipper blood pressure and albuminuria in very old patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    邢云利; 王翠英; 孙颖; 陈海平

    2013-01-01

    目的:探讨高龄高血压患者白蛋白尿与血压节律异常的关系。方法选取2012年6月至2013年6月在北京友谊医院住院的70例高龄高血压患者,收集临床资料、尿白蛋白排泄率以及动态血压监测结果。根据尿检结果将其分为白蛋白尿组(n=32)和非白蛋白尿组(n=38)。比较两组之间的白昼平均收缩压(dSBP)和舒张压(dDBP)、夜间平均收缩压(nSBP)和舒张压(nDBP),以及夜间收缩压和舒张压下降率、血压变异曲线。结果白蛋白尿组与非白蛋白尿组间比较,年龄、性别、糖尿病发生率、超敏C反应蛋白、左室射血分数等方面均无明显差异(P>0.05)。与非白蛋白尿组比较,白蛋白尿组患者估测肾小球滤过率(eGFR)明显下降(P<0.05)。动态血压监测结果显示两组患者dSBP和dDBP均在正常范围,且无明显差异(P>0.05),但白蛋白尿组nSBP明显升高(P<0.01)。两组患者非杓型血压节律的发生率无显著差异,白蛋白尿组患者的反杓型曲线比例更高(P<0.01)。结论夜间收缩压升高,即反杓型血压节律,与高龄高血压患者白蛋白尿和eGFR下降高度相关。%Objective To investigate the correlation of albuminuria with ambulatory blood pressure pattern in the very old patients with hypertension. Methods Seventy very old hypertensive subjects admitted to Beijing Friendship Hospital from June 2012 to June 2013 were enrolled in this study. Their clinical data, urinary albumin excretion rate, ambulatory 24-hour blood pressure monitoring results were collected. The patients were divided into albuminuria group (n=32) and non-albuminuria group(n=38) according to the results of urinary test. Day systolic blood pressure(dSBP) and day diastolic blood pressure(dDBP), night systo1ic blood pressure(nSBP) and night diastolic blood pressure(nDBP) were compared between the 2 groups. Night blood pressure descend

  12. Current smoking status may be associated with overt albuminuria in female patients with type 1 diabetes mellitus: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Okada Kenta

    2012-08-01

    Full Text Available Abstract Background There are very few clinical reports that have compared the association between cigarette smoking and microangiopathy in Asian patients with type 1 diabetes mellitus (T1DM. The objective of this study was to assess the relationships between urinary protein concentrations and smoking and gender-based risk factors among patients with T1DM. Methods A cross-sectional study of 259 patients with T1DM (men/women = 90/169; mean age, 50.7 years who visited our hospital for more than 1 year between October 2010 and April 2011 was conducted. Participants completed a questionnaire about their smoking habits. Patient characteristics included gender, age, body mass index, blood pressure, hemoglobin A1c, lipid parameters, and microangiopathy. Diabetic nephropathy (DN was categorized as normoalbuminuria (NA, microalbuminuria (MA, or overt albuminuria (OA on the basis of the following urinary albumin/creatinine ratio (ACR levels: NA, ACR levels less than 30 mg/g creatinine (Cr; MA, ACR levels between 30 and 299 mg/g Cr; and OA, ACR levels over 300 mg/g Cr. Results The percentages of current nonsmokers and current smokers with T1DM were 73.0% (n = 189 and 27.0% (n = 70, respectively. In addition, the percentage of males was higher than that of females (52.2% versus 13.6% in the current smoking population. The percentage of DN was 61.8% (n = 160 in patients with NA, 21.6% (n = 56 in patients with MA, and 16.6% (n = 43 in patients with OA. The percentage of males among OA patients was also higher than that of females (24.4% versus 12.4%. However, current smoking status was associated with OA in females with T1DM only [unadjusted odds ratio (OR, 4.13; 95% confidence interval (CI, 1.45–11.73, P P  Conclusions Based on our results in this cross-sectional study of Asian patients with T1DM, smoking might be a risk factor for OA among female patients. Further research is needed of these gender-specific results.

  13. 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

  14. 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.

  15. 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:

  16. Espironolactona reduz a pressão arterial e a albuminúria de hipertensos obesos com síndrome metabólica Spironolactone reduces blood pressure and albuminuria of obese hypertensive patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Danielle Guedes Andrade Ezequiel

    2013-03-01

    in this syndrome has been suggested. However, the treatment with antagonists of mineralocorticoid receptor in these individuals has not properly addressed. OBJECTIVE: To evaluate the effects of mineralocorticoid receptor blockade on blood pressure, inflammatory, metabolic and renal parameters in non-diabetic hypertensive individuals with the metabolic syndrome. METHODS: Twenty nine patients with metabolic syndrome were enrolled in a prospective protocol that consisted of 2 periods: baseline (2 weeks in which demographic data were obtained and antihypertensive medicines were withdrawn, and treatment period when the individuals were treated with spironolactone 25-50 mg once-a-day, for 16 weeks. In both periods, inflammatory, metabolic and renal parameters were assessed and the 24-hour ambulatory blood pressure monitorization was performed. RESULTS: After spironolactone treatment, 24 hour systolic and diastolic blood pressure decreased from 143.5 ± 15.17 mmHg to 133.2 ± 17.34 mmHg (p = 0.025 and from 85.2 ± 11.10 mmHg to 79.3 ± 11.78 mmHg (p = 0.026, respectively. HDL-cholesterol increased from 44.0 ± 8.67 mg/dl to 49.0 ± 6.75mg/dl (p = 0.000 and C-reactive protein decreased significantly from 6.3 ± 7.54 mg/l to 4.6 ± 6.3 mg/l (p = 0.009. Fasting plasma glucose, insulin, HOMA-IR and triglycerides did not change significantly after mineralocorticoid receptor blockade. Estimated glomerular filtration rate did not change whereas the logarithm of albuminuria decreased significantly from 2.5 ± 0.92 to 2.0 ± 0.9 (p = 0.028. CONCLUSION: In hypertensive subjects with MS the administration of spironolactone in monotherapy was effective for hypertension control, decreased uri nary albumin excretion and increased HDL-cholester ol plasma.

  17. 随机尿白蛋白/肌酐比值对妊娠期高血压疾病的预测价值%Predictive value of random spot albuminuria to creatinine ratio in women with hypertensive disorders complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    阴红; 高云飞; 何淑明; 余艳萍; 黄启涛; 王艳; 孔紫靖; 钟梅

    2015-01-01

    目的:测定正常孕妇的随机尿白蛋白/肌酐比值(albuminuria to creatinine ratio, ACR),追踪妊娠结局,探讨 ACR 对妊娠期高血压疾病( hypertensive disorders complicating pregnancy , HDCP )的预测价值。方法:随机选择正常孕妇,纳入2038例正常孕妇其中87例后期发生HDCP。测定ACR、血尿常规、血生化,尿蛋白阳性者测定24 h 尿蛋白。结果:发生 HDCP 组 ACR 显著增高,24 h 尿蛋白无明显差异;ACR 与24 h 尿蛋白呈正相关;Losigtic 回归分析显示年龄、孕周、ACR、红细胞、血糖、肌酐、总蛋白是发生 HDCP 的独立危险因素; ACR 预测 HDCP 的 ROC 曲线下面积为0.787,敏感度为0.78,特异度为0.63,最佳值为1.46 mg/mmol。结论:ACR 在 HDCP 前期与24 h 尿蛋白呈正相关,较24 h 尿蛋白敏感,可早期预测 HD-CP。%Objective To determine the random spot albuminuria to creatinine ratio (ACR) of normal pregnant women , to track the pregnancy outcome , and to discuss the predictive value of ACR in women with hy-pertensive disorders complicating pregnancy (HDCP). Methods Except for 87 pregnant women suffering from HDCP, 2 038 pregnant women were enrolled in this study. ACR, routine examinations of blood and urine, blood biochemical, 24-hr urinary protein were determined. Results ACR, but not 24-hr urinary protein level,was sig-nificantly higher in women with HDCP. There was positive correlation between the ACR and 24-hr urinary protein quantitation. Age, gestational weeks, ACR, red blood cells, fasting plasma glucose, serum creatinine, total pro-tein were the independent risk factors for HDCP. The sensitivity , specificity and optimal cut off value of ACR for predicting HDCP were 0.78, 0.63, 1.46 mg/mmol. Conclusions There was positive correlation between ACR and 24-hr urinary protein quantitation , and ACR provided a more sensitive pathway for early predictionof HDCP.

  18. Correlation investigation between levels of MMP-2,MMP-3,MMP-10,TIMP-1 and type 1 diabetes with albuminuria%MMP -2、MMP -3、MMP -10及 TIMP -1与1型糖尿病蛋白尿的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱于坚

    2016-01-01

    Objective To investigate the correlation between levels of MMP - 2,MMP - 3,MMP - 10,TIMP - 1 and type 1 diabetes with albuminuria. Methods Fourty patients of type 1 diabetes with microalbuminuria or macroalbuminuria were selected in this study(observa-tion group). Meanwhile 40 healthy people for healthy check in the same period were selected as control group. General information and biochemi-cal indices(HbA1c,LDL,TC,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E - selectin,CRP,IL - 6,TNF - α levels)in two group were compared. Simultaneously,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E - selectin,CRP,IL - 6,TNF - α levels in patients with microalbuminuria and macroalbuminuria were compared. Respectively analysis MMPs and TIMP - 1 and sVCAM - 1 correlation of E- selectin,CRP,IL - 6,TNF - α. Results ①The levels of HbA1c,LDL,TC,MMP - 2,MMP - 3,MMP - 10,TIMP - 1,sVCAM - 1,E- selectin,CRP,IL - 6,TNF - αlevels in observation group were higher than those in control group,showing statistically significant difference( P 0. 05). ③MMP - 10,TIMP - 1 showed a significant positive correlation with sVCAM - 1and E - selectin( P < 0. 05). And MMP - 2 and MMP - 3 was negatively correlated with E - se-lectin and positively correlated with sVCAM - 1. MMP - 3,MMP - 10,TIMP - 1 displayed significantly positive correlation with CRP,TNF - α, IL - 6( P < 0. 05),but MMP - 2 only showed a significant positive correlation with IL - 6,and no significant correlation with CRP and TNF -α. Conclusion MMP - 2,MMP - 3,MMP - 10 and TIMP - 1 were related with albuminuria in type 1 diabetes - related. With the increased levels of albumin excretion,MMP - 2,MMP - 3,MMP - 10 and TIMP - 1 levels were accordingly increased,suggesting their correlation with the severity of albuminuria in type 1 diabetes.%目的探讨基质金属蛋白酶(MMP)-2、MMP -3、MMP -10及基质金属蛋白酶组织抑制因子(TIMP)-1与1型糖尿病蛋白尿的相关性。方法选择40例1型糖尿病伴微量

  19. 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

  20. Albuminuria : A target for treatment of type 2 diabetic nephropathy

    NARCIS (Netherlands)

    de Zeeuw, Dick

    2007-01-01

    Both renal and cardiovascular morbidity and mortality is increased markedly in patients with type 2 diabetes. Besides the classic risk factors and markers such as glucose, blood pressure, blood lipid profile, and lifestyle (smoking, overweight), novel risk markers are identified, among them urine al

  1. 1,25-Vitamin D3 Deficiency Induces Albuminuria.

    Science.gov (United States)

    Sonneveld, Ramon; Hoenderop, Joost G J; Stavenuiter, Andrea W D; Ferrantelli, Evelina; Baltissen, Marijke P A; Dijkman, Henry B; Florquin, Sandrine; Rops, Angelique L; Wetzels, Jack F M; Berden, Jo H M; van der Vlag, Johan; Nijenhuis, Tom

    2016-04-01

    Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin-D3-1α-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.

  2. 1,25-Vitamin D3 Deficiency Induces Albuminuria

    NARCIS (Netherlands)

    Sonneveld, R.; Hoenderop, J.G.; Stavenuiter, A.W.; Ferrantelli, E.; Baltissen, M.P.A.; Dijkman, H.B.; Florquin, S.; Rops, A.; Wetzels, J.F.M.; Berden, J.H.M.; Vlag, J. van der; Nijenhuis, T.

    2016-01-01

    Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1alpha-hydroxy

  3. 受体拮抗剂靶向治疗对糖尿病肾病患者降低蛋白尿疗效分析%Clinical Efficacy of Targeted Therapy with Receptor Antagonist on Albuminuria in Patients with Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    赵林双; 向光大; 浦金辉; 廖玉华; 王敏; 乐岭; 周子华; 孙慧伶; 白伟伟

    2011-01-01

    Objective To investigate the efficacy of targeted therapy of receptor antagonist on albuminuria in patients with diabetic kidney disease.Methods The epitopes of the second extracellular loop of β1 receptor (197-222) and AT1 receptor (165-191) was synthesized and usedrespectively to screen out sera autoantibodies from patients with diabetic nephropathy (n=271) and the control group (n=40) by ELISA.According to the results, the patients with diabetic nephropathy were divided into two groups: the autoantibody positive group (n=171), 71 of them who had both positive of autoantibodies against β1 receptor and AT1 receptor were selected as targeted therapy group and taken target therapy based on conventional treatment; and the autoantibody negative group (n=100), 57 of them who had both negative of autoantibodies against β1 receptor and AT1 receptor were selected as the conventional therapy group.The patients in two group were given the following medication respectively: Metoprolol Tartrate 25-50 mg, po, tid; Valsartan80-160 mg, po, qd; Aspilinl00 mg, po, qd; felodipine 5 mg, po, qd; Hydrochlorothiazide 12.5 mg, po,qd.The hypertension of all subjects was measured before and after 1-4 weeks treatment.The 24-hour urinary protein (UAER) was measured before and after 6-month treatment.Results In patients with diabetic nephropathy, the total positive rate of the autoantibody against β1 receptor and AT1 receptor was 63.1% (171/271) and the positive rate of antibodies both against β1 receptor and AT1 receptor was 41.5%(71/171), all higher than that in the control group (12.5%, 5/40)(P<0.01).The decrease of blood preasure and urine protein were significantly lower than those in the conventional treatment group (P<0.01).Conclusion The findings suggest that these autoantibodies against β1 and AT1-reeeptor may play important roles in the pathogenesis of diabetic nephropathy.Metoprolol Tartrate and Valsartan was shown to be effective and safe in the treatment of

  4. [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.

  5. 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.

  6. 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 and p...

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

    DEFF Research Database (Denmark)

    Christensen, Cramer

    1984-01-01

    .0 micrograms/min X/ divided by 2.6 (2P = 0.01%). In D2 albumin excretion rose from 3.3 micrograms/min X/ divided by 1.9 to 7.9 micrograms/min X/ divided by 1.5 (2P = 0.02%). The albumin excretion in C did not change during exercise. A highly significant correlation between maximal exercise induced systolic...... but without clinical proteinuria). Fifteen male diabetic patients (D3) with a mean age of 26.5 +/- 4.8 years (SD) and a diabetes duration of 15.6 +/- 3.4 years (SD), 11 comparable diabetic patients with normal urinary albumin excretion (D2), and ten non-diabetic subjects (C) were studied. In D3 baseline....../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...

  8. 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.

  9. Cardiovascular autonomic function tests in type 2 diabetes mellitus with micro albuminuria

    Directory of Open Access Journals (Sweden)

    Sudhavana S.

    2012-06-01

    Full Text Available Introduction: Cardiovascular disease is the leading cause of death in type2 diabetes (DM. Microalbuminuria (MAis strongly associated with cardiovascular complications in type2 diabetes. Impaired cardiovascular autonomicfunction and increased albumin excretion are related in patients with diabetes. So this study is designed toinvestigate the relationship between cardiovascular autonomic function and microalbuminuria in type2 diabetes.Methods: The study comprised of 180 subjects of age group>50 years, classified into 3 groups of 60 subjects each.DM without MA, DM with MA and controls. The tests performed were 1 Heart rate response to deep breathing,valsalva maneuver and standing; 2 Blood pressure response to standing and to sustained handgrip. Individual testswere given score of 0, 1, or 2 and an overall autonomic test score of 0-10 was obtained.Results: Mean autonomic score in control, DM without MA and DM with MA are 1.97 ± 0.81, 5.73 ± 1.26 and 7.00± 1.80 respectively. The Coefficient of variation (% of control, DM without MA, DM with MA is 41.1, 21.9 and25.7 respectively. A significant difference in autonomic score was observed in the DM without MA (P<0.01 andDM with MA (P<0.01 when compared to controls.Conclusion: In conclusion type2 diabetic individuals should be diagnosed early to prevent disease progression tomicroalbuminuria and thus minimize complications.

  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

    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...... flow (ERPF) from 465 ml min-1 (412-503) to 410 ml min-1 (385-451) (p Dopamine...... increased ERPF, GFR, CLi, CNa, and decreased the filtration fraction in both environments. Infusion of dopamine further increased Ualb to 10.5 micrograms min-1 (5.5-64.8) (p

  11. 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.; Landová, L.; 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...

  12. Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: Study in vasopressin-deficient Brattleboro rats

    OpenAIRE

    Bardoux, Pascale; Martin, Hélène; Ahloulay, Mina; Schmitt, François; Bouby, Nadine; Trinh-Trang-Tan, Marie-Marcelle; Bankir, Lise

    1999-01-01

    Diabetic nephropathy represents a major complication of diabetes mellitus (DM), and the origin of this complication is poorly understood. Vasopressin (VP), which is elevated in type I and type II DM, has been shown to increase glomerular filtration rate in normal rats and to contribute to progression of chronic renal failure in 5/6 nephrectomized rats. The present study was thus designed to evaluate whether VP contributes to the renal disorders of DM. Renal function was compared in Brattlebor...

  13. 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....

  14. 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...

  15. Do albuminuria and hs-CRP add to the International Diabetes Federation definition of the metabolic syndrome in predicting outcome?

    NARCIS (Netherlands)

    van der Velde, Marije; Bello, Aminu K.; Brantsma, Auke H.; El Nahas, Meguid; Bakker, Stephan J. L.; de Jong, Paul E.; Gansevoort, Ronald T.

    2012-01-01

    Background. To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic syndr

  16. Acute and long-term effect of antihypertensive treatment on exercise-induced albuminuria in incipient diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    1986-01-01

    The aim of the study was to clarify whether antihypertensive treatment could affect the systolic blood pressure (SBP) and urinary albumin excretion (UAE) in diabetics during exercise (450 kpm/min, followed by 600 kpm/min, 20 min each). Young male insulin-dependent diabetics with normal UAE (n = 9......) and diabetics with incipient nephropathy (n = 7) were examined in an acute study. Five patients with incipient diabetic nephropathy participated in a long-term study. Incipient diabetic nephropathy is defined as persistently elevated UAE (greater than 15 micrograms/min), but no clinical proteinuria.......0%). However, no difference was observed in UAE, in patients with normal UAE or those with incipient nephropathy. Five of the patients with incipient nephropathy were followed with repeated exercise tests before and during 2.6 years of antihypertensive treatment, using metoprolol 200 mg/24 h and subsequently...

  17. 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

    cholesterol and triglyceride decreased significantly (P less than 0.01) and the level of HDL cholesterol increased, but not significantly (P = 0.08). In conclusion, treatment of Type 1 diabetic patients, at risk of progressive clinical nephropathy, with the calcium channel blocker, isradipine, had beneficial......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...

  18. 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....

  19. Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist.

    Science.gov (United States)

    Sato, Atsuhisa; Fukuda, Seiichi

    2013-10-01

    We have reported observing aldosterone breakthrough in the course of relatively long-term treatment with renin-angiotensin (RA) system inhibitors, where the plasma aldosterone concentration (PAC) increased following an initial decrease. Aldosterone breakthrough has the potential to eliminate the organ-protective effects of RA system inhibitors. We therefore conducted a study in essential hypertensive patients to determine whether aldosterone breakthrough occurred during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain its clinical significance. The study included 40 essential hypertensive patients (18 men and 22 women) who had been treated for 12 months with aliskiren. Aliskiren significantly decreased blood pressure and plasma renin activity (PRA). The PAC was also decreased significantly at 3 and 6 months; however, the significant difference disappeared after 12 months. Aldosterone breakthrough was observed in 22 of the subjects (55%). Urinary albumin excretion differed depending on whether breakthrough occurred. For the subjects in whom aldosterone breakthrough was observed, eplerenone was added. A significant decrease in urinary albumin excretion was observed after 1 month, independent of changes in blood pressure. In conclusion, this study demonstrated that aldosterone breakthrough occurs in some patients undergoing DRI therapy. Aldosterone breakthrough affects the drug's ability to improve urinary albumin excretion, and combining a mineralocorticoid receptor antagonist with the DRI may be useful for decreasing urinary albumin excretion. When the objective is organ protection in hypertensive patients, a two-pronged approach using combination therapy to inhibit both the RA system and aldosterone may be highly effective.

  20. 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.

  1. initial angiotensin receptor blockade-induced decrease in albuminuria is associated with long-term renal outcome in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Hellemons, Merel E; Persson, Frederik; Bakker, Stephan J L;

    2011-01-01

    We aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria.......We aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria....

  2. 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...

  3. Rationale and design of a study comparing two fixed-dose combination regimens to reduce albuminuria in patients with type II diabetes and hypertension.

    Science.gov (United States)

    Bakris, G L; Toto, R D; McCullough, P A

    2005-02-01

    Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). The early stage of nephropathy is manifested by the presence of low levels of urinary albumin (microalbuminuria or urinary albumin excretion >or=30 and amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide. Other objectives include a comparison of the proportion of patients who progress to overt diabetic nephropathy and the safety of these two combination therapies in these high-risk patients.

  4. Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona

    2017-01-01

    in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine...... the result of an improved glomerular filtration barrier function and generally reduced proteinuria....

  5. 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...

  6. 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...... in patients without albuminuria only diastolic function is affected. Myocardial impairment is detectable many years prematurely in type 1 diabetes, especially in patients with albuminuria....

  7. 糖尿病合并白蛋白尿患者血小板聚集功能和膜蛋白表达的变化%Changes in platelet aggregative function and glycoprotein expression in diabetics with albuminuria

    Institute of Scientific and Technical Information of China (English)

    叶山东; 李素梅; 莫蔚林; 陈超; 陈若平; 戴海明

    2001-01-01

    目的探讨2型糖尿病患者血小板功能改变与血管病变的关系.方法同时测定69例2型糖尿病患者和14例正常人(K组)血小板ADP聚集率和血小板表面颗粒膜蛋白(CD62P和CD63)表达的变化,并根据24小时尿白蛋白排泄量将糖尿病患者分为正常白蛋白尿组(A组)、微量白蛋白尿组(B组)和大量白蛋白尿组(C组).结果与K组比较,B组和C组血小板ADP%显著升高,P值分别小于0.05和小于0.01;A组、B组和C组血小板表面CD62P和CD63表达阳性率,均显著升高,以C组最高;血小板ADP聚集率与CD62P和CD63表达的阳性率呈显著正相关.结论 2型糖尿病患者血小板聚集功能和活化功能显著增强,尤其在伴有白蛋白尿的患者中,并参与血管病变的发生和发展.

  8. 糖尿病合并白蛋白尿病人血小板聚集功能和膜蛋白表达的变化%Changes of platelet aggregative function and glycoprotein expression in diabetics with albuminuria

    Institute of Scientific and Technical Information of China (English)

    叶山东; 李素梅; 戴海明; 莫蔚林; 陈超; 陈若平

    2001-01-01

    目的探讨2型糖尿病病人血小板功能改变与血管病变的关系.方法同时测定69例2型糖尿病病人和14例正常人(K组)血小板ADP聚集率和血小板表面颗粒膜蛋白(CD62P和CD63)表达的变化,并根据24 h尿白蛋白排泄量将糖尿病病人分为正常白蛋白尿组(A组)、微量白蛋白尿组(B组)和大量白蛋白尿组(C组).结果与K组比较,B组和C组血小板ADP百分率显著升高,P值分别小于0.05和小于0.01;A组、B组和C组血小板表面CD62P和CD63表达阳性率均显著升高,以C组最高;血小板ADP聚集率与CD62P和CD63表达的阳性率呈显著正相关.结论2型糖尿病病人血小板聚集功能和活化功能显著增强,尤其在伴有白蛋白尿的病人中,并参与血管病变的发生和发展.

  9. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy.

    Science.gov (United States)

    Fujita, Hiroki; Taniai, Hisanori; Murayama, Hiroko; Ohshiro, Haruyo; Hayashi, Hikaru; Sato, Seiko; Kikuchi, Nyuko; Komatsu, Taiga; Komatsu, Koga; Komatsu, Kanji; Narita, Takuma; Yamada, Yuichiro

    2014-01-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new class of anti-diabetic drug which exerts its glucose-lowering action by suppressing the degradation of a gut incretin hormone glucagon-like peptide-1 (GLP-1). To elucidate whether treatment with stronger DPP-4 inhibitor on top of angiotensin II type 1 receptor blocker (ARB) provides greater renal protective effects, we performed a crossover study with two DPP-4 inhibitors, sitagliptin and alogliptin, in twelve type 2 diabetic patients with incipient nephropathy taking ARBs. This study consisted of three treatment periods: sitagliptin 50 mg/day for 4 weeks (first period), alogliptin 25 mg/day for 4 weeks (second period), and sitagliptin 50 mg/day for 4 weeks (third period). Significant changes in body mass index, blood pressure, serum lipids, serum creatinine, estimated glomerular filtration rate, and HbA1c were not observed among the three treatment periods. Reduced urinary levels of albumin and an oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased urinary cAMP levels, and elevated plasma levels of stromal cell-derived factor-1α (SDF-1α) which is a physiological substrate of DPP-4 were observed after the switch from sitagliptin to a stronger DPP-4 inhibitor alogliptin. Given a large body of evidence indicating anti-oxidative action of cAMP and up-regulation of cellular cAMP production by SDF-1α, the present results suggest that more powerful DPP-4 inhibition on top of angiotensin II type 1 receptor blockade would offer additional protection against early-stage diabetic nephropathy beyond that attributed to glycemic control, via reduction of renal oxidative stress by SDF-1α-cAMP pathway activation.

  10. 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 .

  11. A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years.

    Science.gov (United States)

    Pedersen, E B; Bech, J N; Nielsen, C B; Kornerup, H J; Hansen, H E; Spencer, E S; Sølling, J; Jensen, K T

    1997-12-01

    The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.

  12. 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.

  13. Impedance Cardiographic (ICG) Assessment of Pregnant Women With Severe Hypertension to Assess Impact of Standard Therapy

    Science.gov (United States)

    2013-12-11

    Pregnancy; Proteinuria, With Hypertension (Severe Pre-eclampsia); Delivery; Proteinuria, With Gestational Hypertension (Pre-eclampsia, Severe); Pregnancy; Hypertension, Gestational Hypertension, With Albuminuria (Severe Pre-eclampsia)

  14. 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

  15. 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

    BACKGROUND: A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol...

  16. Renoprotection with and without blood pressure reduction

    NARCIS (Netherlands)

    Laverman, GD; Andersen, S; Rossing, P; Navis, G; de Zeeuw, D; Parving, HH

    2005-01-01

    Background. AT1-receptor blockade dose dependently lowers blood pressure (BP) and albuminuria. Reduction of BP and albuminuria are independent treatment targets for renoprotection, but whether this requires similar dose titration is unknown. Methods. We tested this in two studies designed to find th

  17. 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

  18. 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

  19. 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.

  20. Effects of benazepril on yon Willebrand factor and albuminuria in patients with type 2 diabetes mellitus associated with hypertension%盐酸贝那普利对2型糖尿病并高血压患者血管性血友病因子及尿白蛋白的影响

    Institute of Scientific and Technical Information of China (English)

    李淑英; 魏刚; 李岳华; 冀秋娣

    2008-01-01

    Fifty-six hypertensive diabetic patients (glyeosylated hemoglobin A1c130/80 mm Hg.All the patients were treated for 12 weeks.In both groups,plasma yon Willebrand factor and urine albumin decreased significantly from baseline.Except for urine albumin,no significant inter-group difference in plasma van Willebrand factor and target blood pressure was observed.Benazepril and amledipine seem to show similar efficacy in lowering blood pressure and improving endothelial function,but benazepril may be more effective in kidney protection.%对56例血糖控制达标(糖化血红蛋白<7%)伴白蛋白(ALS)尿的2型糖尿病并高血压患者,分别予盐酸贝那普利(10 ms/d)、氨氯地平(5 mg/d)治疗.治疗后,血浆血管性血友病因子(vWF)浓度和尿ALB含量均有下降(P<0.01);两组间血浆vWF浓度、血压达标率差异无统计学意义,尿ALB含量差异有统计学意义(P<0.05).贝那普利降压及修复内皮损伤与氨氯地平相当,且对肾脏有更好的保护作用.

  1. 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.

  2. 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.

  3. Remission and regression of diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, Peter; Tarnow, Lise; Parving, Hans-Henrik

    2004-01-01

    diabetic patients with overt nephropathy, remission (decrease in albuminuria to diabetic nephropathy (rate of decline in GFR treatment. Furthermore, remission of nephrotic-range albuminuria......Diabetic kidney disease is considered to be an irreversible and inexorable progressive disease. Therefore, prevention of development of ESRD is extremely important. Animal studies have demonstrated that regression of existing renal morphologic lesions is feasible. In a sizable fraction of type 1...... in diabetic patients, an aggressive multifactorial approach, aiming at lowering blood pressure and albuminuria, and improving glycemic control, must be applied....

  4. Comparison of exposure response relationship of atrasentan between North American and Asian populations

    DEFF Research Database (Denmark)

    Heerspink, Hiddo J L; Makino, Hirofumi; Andress, Dennis;

    2016-01-01

    AIMS: The selective endothelin (ET) A receptor antagonist atrasentan has been shown to lower albuminuria in North American and Asian patients with type 2 diabetes and nephropathy. As drug responses to many drugs may differ between North American and Asian populations, we assessed the influence...... of geographical region on the albuminuria and fluid retention response to atrasentan. MATERIALS AND METHODS: Two 12-week double-blind randomised controlled trials were performed with atrasentan 0.75 or 1.25 mg/d vs placebo in patients with type 2 diabetes and nephropathy. The efficacy endpoint was the percentage...... change in albuminuria. Bodyweight change, a proxy of fluid retention, was used as a safety endpoint. Pharmacodynamics were determined in Asians (N = 77) and North Americans (N = 134). Atrasentan plasma concentration was measured in 161 atrasentan-treated patients. RESULTS: Mean albuminuria reduction...

  5. 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

    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......Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol...... 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...

  6. Comparison of effect of nifedipine, labetalol and methyldopa in treatment of hypertension in pregnancy in a tertiary care government hospital

    Directory of Open Access Journals (Sweden)

    Vibhuti Thakur

    2016-01-01

    Conclusions: All three drugs are safe and effective drug in treatment of PIH. Labetalol is more effective in reducing albuminuria as compared to nifedipine and methyldopa. [Int J Reprod Contracept Obstet Gynecol 2016; 5(1.000: 17-22

  7. Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes.

    Science.gov (United States)

    Ruggenenti, Piero; Porrini, Esteban; Motterlini, Nicola; Perna, Annalisa; Ilieva, Aneliya Parvanova; Iliev, Ilian Petrov; Dodesini, Alessandro Roberto; Trevisan, Roberto; Bossi, Antonio; Sampietro, Giuseppe; Capitoni, Enrica; Gaspari, Flavio; Rubis, Nadia; Ene-Iordache, Bogdan; Remuzzi, Giuseppe

    2012-10-01

    Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 μg/min was significantly associated with increased risk compared with albuminuria <1 μg/min (HR, 1.04; 95% CI, 1.02-1.07). This relationship was similar in the subgroup originally randomly assigned to non-ACEI therapy. Among those originally receiving ACEI therapy, however, the event rate was uniformly low and was not significantly associated with albuminuria. Taken together, among normoalbuminuric patients with type 2 diabetes, any degree of measurable albuminuria bears significant cardiovascular risk. The association with risk is continuous but is lost with early ACEI therapy.

  8. Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis

    Science.gov (United States)

    Huang, Rongzhong; Feng, Yuxing; Wang, Ying; Qin, Xiaoxia; Melgiri, Narayan Dhruvaraj; Sun, Yang; Li, Xingsheng

    2017-01-01

    Background Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. Methods MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. Results A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. Conclusions Trandolapril+candesartan appears to be the most efficacious intervention

  9. 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.

  10. [DIABETIC NEPHROPATHY AS A CAUSE OF CHRONIC KIDNEY DISEASE].

    Science.gov (United States)

    Kos, Ivan; Prkačin, Ingrid

    2014-12-01

    Diabetic nephropathy is the leading cause of end-stage chronic kidney disease in most developed countries. Hyperglycemia, hypertension and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Clinical picture includes a progressive increase in albuminuria, decline in glomerular filtration, hypertension, and a high risk of cardiovascular morbidity and mortality. Screening for albuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of adolescence or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with albuminuria should undergo evaluation regarding the presence of associated comorbidities, especially retinopathy and macrovascular disease. Achieving the best metabolic control (HbA1c diabetes.

  11. Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

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    Chunyang Zhang

    2014-01-01

    Full Text Available Glomerular endothelial surface layer (ESL may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM, was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

  12. Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease

    DEFF Research Database (Denmark)

    Jensen, Magnus T; Sogaard, Peter; Andersen, Henrik U;

    2014-01-01

    AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients...... without known heart disease. METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression...... known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared with patients without albuminuria. Echocardiography may be particularly warranted in patients with albuminuria....

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

    DEFF Research Database (Denmark)

    Wachtell, K.; Olsen, M.H.

    2008-01-01

    This Practice Point commentary discusses a recent study by Forman et al. that examined the association between baseline urinary albumin:creatinine ratio and the risk of developing hypertension among 2,179 women in the first and second Nurses' Health Studies who did not have hypertension or diabetes...... 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...

  14. 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.

  15. Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy

    OpenAIRE

    Rossini, Michele; Naito, Takashi; Yang, Haichun; Freeman, Michael; Donnert, Ellen; Ma, Li-Jun; Dunn, Stephen R.; Sharma, Kumar; Fogo, Agnes B.

    2010-01-01

    Background. Sulodexide is a glycosaminoglycan with anticoagulant and antithrombotic activities. Although sulodexide reduced albuminuria in patients with type 1 and type 2 diabetes, long-term effects on chronic renal injury are not established. We investigated sulodexide effects and mechanisms in a rat radiation nephropathy model and in the db/db mouse model of diabetic kidney disease.

  16. Time course of the antiproteinuric and renal haemodynamic responses to losartan in microalbuminuric IDDM

    NARCIS (Netherlands)

    Buter, H; Navis, G; Dullaart, RPF; de Zeeuw, D; de Jong, PE

    2001-01-01

    Background. Interference in the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors has proven to be effective in lowering albuminuria in patients with insulin-dependent diabetes mellitus (IDDM). We studied whether angiotensin II receptor antagonism reduces urinary albumin e

  17. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Holtkamp, Frank A.; Parving, Hans-Henrik; Navis, Gerjan J.; Lewis, Julia B.; Ritz, Eberhard; de Graeff, Pieter A.; de Zeeuw, Dick

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of th

  18. 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

  19. 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

  20. Age and Association of Kidney Measures With Mortality and End-stage Renal Disease

    NARCIS (Netherlands)

    Hallan, Stein I.; Matsushita, Kunihiro; Sang, Yingying; Mahmoodi, Bakhtawar K.; Black, Corri; Ishani, Areef; Kleefstra, Nanne; Naimark, David; Roderick, Paul; Tonelli, Marcello; Wetzels, Jack F. M.; Astor, Brad C.; Gansevoort, Ron T.; Levin, Adeera; Wen, Chi-Pang; Coresh, Josef

    2012-01-01

    Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) by age of the associ

  1. Megalin/Cubulin-Lysosome-mediated Albumin Reabsorption Is Involved in the Tubular Cell Activation of NLRP3 Inflammasome and Tubulointerstitial Inflammation.

    Science.gov (United States)

    Liu, Dan; Wen, Yi; Tang, Tao-Tao; Lv, Lin-Li; Tang, Ri-Ning; Liu, Hong; Ma, Kun-Ling; Crowley, Steve D; Liu, Bi-Cheng

    2015-07-17

    Albuminuria contributes to the development and progression of chronic kidney disease by inducing tubulointerstitial inflammation (TI) and fibrosis. However, the exact mechanisms of TI in response to albuminuria are unresolved. We previously demonstrated that NLRP3 and inflammasomes mediate albumin-induced lesions in tubular cells. Here, we further investigated the role of endocytic receptors and lysosome rupture in NLRP3 inflammasome activation. A murine proteinuric nephropathy model was induced by albumin overload as described previously. The priming and activation signals for inflammasome complex formation were evoked simultaneously by albumin excess in tubular epithelial cells. The former signal was dependent on a albumin-triggered NF-κB pathway activation. This process is mediated by the endocytic receptor, megalin and cubilin. However, the silencing of megalin or cubilin inhibited the albumin-induced NLRP3 signal. Notably, subsequent lysosome rupture and the corresponding release of lysosomal hydrolases, especially cathepsin B, were observed in tubular epithelial cells exposed to albumin. Cathepsin B release and distribution are essential for NLRP3 signal activation, and inhibitors of cathepsin B suppressed the NLRP3 signal in tubular epithelial cells. Taken together, our findings suggest that megalin/cubilin and lysosome rupture are involved in albumin-triggered tubular injury and TI. This study provides novel insights into albuminuria-induced TI and implicates the active control of albuminuria as a critical strategy to halt the progression of chronic kidney disease.

  2. 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

  3. CUBN as a novel locus for end-stage renal disease : insights from renal transplantation

    NARCIS (Netherlands)

    Reznichenko, Anna; Snieder, Harold; van den Born, Jacob; de Borst, Martin H; Damman, Jeffrey; van Dijk, Marcory C R F; van Goor, Harry; Hepkema, Bouke G; Hillebrands, Jan-Luuk; Leuvenink, Henri G D; Niesing, Jan; Bakker, Stephan J L; Seelen, Marcus; Navis, Gerjan

    2012-01-01

    Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage r

  4. CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

    NARCIS (Netherlands)

    Reznichenko, A.; Snieder, H.; Born, J. van den; Borst, M.H. de; Damman, J.; Dijk, M.C.R.F. van; Goor, H. van; Hepkema, B.G.; Hillebrands, J.L.; Leuvenink, H.G.; Niesing, J.; Bakker, S.J.; Seelen, M.; Navis, G.

    2012-01-01

    Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage r

  5. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan

    2016-01-01

    Background: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. W

  6. Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

    NARCIS (Netherlands)

    de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

    2016-01-01

    BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. W

  7. The Dutch hypertension and offspring study : an epidemiological approach to the early pathogenesis of primary hypertension

    NARCIS (Netherlands)

    I.M.S. van Hooft

    1994-01-01

    textabstractMechanisms to explain chronic elevation of blood pressure, hypertension, have been much debated and reviewed. The development ideas can be traced back to the early 19th century, in observations by Bright of an association between high blood pressure and albuminuria. In the more recent p

  8. Prevalence and characteristics of patients with resistant hypertension and chronic kidney disease.

    Science.gov (United States)

    Verdalles, Úrsula; Goicoechea, Marian; Garcia de Vinuesa, Soledad; Quiroga, Borja; Galan, Isabel; Verde, Eduardo; Perez de Jose, Ana; Luño, José

    Resistant hypertension (RH) is a common problem in patients with chronic kidney disease (CKD). A decline in the glomerular filtration rate (GFR) and increased albuminuria are associated with RH; however, there are few published studies about the prevalence of this entity in patients with CKD.

  9. The role of serum β trace protein in the elderly diabetic patients with renal injury

    Institute of Scientific and Technical Information of China (English)

    张欢欢

    2013-01-01

    Objective To study the role of serum β trace protein(βTP) in the evaluation of renal injury in elderly T2DM.Methods The 131 old patients with T2DM were classified into three groups: normal albuminuria group

  10. 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

  11. 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

  12. 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

  13. Impairment of endothelial and subendothelial sites by a circulating plasma factor associated with minimal change disease

    NARCIS (Netherlands)

    Cheung, PK; Baller, JFW; Bakker, WW

    1996-01-01

    Background. The pathogenesis of albuminuria in minimal change disease (MCD) is unknown. A human plasma factor (denoted as 100KF) is able to induce minimal change-like glomerular alterations, i.e. loss of glomerular sialoglycoproteins and decreased expression of glomerular ecto-ATPase, following in v

  14. 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

  15. 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...

  16. 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 ...

  17. 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...

  18. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

    DEFF Research Database (Denmark)

    Nielsen, S E; Schjoedt, K J; Astrup, A S

    2010-01-01

    Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment...... on urinary NGAL was evaluated in diabetic nephropathy....

  19. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension : results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized stu

  20. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized stu

  1. Urinary serine proteases and activation of ENaC in kidney

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Henrik; Nielsen, Lise Hald

    2015-01-01

    -ons. Active plasmin in urine has been demonstrated in diabetes, preeclampsia, and nephrosis. Urine from these patients activates, plasmin-dependently, amiloride-sensitive inward current in vitro. The concept predicts that patients with albuminuria may benefit particularly from reduced salt intake with RAS...

  2. Plasma proteomics classifiers improve risk prediction for renal disease in patients with hypertension or type 2 diabetes

    DEFF Research Database (Denmark)

    Pena, Michelle J; Jankowski, Joachim; Heinze, Georg

    2015-01-01

    and the Steno Diabetes Center. Cases transitioned from normo to microalbuminuria, or from micro to macroalbuminuria. Controls, matched for age, sex, and baseline albuminuria stage, did not transition. Follow-up was 3.0 ± 0.9 years. Plasma proteomics profiles were measured by liquid chromatography-electrospray-trap...

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Vitamin D on early stages of diabetic kidney disease: A cross-sectional study in patients with type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    João Soares Felício

    2016-12-01

    Full Text Available Context: Genetic and environmental factors are involved in the pathogenesis of type 1 diabetes mellitus (T1DM, and vitamin D deficiency appears as a candidate to risk factor for developing diabetic kidney disease (DKD. Objective: The purpose of study was to evaluate the existence of an association between low levels of vitamin D and the presence and degree of DKD in T1DM. Patients and methods: We performed a cross-sectional study, between November 2014 and December 2015. Levels of 25(OHD and albuminuria were analyzed in 37 patients with T1DM and normal glomerular filtration rate. Thirty- six subjects were evaluated as a control group. Results: Patients with T1DM and hypovitaminosis D had higher levels of albuminuria compared to those with normal vitamin D levels (albuminuria (log10 = 1.92 vs 1.44; p <0.05. When we have separated the group of patients according to stage of DKD in patients with normo, micro and macroalbuminuria, there are lower levels of 25(OHD in the last when compared to the first two groups (26.7 ± 6.2, 24.8 ± 7,0 and 15.9 ± 7.6 ng/ml; p <0.05, respectively. In T1DM group, we have found correlations between vitamin D levels and both albuminuria and DKD stages (r= -0.5, p <0.01 and r= -0.4; p <0.05, respectively. A simple linear regression model, with albuminuria as the dependent variable and vitamin D as an independent variable, showed r2= 0.2 and p <0.01. Conclusions: Our data suggest an association between reduced levels of vitamin D and the presence and severity of DKD.

  8. [Diagnosis and management of diabetic nephropathy].

    Science.gov (United States)

    Kitada, Munehiro; Koya, Daisuke

    2015-12-01

    Diabetic nephropathy(DN) is the most common cause of chronic kidney disease, leading to end-stage renal disease (ESRD) and cardiovascular disease (CVD). The overall number of patients with DN will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. The detection of albuminuria is most important for diagnosis of early stage of DN, and also estimated glomerular filtration rate (eGFR) should be assessed, because both albuminuria and reduction of GFR are recognized as the independent risk factor for progression of ESRD and initiation of CVD, respectively. Based on landmark clinical trials, both DN and CVD have become preventable by controlling conventional factors, including hyperglycemia targeting HbA1c<7.0%, hypertenstion using renin angiotensin system inhibitors, dyslipidemia using statins or fibrates, and multifactorial treatment.

  9. CLINICAL GUIDELINE FOR THE TREATMENT OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    R. A. Nadeeva

    2015-01-01

    Full Text Available Due to the high prevalence of diabetes the annual increase of the number of patients with diabetic nephropathy is evidenced. The progressive course of this sequellae and a high percentage of end-stage kidney disease requires a clear approach of early diagnosis, the development of methods of prevention and early treatment from the perspective of evidence-based medicine. This review provides recommendations on glucose-lowering treatment, monitoring of blood pressure and proteinuria, hyperlipidemia. Defi ned individual targets of the correction of hyperglycaemia, depending on the level of albuminuria excretion and the severity of the patient. Indicated the possibilities of applications of certain antidiabetic drugs, depending on the level of glomerular fi ltration rate. Drugs of the fi rst and second line are marked for the selection of antihypertensive treatment. Showed the possible ways to reduce the level of albuminuria. Presented recommendations for the management of patients, depending on the stage of nephropathy.

  10. Increased transvascular lipoprotein transport in diabetes

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...... with type 2 diabetes) and 42 healthy controls. All were randomly recruited. MAIN OUTCOME MEASURE: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL). Autologous 131I-LDL was reinjected iv, and the 1-h fractional escape rate was taken as an index...

  11. Treatment and impact of dyslipidemia in diabetic nephropathy.

    Science.gov (United States)

    Toyama, Tadashi; Shimizu, Miho; Furuichi, Kengo; Kaneko, Shuichi; Wada, Takashi

    2014-04-01

    Recent epidemiological research revealed that dyslipidemia is a risk factor for development and progression of diabetic nephropathy. Results from interventional studies revealed the possibility that anti-hyperlipidemic agents have a better effect on diabetic nephropathy through improvement of albuminuria and loss of renal function. In addition, dyslipidemia may be a consequence of albuminuria and renal dysfunction, thereby perpetuating kidney damage. Today, the proportion of diabetic patients receiving statins is increasing due to their beneficial effect on cardiovascular mortality. However, treatment for patients should be determined based on consideration of the risk and benefit of the treatment. More insight into the pathogenesis of diabetic nephropathy and the effects of life-style changes is required.

  12. 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.

  13. Indirect assessment of eosinophiluria in urinary schistosomiasis using eosinophil cationic protein (ECP) and eosinophil protein X (EPX)

    DEFF Research Database (Denmark)

    Reimert, C M; Ouma, J H; Mwanje, M T;

    1993-01-01

    of infection (eggs/10 ml of urine), albuminuria and pathological changes as detected by ultrasonography. ECP and EPX were determined by means of specific ELISA methods and levels were determined in both urine supernatants and extracted urine deposits (cells and cell debris). The level of ECP was significantly......The pre- and post-treatment level of eosinophiluria, as measured indirectly by the amount of free or cell bound eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in urine from Schistosoma haematobium-infected Kenyan school children, were measured and compared with intensity...... and EPX could be extracted from the urine deposits from infected children, but due to the high amounts of EPX in urine deposit extracts from controls, extracted ECP gave the best discrimination between infected and non-infected children. While albuminuria disappeared in most children at the 6 week post...

  14. 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

  15. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy

    OpenAIRE

    Weil, E. Jennifer; Lemley, Kevin V; Mason, Clinton C; Yee, Berne; Jones, Lois I.; Blouch, Kristina; Lovato, Tracy; Richardson, Meghan; Myers, Bryan D.; Nelson, Robert G.

    2012-01-01

    Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from ten kidney donors (not Americans Indians) showed almost undetectable (0.03%) podocyte detachment a...

  16. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  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.

  18. PROTECTIVE EFFECTS OF METFORMIN IN AN IN VITRO MODEL OF PROTEINURIC KIDNEY DISEASE

    OpenAIRE

    Allouch, Soumaya

    2016-01-01

    Albuminuria, a hallmark of chronic kidney disease (CKD), plays a crucial role in the etiology of CKD. High albumin levels are thought to induce endoplasmic reticulum (ER) stress and activate the AKT pathway, and lead to inactivation of AMP-activated kinase (AMPK), an energy-sensing molecule within cells. This in turn, activates mTOR (mammalian target of rapamycin), which inhibits autophagy and induces epithelial-to-mesenchymal transition (EMT), and ultimately results in accelerated renal cell...

  19. Nuclear cardiology in Senegal: a luxury or a need?; Cardiologie nucleaire au Senegal: un luxe ou une necessite

    Energy Technology Data Exchange (ETDEWEB)

    Mbodj, M.; Seck Gassama, S.; Ndong, B.; Ndoye, O.; Toure Sow, H.; Senghor, S.R. [Universite Cheikh Anta Diop, Lab. Biophysique et Service de Medecine Nucleaire, Faculte de Medecine, de Pharmacie et d' Odontostomatologie, Dakar (UCAD) (Senegal); Diop, S.N. [Centre Antidiabetique Marc Sankale, Hopital Abass Ndao, Dakar (Senegal); Solanki, K.K. [International Atomic Energy Agency, Dept. de la Cooperation Technique, Section Medecine Nucleaire, Vienna (Austria)

    2006-06-15

    Aim: to sensitize at the same time experts and public authorities on the interest of the establishment of nuclear cardiology in Senegal. Material and method: the radioimmunoassay of micro-albuminuria, early marker of cardiovascular morbid-mortality was carried out in the nuclear medicine department of Dakar on a population of 100 diabetic patients (74 of type 1 and 26 of type 2) presenting one or more traditional cardiovascular risk factors. Out of these patients, 39% had abnormal rest ECG, asymptomatic in half of the cases. Results: prevalence of micro-albuminuria is high (24%). There is no significant difference in distribution between type I and type 2. Micro-albuminuria > 30 mg/24 h exists in 16,3% of patients with lipid abnormalities (ratio: total cholesterol/HDL cholesterol > 5), 30% of obese, 75% of hypertensive patients and 43,6% of patients with abnormal rest ECG, who would benefit from myocardial perfusion imaging (MPI): about 17% of patients involved in this study. No or weak correlation is found between micro-albuminuria and traditional risk factors. Conclusion: From these results and available epidemiological data in 2005, the estimate of the requirements in nuclear cardiology for the Senegalese diabetic population, indicates that 3740 patients should have benefited that year from it. Considering that this figure underestimates the real needs, taking into account the needs brought back to a population of 10 million inhabitants and the expect expansion of the diabetic disease, it appears justified to include the nuclear cardiology in the national programmes of prevention of the public health in Senegal. (author)

  20. 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.

  1. 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).

  2. 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.

  3. Renal Dysfunction in the Presence of Normoalbuminuria in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Dwyer, Jamie P; Parving, Hans-Henrik; Hunsicker, Lawrence G;

    2012-01-01

    in type 2 diabetes. METHODS: In the DEMAND (Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes) study, a global, cross-sectional study which described the prevalence and risk factors for albuminuria in a clinic-based cohort, kidney function was assessed...... kidney dysfunction was found in 27% of those with microalbuminuria and 31% of those with overt proteinuria. CrCl was...

  4. 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.

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

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    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.

  6. 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.

  7. 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.

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

    OpenAIRE

    Jae Hee Ahn; Ji Hee Yu; Seung-Hyun Ko; Hyuk-Sang Kwon; Dae Jung Kim; Jae Hyeon Kim; Chul Sik Kim; Kee-Ho Song; Jong Chul Won; Soo Lim; Sung Hee Choi; Kyungdo Han; Bong-Yun Cha; Nan Hee Kim

    2014-01-01

    Background Diabetic 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 de...

  9. N-acetyl-seryl-aspartyl-lysyl-proline attenuates renal injury and dysfunction in hypertensive rats with reduced renal mass: council for high blood pressure research.

    Science.gov (United States)

    Liao, Tang-Dong; Yang, Xiao-Ping; D'Ambrosio, Martin; Zhang, Yanlu; Rhaleb, Nour-Eddine; Carretero, Oscar A

    2010-02-01

    N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring peptide of which the plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme inhibitors. We reported previously that, in models of both hypertension and postmyocardial infarction, Ac-SDKP reduces cardiac inflammation and fibrosis. However, it is unknown whether Ac-SDKP can prevent or reverse renal injury and dysfunction in hypertension. In the present study, we tested the hypothesis that, in rats with 5/6 nephrectomy (5/6Nx)-induced hypertension, Ac-SDKP reduces renal damage, albuminuria, and dysfunction by decreasing inflammatory cell infiltration and renal fibrosis and by increasing nephrin protein. Ac-SDKP (800 microg/kg per day, SC via osmotic minipump) or vehicle was either started 7 days before 5/6Nx (prevention) and continued for 3 weeks or started 3 weeks after 5/6Nx (reversal) and continued for another 3 weeks. Rats with 5/6Nx developed high blood pressure, left ventricular hypertrophy, albuminuria, decreased glomerular filtration rate, and increased macrophage infiltration (inflammation) and renal collagen content (fibrosis). Ac-SDKP did not affect blood pressure or left ventricular hypertrophy in either group; however, it significantly reduced albuminuria, renal inflammation, and fibrosis and improved glomerular filtration rate in both prevention and reversal groups. Moreover, slit diaphragm nephrin protein expression in the glomerular filtration barrier was significantly decreased in hypertensive rats. This effect was partially prevented or reversed by Ac-SDKP. We concluded that Ac-SDKP greatly attenuates albuminuria and renal fibrosis and improves renal function in rats with 5/6Nx. These effects may be related to decreased inflammation (macrophages) and increased nephrin protein.

  10. Administration of Recombinant Soluble Urokinase Receptor Per Se Is Not Sufficient to Induce Podocyte Alterations and Proteinuria in Mice

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Placier, Sandrine; Ploug, Michael

    2014-01-01

    Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increa...... in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria....

  11. A population-based study measuring the prevalence of chronic kidney disease among adults in West Malaysia.

    Science.gov (United States)

    Hooi, Lai Seong; Ong, Loke Meng; Ahmad, Ghazali; Bavanandan, Sunita; Ahmad, Noor Ani; Naidu, Balkish M; Mohamud, Wan Nazaimoon W; Yusoff, Muhammad Fadhli M

    2013-11-01

    In this population-based study, we determine the prevalence of chronic kidney disease in West Malaysia in order to have accurate information for health-care planning. A sample of 876 individuals, representative of 15,147 respondents from the National Health and Morbidity Survey 2011, of the noninstitutionalized adult population (over 18 years old) in West Malaysia was studied. We measured the estimated glomerular filtration rate (eGFR) (CKD-EPI equation); albuminuria and stages of chronic kidney disease were derived from calibrated serum creatinine, age, gender and early morning urine albumin creatinine ratio. The prevalence of chronic kidney disease in this group was 9.07%. An estimated 4.16% had stage 1 chronic kidney disease (eGFR >90 ml/min per 1.73 m(2) and persistent albuminuria), 2.05% had stage 2 (eGFR 60-89 ml/min per 1.73 m(2) and persistent albuminuria), 2.26% had stage 3 (eGFR 30-59 ml/min per 1.73 m(2)), 0.24% had stage 4 (eGFR 15-29 ml/min per 1.73 m(2)), and 0.36% had stage 5 chronic kidney disease (eGFR Malaysia is common and, therefore, warrants early detection and treatment in order to potentially improve outcome.

  12. 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.

  13. Profile of Type 2 Diabetic Patients Referred to Electroneurography Laboratory

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    Ufuk Emre

    2010-05-01

    Full Text Available Objective: In this study, we aimed to assess the presence of minor complications in patients with type 2 diabetes mellitus (DM referred to electroneurography (ENG laboratory for evaluation of neuropathy. In addition, the relationship between duration of disease, electrophysiologic findings, neurological examination findings, plasma glycated hemoglobin A1C levels, glucose levels and microvascular complications were examined. Materials and Methods: One hundred seventy patients with type 2 diabetes were included. Age, gender, duration of disease, results of ophthalmological examinations, neuropathic complaints, electrophysiological examination results, neurological examination findings and laboratory examination results including blood glucose and A1C levels, presence of albuminuria were recorded retrospectively. Results: Abnormal ENG findings were found in one hundred forty patients (82.4%. In all patients, the rate of retinopathy was 34.1% and the rate of albuminuria was 19.4%. The rate of polyneuropathy (PNP( was 78.2% in patients with abnormal neurologic examination. Neuropathic complaints and PNP were found to be related with the presence of retinopathy. The rate of retinopathy was higher in patients with albuminuria. Significant relationship was found between disease duration and retinopathy, PNP and neuropathic complaints. Conclusions: This study emphasizes that detailed history, neurological and ophthalmological examinations are easy, cost-effective and reliable examinations in follow-up of type 2 diabetics. ENG examination, which needs time and money, should be done in asymptomatic cases or for differential diagnosis of neuropathies with clues not related with diabetic neuropathy. Turk Jem 2010; 14: 10-4

  14. Dyslipoproteinemia and impairment of renal function in diabetic kidney disease: an analysis of animal studies, observational studies, and clinical trials.

    Science.gov (United States)

    Hung, Chi-Chih; Tsai, Jer-Chia; Kuo, Hung-Tien; Chang, Jer-Ming; Hwang, Shang-Jyh; Chen, Hung-Chun

    2013-01-01

    Dyslipoproteinemia is highly prevalent in diabetes, chronic kidney disease, and diabetic kidney disease (DKD). Both diabetes and chronic kidney disease (CKD) are associated with hypertriglyceridemia, lower high-density lipoprotein, and higher small, dense low-density lipoprotein. A number of observational studies have reported that dyslipidemia may be associated with albuminuria, renal function impairment, and end-stage renal disease (ESRD) in the general population, and especially in CKD and DKD patients. Diabetic glomerulopathy and the related albuminuria are the main manifestations of DKD. Numerous animal studies support the finding that glomerular atherosclerosis is the main mechanism of glomerulosclerosis in CKD and DKD. Some randomized, controlled trials suggest the use of statins for the prevention of albuminuria and renal function impairment in CKD and DKD patients. However, a large clinical study, the Study of Heart and Renal Protection (SHARP), does not support that statins could reduce ESRD in CKD. In this article, we analyze the complex association of dyslipoproteinemia with DKD and deduce its relevance from animal studies, observational studies, and clinical trials. We show that special subgroups could benefit from the statin treatment.

  15. Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria

    Science.gov (United States)

    Mohammed-Ali, Zahraa; Lu, Chao; Marway, Mandeep K.; Carlisle, Rachel E.; Ask, Kjetil; Lukic, Dusan; Krepinsky, Joan C.; Dickhout, Jeffrey G.

    2017-01-01

    Endoplasmic reticulum (ER) stress is implicated in chronic kidney disease (CKD) development in patients and in animal models. Here we show that ER stress inhibition through 4-phenylbutyric acid (4-PBA) administration decreases blood pressure, albuminuria, and tubular casts in an angiotensin II/deoxycorticosterone acetate/salt murine model of CKD. Lower albuminuria in 4-PBA-treated mice was associated with higher levels of cubilin protein in renal tissue membrane fractions. 4-PBA decreased renal interstitial fibrosis, renal CD3+ T-cell and macrophage infiltration, mRNA expression of TGFβ1, Wnt signaling molecules, and ER stress-induced pro-inflammatory genes. CHOP deficient mice that underwent this model of CKD developed hypertension comparable to wild type mice, but had less albuminuria and tubular casts. CHOP deficiency resulted in higher nephrin levels and decreased glomerulosclerosis compared to wild type mice; this effect was accompanied by lower macrophage infiltration and fibrosis. Our findings portray ER stress inhibition as a means to alleviate hypertensive CKD by preserving glomerular barrier integrity and tubular function. These results demonstrate ER stress modulation as a novel target for preserving renal function in hypertensive CKD. PMID:28148966

  16. 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.

  17. 'Progressive diabetic nephropathy. How useful is microalbuminuria?: contra'.

    Science.gov (United States)

    MacIsaac, Richard J; Ekinci, Elif I; Jerums, G

    2014-07-01

    The concept of microalbuminuria has been central to the development of clinical practice and research in the area of diabetic kidney disease (DKD). However, in recent times, the value of a paradigm of DKD based solely on microalbuminuria has been questioned. Although both the absolute level and rate of change of microalbuminuria are linked to the development and progression of DKD, microalbuminuria on its own lacks the necessary sensitivity or specificity to accurately predict kidney outcomes for people with diabetes. The development of microalbumiuria can no longer be viewed as a committed and irreversible stage of DKD, as spontaneous remission is now reported as a common occurrence. In addition, the absence of microalbuminuria or its progression to proteinuria does not signify that an individual patient is safe from a progressive decline in glomerular filtration rate (GFR). Furthermore, although reductions in albuminuria within the microalbuminuric range can be linked to a slower GFR decline in observational studies, this relationship has not been robustly demonstrated in intervention studies. Conclusions regarding the kidney health of individuals with diabetes will continue to be flawed if an inappropriate emphasis is placed on the presence or absence of albuminuria or changes in albuminuria within the microalbuminuric range. This has important implications in terms of undermining the value of microalbuminuria as a surrogate renal end point for intervention trials. There is a need to develop broader models of progressive DKD that include novel pathways and risk markers apart from those related to the traditional 'albuminuric pathway' to renal impairment.

  18. Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage: anti-inflammatory effect of cholecystokinin.

    Science.gov (United States)

    Miyamoto, Satoshi; Shikata, Kenichi; Miyasaka, Kyoko; Okada, Shinichi; Sasaki, Motofumi; Kodera, Ryo; Hirota, Daisho; Kajitani, Nobuo; Takatsuka, Tetsuharu; Kataoka, Hitomi Usui; Nishishita, Shingo; Sato, Chikage; Funakoshi, Akihiro; Nishimori, Hisakazu; Uchida, Haruhito Adam; Ogawa, Daisuke; Makino, Hirofumi

    2012-04-01

    Inflammatory process is involved in the pathogenesis of diabetic nephropathy. In this article, we show that cholecystokinin (CCK) is expressed in the kidney and exerts renoprotective effects through its anti-inflammatory actions. DNA microarray showed that CCK was upregulated in the kidney of diabetic wild-type (WT) mice but not in diabetic intracellular adhesion molecule-1 knockout mice. We induced diabetes in CCK-1 receptor (CCK-1R) and CCK-2R double-knockout (CCK-1R(-/-),-2R(-/-)) mice, and furthermore, we performed a bone marrow transplantation study using CCK-1R(-/-) mice to determine the role of CCK-1R on macrophages in the diabetic kidney. Diabetic CCK-1R(-/-),-2R(-/-) mice revealed enhanced albuminuria and inflammation in the kidney compared with diabetic WT mice. In addition, diabetic WT mice with CCK-1R(-/-) bone marrow-derived cells developed more albuminuria than diabetic CCK-1R(-/-) mice with WT bone marrow-derived cells. Administration of sulfated cholecystokinin octapeptide (CCK-8S) ameliorated albuminuria, podocyte loss, expression of proinflammatory genes, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, CCK-8S inhibited both expression of tumor necrosis factor-α and chemotaxis in cultured THP-1 cells. These results suggest that CCK suppresses the activation of macrophage and expression of proinflammatory genes in diabetic kidney. Our findings may provide a novel strategy of therapy for the early stage of diabetic nephropathy.

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

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    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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. The Trace Element Zinc, Serum Cystatin C in the Early Diagnosis of Diabetic Nephropathy Significance%微量元素锌、血清胱抑素 C在糖尿病肾病早期诊断的意义

    Institute of Scientific and Technical Information of China (English)

    况凡; 杨琼; 吴皖

    2013-01-01

    Objective Study of early diabetic nephropathy ( DN ) of the trace elements of zinc , serum cystatin C ( CysC) , serum creatinine ( SCr) and serum urea ( BUN) changes and significance of levels . Method The patients with diabetic nephropathy were divided into 3 groups: normal albuminuria group , microalbuminuria group , clinical albuminuria group .All patients and controls were fasting venous blood trace elements zinc, serum cystatin C, serum urea, serum creatinine.Result Normal albuminuria group, microalbuminuria group , clinical albuminuria group of trace elements zinc was significantly lower than that in normal control group , the difference was statistically significant ( P <0.05 ) .Normal albuminuria group , microalbuminuria group , clinical albuminuria group serum cystatin C levels were significantly higher than those in normal control group , the difference was statistically significant ( P<0.05 ) .Serum creatinine microalbuminuria group , clinical albuminuria group detection value and normal control group have obvious difference , the difference was statistically significant ( P <0.05 ) . Conclusion Has high clinical value in the detection of trace elements zinc , serum cystatin C in early renal damage in diabetic nephropathy , can be used as a reference index for diagnosis of early diabetic nephropathy .%目的:探讨早期糖尿病肾病患者( DN)的微量元素锌、血清胱抑素C( CysC)、血清肌酐( SCr)和血清尿素( BUN)水平的变化程度及意义。方法将糖尿病肾病患者分为3组:正常蛋白尿组,微量蛋白尿组,临床蛋白尿组。所有患者和对照组均空腹抽取静脉血检测微量元素锌、血清胱抑素C、血清尿素、血清肌酐。结果正常蛋白尿组、微量蛋白尿组、临床蛋白尿组微量元素锌均明显低于正常对照组,差异有统计学意义( P<0.05)。正常蛋白尿组、微量蛋白尿组、临床蛋白尿组血清胱抑素C水平均明显高于

  6. 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.

  7. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

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    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

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

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    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.

  9. 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

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

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    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.

  11. 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.

  12. 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.

  13. 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.

  14. Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes

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    Hye Won Lee

    2016-12-01

    Full Text Available BackgroundNonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD event in Korean patients with type 2 diabetes mellitus (T2DM.MethodsLaboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events.ResultsNonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m2, and albuminuria.ConclusionThe results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

  15. Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

    Science.gov (United States)

    Almualm, Yasmin; Zaman Huri, Hasniza

    2015-01-01

    Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR 60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

  16. 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.

  17. Perindopril treatment in streptozotocin induced diabetic nephropaty.

    Science.gov (United States)

    Trojacanec, J; Zafirov, D; Labacevski, N; Jakjovski, K; Zdravkovski, P; Trojacanec, P; Petrusevska, G

    2013-01-01

    Diabetic nephropathy (DN) is one of the most common causes of terminal stadium damage to the kidneys. The angiotensin-converting enzyme (ACE) represents a significant risk factor for the progression of DN. ACE inhibitors are medications of particular interest knowing the role of angiotensin II in the development of DN. This study aimed to examine the effects of ACE inhibitor treatment perindopril (PER), administered to rats with streptozotocin (STZ) induced DN, that developed albuminuria, renal hypertrophy and mild glomerulussclerosis. DN was induced by a STZ (60 mg/kg ip) single injection to normotensive Wistar rats. The administration of STZ caused diabetes mellitus (DM) with symptoms and signs of DN including poor general condition, body-weight loss, kidney weight increase as well as increased values of BUN and serum creatinine, accompanied by increased diuresis as well as distinct albuminuria. The majority of these symptoms were manifested 4 weeks after, and even more distinctly 8 and 12 weeks after administering STZ. The perindopril treatment (6 mg/kg BW), starting 4 weeks after administering STZ, resulted in a significant improvement of all symptoms and signs of DN, significantly lowering the values of BUN and serum creatinine, albuminuria and diuresis. The histopathological examination of the renal samples at 8 and 12 weeks after the beginning of the study have shown that perindopril significantly lowers the progression of glomerulopathy, and significantly improves the glomerulosclerotic index, as well as the progression of renal histological abnormalities induced with STZ. Thus perindopril treatment ameliorates STZ-induced nephropathic changes in DM rats.

  18. 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

  19. The predictive value of microalbuminuria in IDDM. A five-year follow-up study

    DEFF Research Database (Denmark)

    Almdal, T; Nörgaard, K; Feldt-Rasmussen, B;

    1994-01-01

    OBJECTIVE: To investigate the predictive value of microalbuminuria and the annual increase of albumin excretion as risk factors for diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 5-year follow-up of patients with microalbuminuria (urinary albumin excretion [UAE] = 30-299 mg/24 h) and matched...... patients with normoalbuminuria (UAE analysis of log-transformed UAE on time. This study was conducted at the outpatient clinic of the Steno Diabetes Center...... blood pressure, and a higher incidence of proliferative retinopathy compared with nonprogressors. Multiple regression analysis only identified mean HbAlc as an independent predictor of the rate of progression. Smoking was significantly more prevalent in patients with persistent albuminuria. CONCLUSIONS...

  20. 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

    -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...... 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....

  1. 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...

  2. 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.

  3. Mammary-type myofibroblastoma with the nephrotic syndrome.

    Science.gov (United States)

    Colbert, Gates B; Vankawala, Preksha; Kuperman, Michael B; Mennel, Robert G

    2016-07-01

    We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including 9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern.

  4. EFFICACY OF RIBAVIRIN IN EPIDEMIC HEMORRHAGIC FEVER%病毒唑治疗流行性出血热的疗效观察

    Institute of Scientific and Technical Information of China (English)

    罗端德; 王心禾; 蔡淑清; 刘世威; 韦克奇; 夏金生

    1986-01-01

    Seventy-two early cases of epidemic hemorrhagic fever(EHF)were randomly divided into 2 groups;38 cases were treated with ribavirin and 34 oases served as control.The study group received ribavirin 700~750mg/day iv infusion for 3 days,while the control group was treated with symptomatio therapy only.In the study group,fever lowered and albu-minuria disappeared more rapidly, other clinical symptoms were recovered much quicker and specific circulating immune complexes persisted shorter.These results showed that ribavirin has definite effect in the treatment of EHF.

  5. 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-

  6. 糖尿病肾病患者维生素D结合蛋白水平及影响因素研究%Vitamin D Binding Protein Levels in Patients With Diabetic Nephropathy and Its Influencing Factors

    Institute of Scientific and Technical Information of China (English)

    王媛; 史慧婷; 姜书宁; 赵久阳

    2015-01-01

    目的:探讨糖尿病肾病( DN)患者维生素D结合蛋白( VDBP)水平及其影响因素,以明确VDBP与DN的关系,为DN的诊断及治疗提供新的依据。方法选取2013年8月—2014年2月在大连医科大学附属二院住院的2型糖尿病(T2DM)患者66例。根据尿微量清蛋白与尿肌酐比值(UACR)将患者分为3个亚组:正常清蛋白尿组( UACR300 mg/g),各22例。同时选取该院门诊的健康体检者20例为健康对照组。采用酶联免疫吸附试验( ELISA )法检测4组受试者血、尿VDBP水平,同时检测其相关生化指标:空腹血糖( FPG)、糖化血红蛋白( HbA1c )、血尿素( UREA)、血肌酐( SCr)、总胆固醇( TC)、三酰甘油( TG)、高密度脂蛋白胆固醇( HDL-C)、低密度脂蛋白胆固醇( LDL-C)、血清蛋白( ALB)及尿微量清蛋白、尿肌酐。结果健康对照组及正常、微量、临床清蛋白尿组血 VDBP 水平分别为:(44.83±15.65)、(312.25±29.57)、(330.92±49.28)、(338.30±50.05) mg/L,4组间差异有统计学意义(F=409.42, P0.05)。健康对照组及正常、微量、临床清蛋白尿组尿VDBP水平分别为:(5.26±1.34)、(8.93±3.17)、(15.19±3.38)、(21.48±7.00) mg/L,4组间差异有统计学意义(F =58.66, P300 mg/g ) , with 22 patients in each group. We also enrolled 20 healthy people who received outpatient service as control group. ELISA method was employed to detect the serum and urine VDBP level of the subjects, and biochemical indexes were measured, including FPG, HbA1c , UREA, SCr, TC, TG, HDL-C, LDL-C, ALB, UALB, UCR. Results The serum VDBP levels of control group, normal albuminuria group, slight albuminuria group and clinical albuminuria group were (44. 83 ±15. 65), (312. 25 ±29. 57), (330. 92 ±49. 28) and (338. 30 ±50. 05) mg/L respectively, with significant differences among the four groups ( F =409. 42, P 0. 05) . The urine VDBP levels of control group, normal albuminuria group, slight

  7. 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

  8. Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

    Science.gov (United States)

    Albrecht, Thomas; Schilperoort, Maaike; Zhang, Shiqi; Braun, Jana D.; Qiu, Jiedong; Rodriguez, Angelica; Pastene, Diego O.; Krämer, Bernhard K.; Köppel, Hannes; Baelde, Hans; de Heer, Emile; Anna Altomare, Alessandra; Regazzoni, Luca; Denisi, Alessandra; Aldini, Giancarlo; van den Born, Jacob; Yard, Benito A.; Hauske, Sibylle J.

    2017-01-01

    We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman’s capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes. PMID:28281693

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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

  12. Addition of Aliskiren to Angiotensin Receptor Blocker Improves Ambulatory Blood Pressure Profile and Cardiorenal Function Better than Addition of Benazepril in Chronic Kidney Disease

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    Satoshi Umemura

    2013-07-01

    Full Text Available An altered ambulatory blood pressure (BP and heart rate (HR profile is related to chronic kidney disease (CKD and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18 or the benazepril add-on group (n = 18. Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles.

  13. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome.

    Science.gov (United States)

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Antignac, Corinne; Esquivel, Ernie L

    2009-10-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling.

  14. 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.

  15. Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus

    Science.gov (United States)

    Guthoff, Martina; Wagner, Robert; Randrianarisoa, Elko; Hatziagelaki, Erifili; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heyne, Nils

    2017-01-01

    Early identification of patients at risk of developing diabetic nephropathy is essential. Elevated serum concentrations of soluble urokinase receptor (suPAR) associate with diabetes mellitus and predict onset and loss of renal function in chronic kidney disease. We hypothesize, that suPAR may be an early risk indicator for diabetic nephropathy, preceding microalbuminuria. The relationship of baseline suPAR and incident microalbuminuria was assessed in a prospective long-term cohort of subjects at increased risk for type 2 diabetes (TULIP, n = 258). Association with albuminuria at later stages of disease was studied in a cross-sectional cohort with manifest type 2 diabetes (ICEPHA, n = 266). A higher baseline suPAR was associated with an increased risk of new-onset microalbuminuria in subjects at risk for type 2 diabetes (hazard ratio 5.3 (95% CI 1.1–25.2, p = 0.03) for the highest vs. lowest suPAR quartile). The proportion of subjects with prediabetes at the end of observation was higher in subjects with new-onset microalbuminuria. suPAR consistently correlated with albuminuria in a separate cohort with manifest type 2 diabetes. Elevated baseline suPAR concentrations independently associate with new-onset microalbuminuria in subjects at increased risk of developing type 2 diabetes. suPAR may hence allow for earlier risk stratification than microalbuminuria. PMID:28091558

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  18. Increased urinary lysophosphatidic acid in mouse with subtotal nephrectomy: potential involvement in chronic kidney disease.

    Science.gov (United States)

    Mirzoyan, Koryun; Baïotto, Anna; Dupuy, Aude; Marsal, Dimitri; Denis, Colette; Vinel, Claire; Sicard, Pierre; Bertrand-Michel, Justine; Bascands, Jean-Loup; Schanstra, Joost P; Klein, Julie; Saulnier-Blache, Jean-Sébastien

    2016-12-01

    Increased incidence of chronic kidney disease (CKD) with consecutive progression to end-stage renal disease represents a significant burden to healthcare systems. Renal tubulointerstitial fibrosis (TIF) is a classical hallmark of CKD and is well correlated with the loss of renal function. The bioactive lysophospholipid lysophosphatidic acid (LPA), acting through specific G-protein-coupled receptors, was previously shown to be involved in TIF development in a mouse model of unilateral ureteral obstruction. Here, we study the role of LPA in a mouse subjected to subtotal nephrectomy (SNx), a more chronic and progressive model of CKD. Five months after surgical nephron reduction, SNx mice showed massive albuminuria, extensive TIF, and glomerular hypertrophy when compared to sham-operated animals. Urinary and plasma levels of LPA were analyzed using liquid chromatography tandem mass spectrometry. LPA was significantly increased in SNx urine, not in plasma, and was significantly correlated with albuminuria and TIF. Moreover, SNx mice showed significant downregulation in the renal expression of lipid phosphate phosphohydrolases (LPP1, 2, and 3) that might be involved in reduced LPA bioavailability through dephosphorylation. We concluded that SNx increases urinary LPA through a mechanism that could involve co-excretion of plasma LPA with albumin associated with a reduction of its catabolism in the kidney. Because of the previously demonstrated profibrotic activity of LPA, the association of urinary LPA with TIF suggests the potential involvement of LPA in the development of advanced CKD in the SNx mouse model. Targeting LPA metabolism might represent an interesting approach in CKD treatment.

  19. 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.

  20. 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.

  1. 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.

  2. Podocin Inactivation in Mature Kidneys Causes Focal Segmental Glomerulosclerosis and Nephrotic Syndrome

    Science.gov (United States)

    Mollet, Géraldine; Ratelade, Julien; Boyer, Olivia; Muda, Andrea Onetti; Morisset, Ludivine; Lavin, Tiphaine Aguirre; Kitzis, David; Dallman, Margaret J.; Bugeon, Laurence; Hubner, Norbert; Gubler, Marie-Claire; Esquivel, Ernie L.

    2009-01-01

    Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling. PMID:19713307

  3. Effect of Pentoxifylline on Microalbuminuria in Diabetic Patients: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shahrzad Shahidi

    2015-01-01

    Full Text Available Background. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. Human studies have proved its antiproteinuric effect in patients with glomerular diseases, but this study was designed to assess the effects of add-on pentoxifylline to available treatment on reduction of microalbuminuria in diabetic patients without glomerular diseases. Methods. In a double-blind placebo-controlled, randomized study we evaluated the influence of pentoxifylline on microalbuminuria in type 2 diabetic patients. 40 diabetic patients with estimated glomerular filtration rate (eGFR of more than 60 mL/min/1.73 m2 in eight weeks and microalbuminuria were randomized to two groups which will receive pentoxifylline 1200 mg/day or placebo added to regular medications for 6 months. albuminuria; eGFR was evaluated at three- and six-month follow-up period. Results. Baseline characteristics were similar between the two groups. At six months, the mean estimated GFR and albuminuria were not different between two groups at 3- and 6-month follow-up. Trend of albumin to creatinine ratio, systolic and diastolic blood pressure, and eGFR in both groups were decreased, but no significant differences were noted between two groups (P value > 0.05. Conclusion. Pentoxifylline has not a significant additive antimicroalbuminuric effect compared with placebo in patients with type 2 diabetes with early stage of kidney disease; however, further clinical investigations are necessary to be done.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Spontaneous decline in exercise-induced proteinuria during a 100-mile triathlon.

    Science.gov (United States)

    Edes, T E; Shah, J H; Thornton, W H

    1990-09-01

    To study the effect of prolonged exercise on glomerular permeability and proteinuria, we collected serial urine samples from six athletes during a 100-mile triathlon. Urine collected just before, at the midpoint of, and immediately after the race was analyzed for creatinine by an automated chemistry analyzer, pack method, and for microalbumin by radioimmunoassay. By midrace, the urinary albumin-creatinine ratio increased from the prerace mean +/- SEM of 3.5 +/- 0.5 to 38.3 +/- 11.7 mg/g. The ratio then declined to 12.5 +/- 2.7 mg/g by the end of the race (P less than .04). Similarly, the urinary albumin level increased significantly from 5.9 +/- 0.7 to 80.5 +/- 26.8 micrograms/mL by midrace, followed by a decline to 39.2 +/- 12.9 micrograms/mL. The initial increase in albuminuria was expected and reflects the increase in exercise-induced cardiac output and glomerular permeability. The subsequent decline in albuminuria and albumin-creatinine ratio, despite continued exercise, was unexpected and indicates a decrease in glomerular permeability. Further study is warranted to determine the mechanism of this apparently protective renal response to prolonged exercise.

  8. 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

  9. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy

    DEFF Research Database (Denmark)

    Packham, David K; Wolfe, Rory; Reutens, Anne T

    2012-01-01

    Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has been reported to reduce albuminuria in patients with diabetes, but it is unknown whether it is renoprotective. This study reports the results from the randomized, double-blind, placebo-controlled, sulode......Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has been reported to reduce albuminuria in patients with diabetes, but it is unknown whether it is renoprotective. This study reports the results from the randomized, double-blind, placebo......-controlled, sulodexide macroalbuminuria (Sun-MACRO) trial, which evaluated the renoprotective effects of sulodexide in patients with type 2 diabetes, renal impairment, and significant proteinuria (>900 mg/d) already receiving maximal therapy with angiotensin II receptor blockers. The primary end point was a composite...... sulodexide and placebo; the primary composite end point occurred in 26 and 30 patients in the sulodexide and placebo groups, respectively. Side effect profiles were similar for both groups. In conclusion, these data do not suggest a renoprotective benefit of sulodexide in patients with type 2 diabetes, renal...

  10. JC polyoma virus interacts with APOL1 in African Americans with nondiabetic nephropathy.

    Science.gov (United States)

    Divers, Jasmin; Núñez, Marina; High, Kevin P; Murea, Mariana; Rocco, Michael V; Ma, Lijun; Bowden, Donald W; Hicks, Pamela J; Spainhour, Mitzie; Ornelles, David A; Kleiboeker, Steven B; Duncan, Kara; Langefeld, Carl D; Turner, Jolyn; Freedman, Barry I

    2013-12-01

    Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

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

    Science.gov (United States)

    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

  12. [Medical significance of endothelial glycocalyx. Part 2: Its role in vascular diseases and in diabetic complications].

    Science.gov (United States)

    Frati Munari, Alberto C

    2014-01-01

    Endothelial glycocalyx is a layer composed by glycosaminoglycans, proteoglycans and glycoproteins attached to the vascular endothelial luminal surface. Shredding of glycocalyx appears as an essential initial step in the pathophysiology of atherosclerosis and microangiopathic complications of diabetes mellitus, as well as in chronic venous disease. Atherosclerosis risk factors, as hypercholesterolemia (LDL), hyperglycemia, inflammation, salt excess and altered shear stress can damage glycocalyx. This lead to endothelial dysfunction and allows LDL and leukocytes to filtrate to the subendothelial space initiating atheroma plaque formation. Degradation of glycocalyx in diabetes mellitus is mainly due to oxidative stress and enables protein filtration (albuminuria) and endothelial disorder of microangiopathy. Chronic venous hypertension brings to altered shears stress which results in shredded glycocalyx, this allows leukocytes to migrate into venous wall and initiate inflammation leading to morphologic and functional venous changes of the chronic venous disease. Treatment with glycosaminoglycans (sulodexide) prevents or recovers the damaged glycocalyx and several of its consequences. This drug improves chronic venous disease and promotes healing of chronic venous ulcers. It has also been useful in peripheral arterial obstructive disease and in diabetic nephropathy with albuminuria.

  13. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function.

    Science.gov (United States)

    Dugan, Laura L; You, Young-Hyun; Ali, Sameh S; Diamond-Stanic, Maggie; Miyamoto, Satoshi; DeCleves, Anne-Emilie; Andreyev, Aleksander; Quach, Tammy; Ly, San; Shekhtman, Grigory; Nguyen, William; Chepetan, Andre; Le, Thuy P; Wang, Lin; Xu, Ming; Paik, Kacie P; Fogo, Agnes; Viollet, Benoit; Murphy, Anne; Brosius, Frank; Naviaux, Robert K; Sharma, Kumar

    2013-11-01

    Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal microscopy, and electron paramagnetic resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice. These observations were consistent with an overall reduction of mitochondrial glucose oxidation. Activity of AMPK, the major energy-sensing enzyme, was reduced in kidneys from both diabetic mice and humans. Mitochondrial biogenesis, PDH activity, and mitochondrial complex activity were rescued by treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). AICAR treatment induced superoxide production and was linked with glomerular matrix and albuminuria reduction in the diabetic kidney. Furthermore, diabetic heterozygous superoxide dismutase 2 (Sod2(+/-)) mice had no evidence of increased renal disease, and Ampka2(-/-) mice had increased albuminuria that was not reduced with AICAR treatment. Reduction of mitochondrial superoxide production with rotenone was sufficient to reduce AMPK phosphorylation in mouse kidneys. Taken together, these results demonstrate that diabetic kidneys have reduced superoxide and mitochondrial biogenesis and activation of AMPK enhances superoxide production and mitochondrial function while reducing disease activity.

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

    Science.gov (United States)

    Ishizawa, Keisuke; Izawa-Ishizawa, Yuki; Yamano, Noriko; Urushihara, Maki; Sakurada, Takumi; Imanishi, Masaki; Fujii, Shoko; Nuno, Asami; Miyamoto, Licht; Kihira, Yoshitaka; Ikeda, Yasumasa; Kagami, Shoji; Kobori, Hiroyuki; Tsuchiya, Koichiro; Tamaki, Toshiaki

    2014-01-01

    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.

  15. Increased production of beta2-microglobulin after heart transplantation.

    Science.gov (United States)

    Erez, E; Aravot, D; Erman, A; Sharoni, E; van Oyk, D J; Raanani, E; Abramov, D; Sulkes, J; Vidne, B A

    1998-05-01

    Serum beta2-microglobulin (beta2m) levels were measured to evaluate the state of immunoactivation in stable heart transplant recipients. Serum beta2m and renal function of 29 heart transplant recipients were compared with 16 control subjects, who were age and sex matched, and 11 patients with chronic kidney failure. Serum creatinine and 24-hour urine collection for albuminuria were used as markers of renal impairment. Heart transplant recipients with normal renal function (n = 7) had significantly elevated beta2m levels compared with control subjects: 2.6 +/- 0.9 vs 1.66 +/- 0.32 microg/ml, p < or = 0.05. Heart transplant recipients with impaired renal function (n = 22) had significantly elevated beta2m compared with the chronic kidney failure group: 4.42 +/- 1.3 vs 3.49 +/- 0.66 microg/ml (p < or = 0.05); although there was no significant difference in serum creatinine levels. Albuminuria excretion was significantly elevated in the chronic kidney failure group compared with the heart transplant recipients with impaired renal function (p < or = 0.05). Elevated serum beta2m in heart transplant recipients suggests increased beta2m production, reflecting increased immunoactivation. This observation could be useful in monitoring long-term immunosuppressive therapy.

  16. Determinants of anemia in patients with type 2 diabetes melitus%2型糖尿病患者贫血影响因素

    Institute of Scientific and Technical Information of China (English)

    熊信林; 蔡琳; 罗俊

    2012-01-01

      Objective To evaluate the risk factors of anemia in a diabetic population and to explore the relationship between hemoglobin and clinical parameters. Methods This was a case-control study on risk factors of patients with anemia in type 2 diabetes melitus (T2DM). 108 patients were classified into two groups (case group:54, control group:54), clinical and laboratory data were colected. Results The age、duration of T2DM、creatinine、C-reactive protein、albuminuria of patients who had anemia were significantly higher than in patients without anemia. The levels of Albumin、estimated glomerular filtration rate (eGFR)were lower than the group without anemia. A positive correlation was found between hemoglobin with albumin、eGFR, and a negative correlation was found between hemoglobin levels with duration of T2DM, creatinine, C-reactive protein(CRP), albuminuria and age. Multiple regression analysis identified Albumin, eGFR, albuminuria and duration of T2DM as independent determinants of hemoglobin concentration. Logistic regression analysis showed that albumin, eGFR, albuminuria and duration of T2DM were also predictor for anemia. Conclusion Anemia is a multifactorial result, in evaluating hemoglobin levels in T2DM patients, we must keep in mind that albuminuria, albumin, duration of DM, eGFR ,microinflammation can affect the hemoglobin levels of varying degrees.%  目的评估2型糖尿病患者贫血的影响因素。方法本研究为病例对照研究,108位患者被分为2组:病例组54例,对照组54例,临床和实验室资料被搜集。结果贫血患者的年龄,糖尿病病程,肌酐,C反应蛋白(CRP),尿蛋白是明显高于非贫血患者,白蛋白水平,肌酐清除率明显低于贫血患者,血红蛋白与白蛋白,肌酐清除率正相关;与糖尿病病程,肌酐,CRP,尿蛋白,年龄负相关,多元回归分析显示,白蛋白,肌酐清除率,尿蛋白,糖尿病病程是血红蛋白浓度的影响因子,Logistic回归分析显示,

  17. Chaiges nf serum vitamii D aid bnie turinver markers levels ii elderly tyne 2 diabetes natieits with diabetic ienhrnnathy%老年2型糖尿病肾病患者维生素D及骨转换标志物水平的变化特征

    Institute of Scientific and Technical Information of China (English)

    赵真; 王欢; 卢玉; 王翠英; 黄蔚; 苗也; 刘彦; 郭红; 马清

    2015-01-01

    Objective To investigate the levels of serum 25(OH)D levels,bone turnover markers and bone mineral density and evaluate their relationship in elderly type 2 diabetes patients with diabetic nephropathy. Methnds A total of 246 elderly patients with type 2 diabetes were involved and divided into several groups according to age,serum 25(OH)D levels and albuminuria. The serum concentrations of 25(OH)D,para-thyroid hormone(PTH),osteocalcin(OC),collagen type 1 cross - linked C - telopeptide(CTX)and bone mineral dentistry(BMD)were meas-ured. The relationship among these factors was analyzed statistically. Results The 25(OH)D,OC and CTX levels showed a tendency to decrease with age,while PTH level had a rising trend( P < 0. 05). With the increase of the level of albuminuria,serum 25(OH)D level was gradually de-creased and the difference was statistically significant( P < 0. 05). Compared with the patients in normoalbuminuria group and microalbuminuria group,patients with macroalbuminuria showed lower levels of OC and CTX( P < 0. 05). BMD of lumbar vertebra and femoral neck in the mac-roalbuminuria group was significantly lower than in normoalbuminuria group( P < 0. 05). The 25(OH)D level was negatively correlated with al-buminuria level in type 2 diabetes patients. The OC and CTX levels showed a tendency to decrease with the decrease of 25(OH)D level,and OC level in vitamin D severe deficiency group was significantly lower than in sufficiency group( P < 0. 01). BMD of lumbar vertebra and femoral neck in vitamin D severe deficiency group was significantly lower than in sufficiency group( P < 0. 05). Cniclusini Vitamin D insufficiency is highly prevalent among diabetic nephropathy in type 2 diabetes patients and the 25(OH)D level has some negative correlation with the level of albuminu-ria. Bone metabolism condition is low conversion type,and the bone turnover markers have a certain relationship with albuminuria and 25(OH) D levels. Objective To investigate the levels of

  18. Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects.

    Science.gov (United States)

    Heerspink, Hiddo J L; Desai, Mehul; Jardine, Meg; Balis, Dainius; Meininger, Gary; Perkovic, Vlado

    2017-01-01

    Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m(2) per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m(2) per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m(2) per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.

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

    Directory of Open Access Journals (Sweden)

    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 (

  20. 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

  1. Rodent models of diabetic nephropathy: their utility and limitations

    Directory of Open Access Journals (Sweden)

    Kitada M

    2016-11-01

    Full Text Available Munehiro Kitada,1,2 Yoshio Ogura,2 Daisuke Koya1,2 1Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, 2Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa, Japan Abstract: Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will

  2. Limited Accuracy of Colour Doppler Ultrasound Dynamic Tissue Perfusion Measurement in Diabetic Adults

    Science.gov (United States)

    Stoperka, Felix; Karger, Claudia

    2016-01-01

    Dynamic tissue perfusion measurement (DTPM) is a pre-described and available method in pediatric ultrasound to quantify tissue perfusion in renal Doppler ultrasound by particular video analysis software. This study evaluates DTPM during single and between repeated visits after 6 months, calibrates repeated DTPM within different region of interest (ROI) and compares DTPM with kidney function markers in adult patients with early diabetic nephropathy (n = 17). During repeated measurements, no association of readings at the same patients in the same (n = 3 readings) as well as repeated visit (n = 2 visits) could be retrieved. No association between DTPM, MDRD-GFR, albuminuria, age and duration of diabetes was observed. These negative results are presumably related to inconsistency of DTPM due to non-fixed ROI position as could be shown in calibrating series. Further development of the method should be performed to enable reproducible DTPM readings in adults. PMID:28033403

  3. 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

    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...... 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...... 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...

  4. G protein-coupled receptors: potential therapeutic targets for diabetic nephropathy.

    Science.gov (United States)

    Ding, Hai-Hua; Ni, Wei-Jian; Tang, Li-Qin; Wei, Wei

    2015-12-16

    Diabetic nephropathy, a lethal microvascular complication of diabetes mellitus, is characterized by progressive albuminuria, excessive deposition of extracellular matrix, thickened glomerular basement membrane, podocyte abnormalities, and podocyte loss. The G protein-coupled receptors (GPCRs) have attracted considerable attention in diabetic nephropathy, but the specific effects have not been elucidated yet. Likewise, abnormal signaling pathways are closely interrelated to the pathologic process of diabetic nephropathy, despite the fact that the mechanisms have not been explored clearly. Therefore, GPCRs and its mediated signaling pathways are essential for priority research, so that preventative strategies and potential targets might be developed for diabetic nephropathy. This article will give us comprehensive overview of predominant GPCR types, roles, and correlative signaling pathways in diabetic nephropathy.

  5. 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.

  6. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik;

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis...... of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake...... effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving...

  7. Clinical Proteomics: The Potentiality of Urine Analysis for Understanding Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Massimo Paple

    2013-07-01

    Full Text Available The incidence of diabetic nephropathy (DN is constantly rising in parallel with the prevalence of type 2 diabetes and has been predicted to double within the next 15 years. Albuminuria is considered the earliest putative diagnostic sign of diabetic renal damage but it is poorly associated to the complex histopathological picture of glomerular and tubular damage hence, up to now, the accurate diagnosis of the DN requires renal biopsy. The identification of new biomarkers of DN is an urgent need since the proper management of the DN patients requires early and unbiased diagnosis. The Proteomics approach to the study of the human disease allows a large-scale characterisation of the protein content of a biological sample, and its application to urine may be a challenging but powerful strategy to identify new DN biomarkers. In this review we discuss the main results of a decade of proteomic studies focused on the urinary investigation of diabetic nephropathy.

  8. Importancia clínica de la proteinuria en diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Valentín Figueroa

    2001-06-01

    Full Text Available Justificación: Ante la creciente incidencia de Diabetes Mellitus en la población joven, y en vista del pobre nivel de control metabólico alcanzado mundialmente para dicha enfermedad, es necesario encontrar métodos sencillos, prácticos y a nuestro alcance, para detectar en forma muy temprana la aparición de las complicaciones crónicas propias de la Diabetes. Así se lograría evitar, ó al menos enlentecer, la evolución natural de una enfermedad muy limitante para quien no conoce lo suficiente de cómo vivir con ella, o una vez advertido y debidamente instruido en sus implicaciones, hace caso omiso de lo que se recomienda. Objetivo: Revisar la más reciente evidencia de utilidad y disponibilidad de los distintos métodos de evaluación de la albuminuria, para mejorar el abordaje del paciente diabético, con o sin nefropatía. Metodología: Revisión bibliográfica de publicaciones de los últimos 10 años. Conclusiones: 1 A todo paciente DM Tipo 1 luego de 5 años de ser diagnosticado y a todo paciente DM tipo 2 al momento del diagnóstico, debe realizársele medición de proteinuria. 2 Las tiras reactivas para determinar la micro y macroalbuminuria son confiables en relación con la medición de la orina de 24 horas. 3 Los factores más importantes dentro de la evolución de la nefropatía diabética y que exigen un agresivo manejo son: un buen control metabólico y el manejo antihipertensivo. 4 Los otros factores son importantes, pero su intervención es discutible.Background: Due to the growing incidence of Diabetes Mellitus in a younger population, and in view of the poor level of metabolic control reached worldwide for this illness, it is necessary to find simple and practical methods, within our reach, in order to detect the appearance of the chronic complications of Diabetes in very early stages to avoid or at least slow down the natural evolution of them. Aim: To review the most recent evidence of the utility and readiness of

  9. [Classification of Diabetic Nephropathy 2014].

    Science.gov (United States)

    Haneda, Masakazu; Utsunomiya, Kazunori; Koya, Daisuke; Babazono, Tetsuya; Moriya, Tatsumi; Makino, Hirofumi; Kimura, Kenjiro; Suzuki, Yoshiki; Wada, Takashi; Ogawa, Susumu; Inaba, Masaaki; Kanno, Yoshihiko; Shigematsu, Takashi; Masakane, Ikuto; Tsuchiya, Ken; Honda, Keiko; Ichikawa, Kazuko; Shide, Kenichiro

    2014-01-01

    The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.

  10. Tenofovir induced Fanconi syndrome: A possible pharmacokinetic interaction

    Directory of Open Access Journals (Sweden)

    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.

  11. 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...

  12. 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...

  13. 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...

  14. Race and the insulin resistance syndrome.

    Science.gov (United States)

    Kramer, Holly; Dugas, Lara; Rosas, Sylvia E

    2013-09-01

    Type 2 diabetes remains an important cause of morbidity and mortality. The metabolic syndrome affects 25% of the adult US population based on the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults from the National Cholesterol Education Program. Knowledge on the impact of obesity on metabolic health parameters has increased greatly over the past decade. This review discusses the limitations of the National Cholesterol Education Program metabolic syndrome definition and the racial disparities in the clinical presentation of the insulin resistance syndrome. We also examine the current literature with particular emphasis on albuminuria, nonalcoholic fatty liver disease, and intramyocellular lipid content. This review explores potential environmental and genetic reasons for differences in the manifestation of insulin resistance across racial/ethnic groups and highlights several promising areas for further study.

  15. Statins are independently associated with increased HbA1c in type 1 diabetes - The Thousand & 1 Study

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIMS: Statin use has been associated with increased risk of developing type 2 diabetes (T2DM), and with impaired glycemic control in T2DM patients. The association between statin use and glycemic control in type 1 diabetes (T1DM) is unknown. The association between use of statins and glycemic...... laboratory measurements. Data were analyzed in uni-and multivariable models. RESULTS: Mean age 49.6 years, 53% men, mean diabetes duration 25.5 years, 475 (43.5%) received statins. In baseline analyses statin users tended to be older, have longer diabetes duration, and have more severe kidney disease. Left...... ventricular ejection fraction was not associated with statin use. In multivariable models including age, gender, diabetes duration, BMI, blood pressure, physical activity, family history of cardiovascular disease, physical activity, albuminuria, eGFR, retinopathy, smoking, cholesterol, ejection fraction...

  16. 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...... that consistency and precision depend on which monitor is used. During pregnancy, the reproducibility and specificity depend on the timing and whether measurements are performed repeatedly. Over- and underestimations of blood pressure are typical for 24-h monitoring in high- as well as low risk pregnancies......-risk population is invaluable to protect the mother’s kidney function and, if possible, prolong pregnancy for the benefit of the fetus. Estimates of risk by blood pressure evaluation in these women are influenced by pregnancy per se and diabetes vasculopathy. Several factors have to be considered as few monitors...

  17. Microalbuminuria

    DEFF Research Database (Denmark)

    Parving, Hans-Henrik; Persson, Frederik; Rossing, Peter

    2015-01-01

    Diabetic nephropathy is characterised by persistent albuminuria, elevated blood pressure, relentless decline in GFR and enhanced fatal and nonfatal cardiovascular diseases. Microalbuminuria has been central to the development of clinical practise in prevention and treatment of diabetic nephropathy...... and cardiovascular disease. Treatment-induced and spontaneous remission of microalbuminuria has been reported both in type 1 and type 2 diabetic patients, underlining the importance of sustained elevation of urinary albumin excretion. Recently many new biomarkers have been evaluated in diabetic patients, and apart...... from urinary proteomics, none has yet outperformed Harry Keen's discovery of microalbuminuria as the best screening tool for diabetic nephropathy. Remission of microalbuminuria preserves renal function. Microalbuminuria has also stood the test of time as a valid powerful independent predictor for fatal...

  18. Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders

    DEFF Research Database (Denmark)

    Paulis, Ludovit; Foulquier, Sébastien; Namsolleck, Pawel

    2016-01-01

    Cardiovascular and metabolic disorders, such as hypertension, insulin resistance, dyslipidemia or obesity are linked with chronic low-grade inflammation and dysregulation of the renin-angiotensin system (RAS). Consequently, RAS inhibition by ACE inhibitors or angiotensin AT1 receptor (AT1R......) blockers is the evidence-based standard for cardiovascular risk reduction in high-risk patients, including diabetics with albuminuria. In addition, RAS inhibition reduces the new onset of diabetes mellitus. Yet, the high and increasing prevalence of metabolic disorders, and the high residual risk even....... Therefore, a concept of dual AT1R/AT2R modulation emerges as a putative means for risk reduction in cardio-metabolic diseases. The approach employing simultaneous RAS blockade (AT1R) and RAS stimulation (AT2R) is distinct from previous attempts of double intervention in the RAS by dual blockade. Dual...

  19. The Diagnosis Value of ET-1,Cys-C,RBP and NAG in Patients of Early Diabetic Nephropathy%尿液内皮素-1、胱抑素C、视黄醇结合蛋白和NAG酶对早期糖尿病肾病的诊断价值

    Institute of Scientific and Technical Information of China (English)

    齐昆青

    2014-01-01

    Objective:To evaluate the ET-1,Cys-C,RBP and NAG of early diagnosis in patients with type 2 diabetic nephropathy. Method:88 patients with diabetes were selected in our hospital from January 2010 to December 2012,they were divided into non albuminuria group, microalbuminuria group and clinical albuminuria group according to urinary albumin excretion rate(UAER),30 health physical examination patients were selected as control group,the changes of ET-1,Cys-C,RBP and NAG were measured and compared in four groups.Result:ET-1,Cys-C,RBP and NAG of patients with diabetic nephropathy group were significantly increased(P<0.05),and the indicators of microalbuminuria group and clinical albuminuria group were significantly higher than those in without proteinuria group,the differences were statistically significant(P<0.05);Clinical albuminuria group had the highest positive rate contained ET-1 86.2%,Cys-C 79.3%,RBP 89.7%and NAG 93.1%respectively,and increase of positive rate had certain correlation with the excretion of proteinuria.Conclusion:The ET-1,Cys-C,RBP and NAG are higher in the early diagnosis of type 2 diabetic nephropathy patients in positive detection rate,can be used as a basis of diabetic nephropathy for early diagnosis.%目的:研究尿内皮素(ET-1)、胱抑素C(Cys-C)、视黄醇结合蛋白(RBP)和NAG酶(NAG)检测在2型糖尿病肾病早期的诊断价值。方法:选取本院2010年1月-2012年12月收治的88例糖尿病患者,根据尿白蛋白排泄率(UAER)的测定结果将其分为无白蛋白尿组、微量白蛋白尿组和临床白蛋白尿组,选取同期门诊的30例健康体检者作为对照组,比较4组间ET-1、Cys-C、RBP和NAG的水平变化。结果:糖尿病肾病组患者ET-1、Cys-C、RBP和NAG水平明显升高(P<0.05),且微量白蛋白尿组和临床白蛋白尿组各项指标均明显高于无蛋白尿组,比较差异有统计学意义(P<0.05);临床白蛋白尿组的各项指标阳

  20. 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

  1. 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.......Our longitudinal study of urinary albumin excretion rate in long-term insulin-dependent diabetics without proteinuria (negative albustix) suggests that early detection of patients at high and low risk of developing persistent proteinuria, i.e., diabetic nephropathy, is possible by using a sensitive...... method for albumin determination. Our prospective studies in young insulin-dependent diabetics with diabetic nephropathy show that the rate of decline in glomerular filtration rate (GFR) varies considerably, with a mean of 0.75 ml/min/mo and a range from 0.1 to 1.50 ml/min/mo, and that an increase...

  2. Pleiotropic effects of liraglutide treatment on renal risk factors in type 2 diabetes

    DEFF Research Database (Denmark)

    Zobel, Emilie Hein; von Scholten, Bernt Johan; Lindhardt, Morten

    2017-01-01

    AIMS/HYPOTHESIS: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment...... response by determining if high responders (highest reduction) in each risk factor also had high response in other renal risk factors (cross-dependency). METHODS: Open-label study: 31 type 2 diabetics treated with liraglutide for 7weeks. After 3weeks washout 23 re-started treatment and were followed for 1......year. HbA1c, weight, systolic blood pressure (SBP), urinary albumin excretion rate (UAER) and mGFR ((51)Cr-EDTA) were evaluated. Changes in high (Q4) vs. low responders (Q1-Q3) were compared for each renal risk factor. The effects of treatment/off treatment/re-treatment (off-on/off-on effect) were...

  3. Danish Registry of Childhood and Adolescent Diabetes

    DEFF Research Database (Denmark)

    Svensson, Jannet; Cerqueira, Charlotte; Kjærsgaard, Per

    2016-01-01

    classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy...... experiencing severe hypoglycemia, diabetic nephropathy, and retinopathy. CONCLUSION: The systematic collection of data in DanDiabKids documents improved quality of care over the last 12 years, despite a substantial increase in the number of patients cared for by pediatric departments in Denmark, fulfilling......AIM: The aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes. STUDY POPULATION: The study population consists of all...

  4. The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy

    DEFF Research Database (Denmark)

    Pena, Michelle J; de Zeeuw, Dick; Andress, Dennis

    2017-01-01

    We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, doubl...... diabetes, nephropathy, and eGFR treatment duration with atrasentan are indicated.......-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, four of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and six were reduced in patients with e......We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double...

  5. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran

    1997-01-01

    . Moreover, heparin has been shown to reduce albuminuria in patients with incipient diabetic nephropathy. Although increasing evidence supports the hypothesis that loss of heparan sulfate may play a pathophysiological role in the development of diabetic vascular complications, there are still many unresolved...... problems. What are the mechanisms of action of glycosaminoglycans at the molecular biology level, and how can we select compounds without anticoagulant activity suitable for long-term use in the prevention and treatment of late diabetic complications?......Insulin-dependent diabetic patients with increased urinary albumin excretion are characterized by elevated blood pressure and declining kidney function. In addition, such patients have a high risk of atherosclerotic vascular disease, proliferative retinopathy, and cardiomyopathy, suggesting...

  6. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors have...... and lower GFR were predictors of mortality, whereas albuminuria, HbA1c, and low GFR predicted ESRD. CONCLUSIONS: Overall prognosis has improved considerably with current multifactorial treatment of DN in type 2 diabetes, including long-term RAS inhibition....... become standard of care. RESEARCH DESIGN AND METHODS: All patients with type 2 diabetes and DN (n = 543) at the Steno Diabetes Center were followed during 2000-2010. GFR was measured yearly with 51Cr-EDTA plasma clearance. Annual decline in GFR was determined in patients with at least three measurements...

  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...... Hg. Eight patients received treatment with metoprolol (200-400 mg/day), hydralazine (100-200 mg/day), and furosemide (80-500 mg/day). The untreated control group consisted of eight patients matched for age (mean 32 years), diabetes duration (mean 17 years), and sex (two female and six male patients......). 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. 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

    BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker...... candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1...... and type 2 diabetes, respectively. Most were normotensive, and all had normoalbuminuria (median urinary albumin excretion rate, 5.0 microg/min). INTERVENTION: Candesartan, 16 mg/d increasing to 32 mg/d, versus placebo. Assignment was done centrally using an interactive voice-response system. Patients...

  9. 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

    and duration of diabetes. In addition, U-LFABP was measured in 48 type 1 diabetic patients with diabetic nephropathy in a randomized crossover trial consisting of 2 months of treatment with 20, 40, and 60 mg lisinopril once daily in random order. RESULTS: In the cross-sectional study, levels of U-LFABP were......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 or =300 mg/24 h). A control group consisted of 57 healthy individuals. The groups were matched by sex...

  10. Common drugs for stabilization of renal function in the progression of diabetic nephropathy and their relations with hypertension therapy.

    Science.gov (United States)

    Wang, Yuxuan; Wang, Chengcheng; Zhang, Xiuli; Gu, Harvest F; Wu, Liang

    2017-02-14

    Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discuss the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensin-aldosterone system. We then summarize chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. This review may provide the constructive information for further drug development in diabetic nephropathy.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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...... in oxidative stress, inflammation, and fibrosis, in association with decreased extracellular matrix production. These findings demonstrate that monotherapy of Compound 21 is protective against the progression of experimental diabetic nephropathy by inhibiting renal oxidative stress, inflammation, and fibrosis.......The hemodynamic and nonhemodynamic effects of angiotensin II on diabetic complications are considered to be primarily mediated by the angiotensin II type 1 receptor subtype. However, its biological and functional effect mediated through the angiotensin II type 2 receptor subtype is still unclear...

  13. Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study

    DEFF Research Database (Denmark)

    Persson, F.; Rossing, P.; Hovind, P.

    2008-01-01

    OBJECTIVE: To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors...... and advanced glycation end products (AGE peptides). METHODS: IRMA 2 was a 2-year multicentre, randomized, double-blind trial comparing irbesartan (150 and 300 mg once daily) versus placebo. The primary end-point was time to onset of diabetic nephropathy. Samples from a subgroup from the placebo and the 300 mg...... and vWf predicted the end-point. In addition, endothelial Z-score was associated with progression of albuminuria (p = 0.038). CONCLUSION: Endothelial dysfunction and possibly inflammation are novel predictors of progression to diabetic nephropathy in patients with type 2 diabetes and microalbuminuria...

  14. 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.

  15. 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

    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...... 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....

  16. 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.

  17. Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results.

    Science.gov (United States)

    Wohl, David; Oka, Shinichi; Clumeck, Nathan; Clarke, Amanda; Brinson, Cynthia; Stephens, Jeffrey; Tashima, Karen; Arribas, Jose R; Rashbaum, Bruce; Cheret, Antoine; Brunetta, Jason; Mussini, Cristina; Tebas, Pablo; Sax, Paul E; Cheng, Andrew; Zhong, Lijie; Callebaut, Christian; Das, Moupali; Fordyce, Marshall

    2016-05-01

    In 2 double-blinded Phase 3 trials, 1733 antiretroviral-naive participants were randomized to tenofovir alafenamide (TAF), a tenofovir prodrug versus tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 96 weeks, 86.6% in the TAF arm and 85.2% in the TDF arm had HIV-1 RNA <50 c/mL [difference 1.5%; (95% CI: -1.8% to 4.8%)]. With TAF, there are smaller declines in bone mineral density and more favorable changes in proteinuria, albuminuria, and tubular proteinuria, and no cases of proximal tubulopathy compared with 2 for TDF. These longer-term data support E/C/F/TAF as a safe, well-tolerated, and durable regimen for initial HIV-1 treatment.

  18. Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study.

    Science.gov (United States)

    Post, Frank A; Tebas, Pablo; Clarke, Amanda; Cotte, Laurent; Short, William R; Abram, Michael E; Jiang, Shuping; Cheng, Andrew; Das, Moupali; Fordyce, Marshall W

    2017-02-01

    Tenofovir disoproxil fumarate is associated with renal and bone toxicity. In a single-arm, open-label study of 242 virologically suppressed, HIV-infected participants with creatinine clearance 30-69 mL/min who switched to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, participants had stable creatinine clearance, significant and durable improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001), and significant increases in hip and spine bone mineral density through 96 weeks (P < 0.001). Eighty-eight percent maintained HIV-1 RNA <50 c/mL at week 96. These longer-term results support the use of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-infected individuals with mild-moderately impaired renal function.

  19. GENETICS ASPECTS OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter;

    2016-01-01

    validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. RESULTS: In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1...... to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. METHODS: Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery....... LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally...

  1. [Kidney Disease and Laboratory Examinations--Opening Remarks: For Better Understanding of CKD].

    Science.gov (United States)

    Yoshida, Haruyoshi; Wada, Takashi

    2015-02-01

    Chronic kidney diseases (CKD) have been cited as major risk factors not only for endstage renal failure, but also for the development of cardiovascular diseases and death. In the former criteria for CKD diagnosis (NKF K/DOQI, 2002), estimation of the severity of CKD was simply based on GFR, in order for it to be widely and easily understood by general physicians and patients. Therefore, the use of the CKD guideline without information on the causes and grades of albuminuria was limited for estimation of the prognosis. The revised guideline for CKD diagnosis (KDIGO CKD guideline 2012), with the disease category specified for diabetes mellitus and the different scoring system of microalbuminuria, is presently being effectively utilized by nephrologists as well as general physicians. In this symposium, to advice understanding of the causes and evaluation methods of CKD, speakers were invited to discuss topics in kidney pathology, urine sample examination, urinary biomarkers, and GFR.

  2. Significant natriuretic and antihypertensive action of the epithelial sodium channel blocker amiloride in diabetic patients with and without nephropathy

    DEFF Research Database (Denmark)

    Andersen, Henrik; Hansen, Pernille B L; Bistrup, Claus;

    2016-01-01

    OBJECTIVE: Diabetic nephropathy is associated with aberrant glomerular filtration of serine proteases. The study was designed to test the hypothesis that the epithelial sodium channel is activated proteolytically by urine plasmin in diabetic nephropathy and mediates renal sodium retention. METHODS......: In an open-label intervention study on type 1 diabetes patients on standardized NaCl intake (200 mmol/day) with (n = 15) and without diabetic nephropathy (control, n = 12), urinary Na excretion in response to oral amiloride (20 or 40 mg/day for 2 days) was compared. RESULTS: A total of 27 patients completed...... renal Na excretion, reduced blood pressure, albuminuria, and total and active plasmin in urine. It is concluded that epithelial sodium channel is an attractive target to attain blood pressure control in long-term type I diabetes with no enhanced activity associated with nephropathy....

  3. Association between Parathyroid Hormone, 25 (OH) Vitamin D, and Chronic Kidney Disease: A Population-Based Study

    Science.gov (United States)

    Wang, Wei-Hao; Chen, Li-Wei; Sun, Chiao-Yin; Hsu, Heng-Rong; Chien, Rong-Nang

    2017-01-01

    Identification of the accurate risk factor for CKD remains mandatory to combat the high prevalence of diseases. Growing evidence suggests the association of serum vitamin D with diverse health conditions. However, the relationship between vitamin D, intact parathyroid hormone (PTH), and calcium-phosphate metabolism and development of CKD remains controversial. We conduct this cross-sectional observational study to investigate the association between serum 25 (OH) vitamin D, intact PTH, and calcium and phosphate levels with eGFR and albuminuria, as a surrogate marker of CKD, in a community population. A total of 4080 participants were recruited. The mean age was 58.4 ± 13.3 years and 1480 (36.3%) were men. The mean eGFR was 94.1 ± 26.3 mL/min/1.73 m2. The prevalence of CKD was 19.8%. Serum 25 (OH) vitamin D and log intact PTH levels were inversely correlated with eGFR but positively correlated with log albuminuria. Logistic regression analysis identified the log intact PTH as an independent factor associated with eGFR ≤ 60 mL/min/1.73 m2 and proteinuria. This association was consistent when serum intact PTH was analyzed as continuous as well as categorical variables (as hyperparathyroidism). The relationship remains significant using resampling subset analysis with comparable baseline characteristics and adjustment for 25 (OH) vitamin D, calcium, and phosphate levels. This finding warranted further research to clarify the causal relationship of PTH/25 (OH) vitamin D with the risk of CKD in the general population.

  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. Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy.

    Science.gov (United States)

    Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

    2016-12-04

    Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic

  6. An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease.

    Science.gov (United States)

    Gu, Chunyan; Zhang, Jiandong; Noble, Nancy A; Peng, Xiao-Rong; Huang, Yufeng

    2016-11-01

    While angiotensin II blockade slows the progression of diabetic nephropathy, current data suggest that it alone cannot stop the disease process. New therapies or drug combinations will be required to further slow or halt disease progression. Inhibition of plasminogen activator inhibitor type 1 (PAI-1) aimed at enhancing ECM degradation has shown therapeutic potential in diabetic nephropathy. Here, using a mouse model of type diabetes, the maximally therapeutic dose of the PAI-1-neutralizing mouse monoclonal antibody (MEDI-579) was determined and compared with the maximally effective dose of enalapril. We then examined whether addition of MEDI-579 to enalapril would enhance the efficacy in slowing the progression of diabetic nephropathy. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis associated with increased expression of transforming growth factor (TGF)-β1, PAI-1, type IV collagen, and fibronectin from weeks 18 to 22, which were reduced by MEDI-579 at 3 mg/kg body wt, similar to enalapril given alone from weeks 12 to 22 Adding MEDI-579 to enalapril from weeks 18 to 22 resulted in further reduction in albuminuria and markers of renal fibrosis. Renal plasmin generation was dramatically reduced by 57% in diabetic mice, a decrease that was partially reversed by MEDI-579 or enalapril given alone but was further restored by these two treatments given in combination. Our results suggest that MEDI-579 is effective in slowing the progression of diabetic nephropathy in db/db mice and that the effect is additive to ACEI. While enalapril is renal protective, the add-on PAI-1 antibody may offer additional renoprotection in progressive diabetic nephropathy via enhancing ECM turnover.

  7. Randomized control trial for the assessment of the anti-albuminuric effects of topiroxostat in hyperuricemic patients with diabetic nephropathy (the ETUDE study).

    Science.gov (United States)

    Kato, Sawako; Ando, Masahiko; Mizukoshi, Toshihiro; Nagata, Takanobu; Katsuno, Takayuki; Kosugi, Tomoki; Tsuboi, Naotake; Maruyama, Shoichi

    2016-05-01

    Proteinuria is an established risk factor for diabetic nephropathy. Recent studies indicate that some xanthine oxidase inhibitors have a renoprotective effect. The aim of this study was to assess whether topiroxostat reduces albuminuria in hyperuricemic patients with diabetic nephropathy and overt proteinuria. The ETUDE study is an ongoing 24-week, multicenter, open-label, randomized (1:1), parallel group study involving hyperuricemic patients with diabetic nephropathy (estimated glomerular filtration rate [eGFR] ≥ 20 mL/min/1.73 m(2)) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) < 3.5 g/g Cr). Patients are randomly assigned to high dose (topiroxostat 160 mg daily) or low dose (topiroxostat 40 mg daily) on top of standard of care. The primary endpoint is the change in albuminuria indicated by urine albumin-to-creatinine ratio after 24 treated weeks relative to the baseline values. This trial was registered at the Japanese University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: UMIN 000015403). The background, rationale, and study design of this trial are presented here. Seventy-six patients from four registered facilities have already been enrolled and received at least one dose of topiroxostat. This trial will end in 2017. The ETUDE trial is the first randomized controlled study of topiroxostat in hyperuricemic patients with diabetic nephropathy and overt proteinuria. We will clarify the pleiotropic function of topiroxostat including an anti-albumiuric effect as well as its effects on safely decreasing serum uric acid levels.

  8. Rodent models of diabetic nephropathy: their utility and limitations.

    Science.gov (United States)

    Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

    2016-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic

  9. Diet-induced obesity and kidney disease - In search of a susceptible mouse model.

    Science.gov (United States)

    Wicks, Shawna E; Nguyen, Trang-Tiffany; Breaux, Chelsea; Kruger, Claudia; Stadler, Krisztian

    2016-05-01

    Obesity and metabolic syndrome are independent risk factors for chronic kidney disease, even without diabetes or hyperglycemia. Here, we compare two mouse models that are susceptible to diet-induced obesity: the relatively renal injury resistant C57BL/6J strain and the DBA2/J strain which is more sensitive to renal injury. Our studies focused on characterizing the effects of high fat diet feeding on renal oxidative stress, albuminuria, fibrosis and podocyte loss/insulin resistance. While the C57BL/6J strain does not develop significant pathological changes in the kidney, at least on lard based diets within the time frame investigated, it does show increased renal iNOS and nitrotyrosine levels and elevated mitochondrial respiration which may be indicative of mitochondrial lipid overfueling. Restricting the high fat diet to decrease adiposity decreased the levels of cellular oxidative stress markers, indicating that adiposity-related proinflammatory changes such as increased iNOS levels may trigger similar responses in the kidney. Mitochondrial respiration remained higher, suggesting that eating excess lipids, despite normal adiposity may still lead to renal mitochondrial overfueling. In comparison, DBA/2J mice developed albuminuria on similar diets, signs of fibrosis, oxidative stress, early signs of podocyte loss (evaluated by the markers podocin and WT-1) and podocyte insulin resistance (unable to phosphorylate their glomerular Akt when insulin was given). To summarize, while the C57BL/6J strain is not particularly susceptible to renal disease, changes in its mitochondrial lipid handling combined with the easy availability of transgenic technology may be an advantage to design new knockout models related to mitochondrial lipid metabolism. The DBA/2J model could serve as a basis for studying podocyte insulin resistance and identifying early renal markers in obesity before more severe kidney disease develops. Based on our observations, we encourage further critical

  10. 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.

  11. Olmesartan/amlodipine vs olmesartan/hydrochlorothiazide in hypertensive patients with metabolic syndrome: the OLAS study.

    Science.gov (United States)

    Martinez-Martin, F J; Rodriguez-Rosas, H; Peiro-Martinez, I; Soriano-Perera, P; Pedrianes-Martin, P; Comi-Diaz, C

    2011-06-01

    We studied the effects of treatment with olmesartan/amlodipine and olmesartan/hydrochlorothiazide on inflammatory and metabolic parameters (including new-onset diabetes as a secondary endpoint) in non-diabetic hypertensive patients with metabolic syndrome (MetS). A total of 120 patients with MetS and stage I and II hypertension were randomized to olmesartan 20 mg/amlodipine 5 mg or olmesartan 20 mg/hydrochlorothiazide 12.5 mg. If target systolic blood pressure (<140 mm Hg) was not reached, doses were doubled after 13 weeks; doxazosin 4 mg was added after 26 weeks, and doubled after 39 weeks; follow-up ended at 78 weeks. At each visit, blood pressure (BP), fasting plasma glucose, insulin, adiponectin, tumour necrosis factor-α, C-reactive protein (CRP), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukins-1β, -6 and -8, and albuminuria were measured; BP was similarly reduced in both groups; 80% of patients reached target BP. Reductions in albuminuria were also similar (50%). Only olmesartan/amlodipine reduced the insulin resistance index (24%, P<0.01), increased plasma adiponectin (16%, P<0.05) and significantly reduced all of the inflammation markers studied, except CRP, which showed a similar reduction in each group. The risk of new-onset diabetes was significantly lower with olmesartan/amlodipine (P=0.02). Both olmesartan-based combinations were effective, but the amlodipine combination resulted in metabolic and anti-inflammatory effects that may have advantages over the hydrochlorothiazide combination.

  12. 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.

  13. 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

  14. JS ISH-ISN-3 OPTIMAL TARGETS FOR BP CONTROL IN CKD.

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    Wheeler, David

    2016-09-01

    Hypertension is the most prevalent complication of chronic kidney disease (CKD). Lowering high blood pressure slows progressive loss of kidney function and may also reduce the associated risk of cardiovascular complications, a common cause of premature death in CKD patients.Current International Guidelines produced by Kidney Disease: Improving Global Outcomes (KDIGO) acknowledges that no single BP target is optimal for all CKD patients, and encourages individualization of treatment depending on age, the severity of albuminuria and comorbidities. When published in 2012, the available evidence indicated that in CKD patients without albuminuria, the target BP should be ≤140 mmHg systolic and ≤90 mmHg diastolic. However, in most patients with an albumin excretion rate of ≥30 mg/24 h (i.e., those with both micro- and macroalbuminuria), a lower target of ≤130 mmHg systolic and ≤80 mmHg diastolic was suggested. In achieving BP control, the value of lifestyle changes and the need for multiple pharmacological agents was acknowledged. Use of agents that block the renin-angiotensin-aldosterone system was recommended or suggested in all patients with an albumin excretion rate of ≥30 mg/24 h. Recommendations are almost identical in CKD patients with and without diabetes.Recent data from SPRINT (which included CKD patients) and other clinical trials has led nephrologists to ask whether targets lower than those recommend by KDIGO are appropriate and the guidelines are currently undergoing an update. Controversies remain around discontinuation of ACE/ARB in patients with stage 4-5 CKD and dual renin-angiotensin-aldosterone system blockade.

  15. Exogenous kallikrein protects against diabetic nephropathy.

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    Liu, Wenjuan; Yang, Yeping; Liu, Yemei; Lu, Xiaolan; Guo, Shizhe; Wu, Meng; Wang, Meng; Yan, Linling; Wang, Qinghua; Zhao, Xiaolong; Tong, Xian; Hu, Ji; Li, Yiming; Hu, Renming; Stanton, Robert C; Zhang, Zhaoyun

    2016-11-01

    The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

  16. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus.

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    Bancha Satirapoj

    Full Text Available Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114, microalbuminuria (n=100 and macroalbuminuria (n=114. The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77 ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29 ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19 ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63 ng/mgCr] (P<0.01.Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86, 0.99 (95%CI, 0.98 to 1.00 and 0.95 (95%CI, 0.91 to 0.98, respectively.The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.

  17. Monitoring and managing urinary albumin excretion: practical advice for primary care clinicians.

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    Bakris, George L; Kuritzky, Louis

    2009-07-01

    Albuminuria has a strong, continuous, direct, linear relationship with adverse cardiovascular (CV) outcomes and chronic kidney disease progression. Even at levels below the accepted upper limit of what is considered "normal" daily albumin excretion (albumin excretion level and adverse CV events is evident. Primary care clinicians (eg, physicians, nurse practitioners, physicians' assistants) are usually the first point of contact for patients at risk for CV and kidney disease. Hence, identifying and treating problematic albuminuria levels are important in primary care. Both the American Diabetes Association (ADA) and the National Kidney Foundation (NKF) endorse routine annual screening for microalbuminuria (small amounts of albumin in the urine). Once excess albumin excretion is detected, clinicians must employ aggressive CV risk reduction. To optimize outcomes, treatment of microalbuminuria often requires the combined skills of experts in primary care, cardiology, metabolic disease, and nephrology. Although blood pressure reduction usually improves microalbuminuria, agents that block the renin-angiotensin-aldosterone system (RAAS) are most efficacious. Renin-angiotensin-aldosterone system blockers (ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, direct renin inhibitors) may confer CV and kidney advantages in high-risk patients. Their effects on microalbuminuria reduction are greater than those associated with attaining guideline-recommended blood pressure goals. Effective RAAS blockade sometimes induces transient changes in creatinine and potassium, which merit consistent monitoring for the first 2 to 3 months of their use, but rarely necessitate discontinuation. This article also presents an approach to managing increases in creatinine and potassium that should fit comfortably in the hands of primary care clinicians.

  18. Inverse association between serum total bilirubin levels and diabetic peripheral neuropathy in patients with type 2 diabetes.

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    Kim, Eun Sook; Lee, Sung Won; Mo, Eun Young; Moon, Sung Dae; Han, Je Ho

    2015-11-01

    Several studies have suggested that bilirubin, a potent innate antioxidant, plays a protective role against cardiovascular and microvascular disease. This study investigated the association between serum concentrations of total bilirubin (TB) and the presence of diabetic peripheral neuropathy (DPN) in Korean diabetic patients. This cross-sectional study involved 1207 patients aged more than 30 years with type 2 diabetes. DPN was assessed according to clinical symptoms and physical examinations using Michigan Neuropathy Screening Instrument examination score, 10-g monofilament sensation, and current perception threshold. The subjects were stratified into gender-specific tertiles based on TB values, and the relationship between the TB values and DPN was analyzed. Compared with patients within the lowest TB tertile, those with higher TB levels consisted of patients with shorter duration of diabetes, lower HbA1c, better renal function, and less autonomic neuropathy, retinopathy, and albuminuria. Serum TB levels were inversely associated with DPN. In multivariate analysis for the development of DPN after adjusting for potential confounding factors including retinopathy, albuminuria, and autonomic neuropathy, the TB levels were inversely associated with the presence of DPN, both as a continuous variable [odds ratio (OR) per log standard deviation (SD) 0.79; 95% confidence interval (CI) 0.65-0.97; P = 0.022] and when categorized in tertiles (the highest vs. the lowest tertile; OR 0.63; 95% CI 0.40-0.99; P = 0.046). Low serum bilirubin levels are significantly associated with DPN, independently of classic risk factors and other microvascular complications. Further investigation is necessary to determine whether serum bilirubin has a prognostic significance on DPN.

  19. Cubilin is essential for albumin reabsorption in the renal proximal tubule.

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    Amsellem, Sabine; Gburek, Jakub; Hamard, Ghislaine; Nielsen, Rikke; Willnow, Thomas E; Devuyst, Olivier; Nexo, Ebba; Verroust, Pierre J; Christensen, Erik I; Kozyraki, Renata

    2010-11-01

    Receptor-mediated endocytosis is responsible for protein reabsorption in the proximal tubule. This process involves two interacting receptors, megalin and cubilin, which form a complex with amnionless. Whether these proteins function in parallel or as part of an integrated system is not well understood. Here, we report the renal effects of genetic ablation of cubilin, with or without concomitant ablation of megalin, using a conditional Cre-loxP system. We observed that proximal tubule cells did not localize amnionless to the plasma membrane in the absence of cubilin, indicating a mutual dependency of cubilin and amnionless to form a functional membrane receptor complex. The cubilin-amnionless complex mediated internalization of intrinsic factor-vitamin B12 complexes, but megalin considerably increased the uptake. Furthermore, cubilin-deficient mice exhibited markedly decreased uptake of albumin by proximal tubule cells and resultant albuminuria. Inactivation of both megalin and cubilin did not increase albuminuria, indicating that the main role of megalin in albumin reabsorption is to drive the internalization of cubilin-albumin complexes. In contrast, cubulin deficiency did not affect urinary tubular uptake or excretion of vitamin D-binding protein (DBP), which binds cubilin and megalin. In addition, we observed cubilin-independent reabsorption of the "specific" cubilin ligands transferrin, CC16, and apoA-I, suggesting a role for megalin and perhaps other receptors in their reabsorption. In summary, with regard to albumin, cubilin is essential for its reabsorption by proximal tubule cells, and megalin drives internalization of cubilin-albumin complexes. These genetic models will allow further analysis of protein trafficking in the progression of proteinuric renal diseases.

  20. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

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    Huei-Fen Jheng

    2015-10-01

    Full Text Available Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN. Whereas Toll-like receptors (TLRs are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG, induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN.

  1. Alport Syndrome in Women and Girls.

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    Savige, Judy; Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

    2016-09-07

    Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%-30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The "Expert guidelines for the diagnosis and management of Alport syndrome" recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling

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

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    Schanstra, Joost P.; 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 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±−0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD. PMID:25589610

  3. The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio

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    Xiaoyu Ma

    2016-01-01

    Full Text Available Objective. To investigate the expression of miR-192 and its significance in diabetic nephropathy (DN patients. Methods. 464 patients with type 2 diabetes mellitus (T2DM were divided into normal albuminuria group (NA, n=157, microalbuminuria group (MA, n=159, and large amount of albuminuria group (LA, n=148. 127 healthy persons were selected as the control group (NC, n=127. The serum miR-192 levels were detected by Real-Time PCR and transforming growth factor-β1 (TGF-β1 and fibronectin (FN were detected by enzyme-linked immunosorbent assay. The relationships among these parameters were analyzed by Pearson correlation analysis and multiple linear regression analysis. Results. The miR-192 in the LA group was significantly lower than other groups, which was lower in the MA group than in the NA group (P<0.01. The TGF-β1 and FN in the LA group were significantly higher than other groups, which were higher in the MA group than in the NA group (P<0.01. The expression of miR-192 was negatively correlated with TGF-β1, FN, and Ln (UACR and miR-192, TGF-β1, and FN were independent relevant factors affecting Ln (UACR in T2DM (P<0.01. Conclusions. These findings indicate that the levels of miR-192 were lower accompanied by the decrease of urine albumin creatinine ratio (UACR and the association between miR-192 and nephritic fibrosis in DN.

  4. 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.

  5. 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.

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

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    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.

  7. 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.

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

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    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

  9. Effects of calcium channel blockers on proteinuria in patients with diabetic nephropathy.

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    Toto, Robert D; Tian, Min; Fakouhi, Kaffa; Champion, Annette; Bacher, Peter

    2008-10-01

    Diabetic nephropathy management should include the use of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with additional antihypertensive medications to reduce proteinuria and cardiovascular events. Some studies suggest that adding a nondihydropyridine rather than a dihydropyridine calcium channel blocker (CCB) may more effectively lower proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36 weeks. No statistically significant differences were observed between groups in the primary end point; adjusted percentage change in urinary albumin/creatinine ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference, 20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, -0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, -0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be independent of systolic blood pressure reduction in patients who had previously been treated and had baseline blood pressure levels of 142/77 mm Hg.

  10. 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.

  11. Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients.

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    Chen, Szu-chi; Tseng, Chin-Hsiao

    2013-01-01

    This article reviews the relationship between dyslipidemia, chronic kidney disease, and cardiovascular diseases in patients with diabetes. Diabetes mellitus is associated with complications in the cardiovascular and renal system, and is increasing in prevalence worldwide. Modification of the multifactorial risk factors, in particular dyslipidemia, has been suggested to reduce the rates of diabetes-related complications. Dyslipidemia in diabetes is a condition that includes hypertriglyceridemia, low high-density lipoprotein levels, and increased small and dense low-density lipoprotein particles. This condition is associated with higher cardiovascular risk and mortality in diabetic patients. Current treatment guidelines focus on lowering the low-density lipoprotein cholesterol level; multiple trials have confirmed the cardiovascular benefits of treatment with statins. Chronic kidney disease also contributes to dyslipidemia, and dyslipidemia in turn is related to the occurrence and progression of diabetic nephropathy. Different patterns of dyslipidemia are associated with different stages of diabetic nephropathy. Some trials have shown that treatment with statins not only decreased the risk of cardiovascular events, but also delayed the progression of diabetic nephropathy. However, studies using statins as the sole treatment of hyperlipidemia in patients on dialysis have not shown benefits with respect to cardiovascular risk. Diabetic patients with nephropathy have a higher risk of cardiovascular events than those without nephropathy. The degree of albuminuria and the reduction in estimated glomerular filtration rate are also correlated with the risk of cardiovascular events. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to reduce albuminuria in diabetic patients has been shown to decrease the risk of cardiovascular morbidity and mortality.

  12. Apelin retards the progression of diabetic nephropathy.

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    Day, Robert T; Cavaglieri, Rita C; Feliers, Denis

    2013-03-15

    Apelin and its receptor APJ have pleiotropic effects in mice and humans and play a protective role in cardiovascular diseases at least partially by inhibiting oxidative stress. Our objective was to study the effect of apelin on the progression of kidney disease in mice with established type 1 diabetes. Ove26 mice with type 1 diabetes received daily subcutaneous injections of apelin for 2 or 14 wk. APJ localizes in the glomeruli and blood vessels of kidneys. Renal APJ expression was reduced in diabetic mice but increased after treatment with apelin. Apelin treatment did not affect glycemia, body weight, or blood pressure in diabetic mice. Whole kidney and glomerular hypertrophy, as well as renal inflammation, including monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression, NF-κB activation, and monocyte infiltration, was inhibited after short and long treatment with apelin. Apelin administration significantly reduced albuminuria at 6 mo. Short treatment with apelin was sufficient to reverse the downregulation of the antioxidant enzyme catalase. Expression of angiotensin II and angiotensin type 1 receptor (AT1) in kidneys from diabetic mice treated was not affected by apelin. These findings show for the first time that apelin exerts a protective effect on the diabetic kidney. Short administration is sufficient to reduce kidney and glomerular hypertrophy as well as renal inflammation, but prolonged treatment is required to improve albuminuria. This effect was independent of the activation of the renin angiotensin system but correlated with upregulation of the antioxidant catalase. Apelin may represent a novel tool to treat diabetic nephropathy.

  13. 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.

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

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    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.

  15. Prevalence and risk factors of microalbuminuria in Thai nondiabetic hypertensive patients

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    Pongsathorn Gojaseni

    2010-03-01

    Full Text Available Pongsathorn Gojaseni1, Angkana Phaopha1, Worawon Chailimpamontree1, Thaweepong Pajareya1, Anutra Chittinandana21Division of Nephrology, Department of Medicine, Bhumibol Adulyadej Hospital, Directorate of Medical Services, Royal Thai Air Force, Bangkok, Thailand; 2Department of Education, Directorate of Medical Services, Royal Thai Air Force, Bangkok, ThailandPurpose: To assess the prevalence and risk factors of microalbuminuria in nondiabetic hypertensive patients in Thailand.Patients and methods: A cross-sectional study was performed during January to December 2007 at outpatients departments of Bhumibol Adulyadej hospital. Nondiabetic hypertensive patients without a history of pre-existing kidney diseases participated in this study. A questionnaire was used for collecting information on demographics, lifestyle, and family history of cardiovascular and kidney disease. Spot morning urine samples were collected for albuminuria estimation. Albuminuria thresholds were evaluated and defined using albumin-creatinine ratio (ACR.Results: A total of 559 hypertensive patients (283 males, 276 females, aged 58.0 ± 11.6 years were enrolled in this study. Microalbuminuria (ACR 17 to 299 mg/g in males and 25 to 299 mg/g in females was found in 93 cases (16.6% [15.0%‑18.2%]. The independent determinants of elevated urinary albumin excretion in a multiple logistic regression model were; body mass index ≥30 (odds ratio (OR = 2.24, 95% confidence intervals (CI: 1.33–3.76 and dihydropyridine calcium channel blockers (DCCB use (OR = 1.92, 95% CI: 1.22‑3.02.Conclusion: In Thai nondiabetic hypertensive patients, microalbuminuria was not uncommon. Obesity and use of dihydropyridine calcium channel blocker were found to be the important predictors. Prognostic value of the occurrence of microalbuminuria in this population remains to be determined in prospective cohort studies.Keywords: microalbuminuria, hypertension, obesity, calcium channel blocker, metabolic

  16. 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

  17. 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

  18. 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.

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

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    Bedowra Zabeen

    Full Text Available To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII versus multiple daily injections (MDI.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.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.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.

  20. Chronic bilateral renal denervation attenuates renal injury in a transgenic rat model of diabetic nephropathy.

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    Yao, Yimin; Fomison-Nurse, Ingrid C; Harrison, Joanne C; Walker, Robert J; Davis, Gerard; Sammut, Ivan A

    2014-08-01

    Bilateral renal denervation (BRD) has been shown to reduce hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and fibrosis in diabetic nephropathy. This hypothesis was examined in a female streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal denervation resulted in a progressive decrease in systolic blood pressure from first denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and transforming growth factor-β. Renal denervation significantly reduced protein expression of these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the loss of glomerular podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic nephropathy. The evidence presented strongly suggests that renal denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in diabetic nephropathy.

  1. Recent advances in animal models of diabetic nephropathy.

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    Betz, Boris; Conway, Bryan R

    2014-01-01

    Diabetic nephropathy (DN) is the single most common cause of end-stage kidney disease. Therefore, it is imperative that novel therapies are developed. Progress has been hindered, however, by the lack of robust animal models. In the current review we describe recent advances in the field, including the impact of background strain, hypertension and transcriptomic profiling. While the C57BL/6J strain is relatively resistant to DN, the FVB strain appears more susceptible and Ove26 and db/db mice on this background may be useful in modelling types 1 and 2 DN, respectively. Black and tan, brachyury (BTBR) mice deficient for the leptin receptor (ob/ob) develop many of the pathological features of human DN and, remarkably, treatment with exogenous leptin ameliorates hyperglycaemia, albuminuria and glomerulosclerosis. Hypertension plays a key role in the progression of human DN and exacerbates nephropathy in diabetic rodents. Endothelial nitric oxide synthase deficiency (eNOS(-/-)) results in moderate hypertension and the development of nodular glomerulosclerosis and hyaline arteriosclerosis in streptozotocin-induced diabetic C57BL/6J mice. In Cyp1a1mRen2 rats, renin-dependent hypertension synergises with streptozotocin-induced hyperglycaemia to produce a 500-fold increase in albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Renal transcriptional profiling suggests that many of the gene expression changes observed in human DN are replicated in eNOS(-/-) mice and Cyp1a1mRen2 rats. Despite these advances, no model faithfully recapitulates all the features of human DN and further refinements are required. In the interim, it is likely that researchers may use publically available transcriptomic data to select the most appropriate model to study their molecule or pathway of interest.

  2. 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

  3. 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

  4. 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.

  5. 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

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

    Institute of Scientific and Technical Information of China (English)

    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

  7. 硫酸乙酰肝素蛋白多糖基因多态性与糖尿病肾病关系的研究%A study for HSPG gene polymorphism in Chinese type 2 diabetic ne phropathy

    Institute of Scientific and Technical Information of China (English)

    杨涛; 陈家伟; 沈捷

    2001-01-01

    目的探讨硫酸乙酰肝素蛋白多糖基因(HSPG)多态性与中国汉族人2型糖尿病肾脏并发症之间的关系。方法应用限制性内切酶BamHI的PCR-RFLP法,检测190例非DM对照和136例2型糖尿病伴或不伴肾病者的HSP G多态性基因型。结果正常白蛋白尿组和异常(微量和大量)白蛋白尿组之间BamHI HSPG2等位基因频率和基因型频率无显著性差异,非DM对照组和糖尿病组之间B amHI HSPG2等位基因频率无显著性差异,但基因型频率的差异有统计学意义。结论中国汉族人BamHI HSPG2多态性与2型糖尿病肾脏并发症的发生无显著性相关关系,但其基因型频率似与糖尿病发病有关。%Objective To explore the association between th e heparan sulfate proteoglycan gene (HSPG) polymorphism and diabetic nephropathy in Chinese.Methods A case control study of 326 Chinese s ubjects including 136 type 2 diabetics with or without nephropathy and 190 non- diabetic control was performed.Genotype frequencies of HSPG2 polymorphism were s tudied by PCR-RFLP analysis with BamHI digestion.Results There was no difference in genotype frequencies or allele frequencies between normal albuminuria and abnormal albuminuria patients.Moreover,there was no assoc iation between diabetic patients and non-diabetic control in allele frequencies as well,but obvious difference in genotype frequencies(0.05>P>0.025) was found.Conclusion Our study showed the lack of association between HSPG polymorphism and diabetic nephropathy in Chinese type 2 diabetics. There may be association between genotype frequencies of HSPG polymorphism and d iabetes in statistics.

  8. Prevalence of chronic kidney disease and risk factors for its progression: A cross-sectional comparison of Indians living in Indian versus U.S. cities

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    Anand, Shuchi; Kondal, Dimple; Montez-Rath, Maria; Zheng, Yuanchao; Shivashankar, Roopa; Singh, Kalpana; Gupta, Priti; Gupta, Ruby; Ajay, Vamadevan S.; Mohan, Viswanathan; Pradeepa, Rajendra; Tandon, Nikhil; Ali, Mohammed K.; Narayan, K. M. Venkat; Chertow, Glenn M.; Kandula, Namratha; Prabhakaran, Dorairaj; Kanaya, Alka M.

    2017-01-01

    Background While data from the latter part of the twentieth century consistently showed that immigrants to high-income countries faced higher cardio-metabolic risk than their counterparts in low- and middle-income countries, urbanization and associated lifestyle changes may be changing these patterns, even for conditions considered to be advanced manifestations of cardio-metabolic disease (e.g., chronic kidney disease [CKD]). Methods and findings Using cross-sectional data from the Center for cArdiometabolic Risk Reduction in South Asia (CARRS, n = 5294) and Mediators of Atherosclerosis in South Asians Living in America (MASALA, n = 748) studies, we investigated whether prevalence of CKD is similar among Indians living in Indian and U.S. cities. We compared crude, age-, waist-to-height ratio-, and diabetes- adjusted CKD prevalence difference. Among participants identified to have CKD, we compared management of risk factors for its progression. Overall age-adjusted prevalence of CKD was similar in MASALA (14.0% [95% CI 11.8–16.3]) compared with CARRS (10.8% [95% CI 10.0–11.6]). Among men the prevalence difference was low (prevalence difference 1.8 [95% CI -1.6,5.3]) and remained low after adjustment for age, waist-to-height ratio, and diabetes status (-0.4 [-3.2,2.5]). Adjusted prevalence difference was higher among women (prevalence difference 8.9 [4.8,12.9]), but driven entirely by a higher prevalence of albuminuria among women in MASALA. Severity of CKD—-i.e., degree of albuminuria and proportion of participants with reduced glomerular filtration fraction-—was higher in CARRS for both men and women. Fewer participants with CKD in CARRS were effectively treated. 4% of CARRS versus 51% of MASALA participants with CKD had A1c < 7%; and 7% of CARRS versus 59% of MASALA participants blood pressure < 140/90 mmHg. Our analysis applies only to urban populations. Demographic—-particularly educational attainment—-differences among participants in the two

  9. Six cases of hypophosphataemic osteomalacia induced by adefovir dipivoxil%阿德福韦酯致低磷性骨软化症六例分析

    Institute of Scientific and Technical Information of China (English)

    张楠; 邵明玮; 黄爱; 栗夏莲; 秦贵军; 汪丽娟

    2013-01-01

    分析近14个月确诊的6例阿德福韦酯(ADV)相关性肾病患者的临床资料及诊治经过.结果显示,服用ADV 10~20 mg/d,2~3年后出现全身多处骨关节疼痛.均有低磷、低尿酸血症,成骨指标明显升高,1例血肌酐升高,5例有低血钾、肾性糖尿,4例有蛋白尿,影像学检查提示骨质疏松、骨软化、假性骨折.确诊后停用ADV,经补磷及活性D3后,3~6周疼痛缓解,1~2.5个月血尿酸正常,1~2个月肾性糖尿及蛋白尿消失.提示ADV应用超过2年,应注意其引起的肾损害,定期监测肾功能、电解质、尿常规可早期发现肾损害.血尿酸降低是一个较好的诊疗观察指标.%[Summary] An analysis of clinical data was performed in 6 patients diagnosed as adefovir dipivoxil (ADV)-induced nephropathy in recent 14 months.The results showed that all of six patients suffered from pain over multiple joints after taking ADV 10-20 mg/d for 2-3 years,along with hypophosphatemia,hypouricemia,and raised osteogenesis index.One case had increased serum creatinine,5 cases had hypokalemia,renal glycosuria,and4 cases had albuminuria.Imageological examination showed osteoporosis,osteomalacia,and pseudo fracture.After discontinuance of ADV treatment,joint pain was obviously relieved within 3-6 weeks,blood uric acid level returned to normal within 1-2.5 months,and renal glycosuria and albuminuria disappeared by 1-2 months.The results suggest that after taking ADV for more than two years,attention should be paid to the nephropathy induced by ADV and regular monitoring of renal function,blood electrolyte,and urine should be mandatory.Hypouricemia is a reliable index of diagnosis and treatment in this event.

  10. Life expectancy in a large cohort of type 2 diabetes patients treated in primary care (ZODIAC-10.

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    Helen L Lutgers

    Full Text Available BACKGROUND: Most longitudinal studies showed increased relative mortality in individuals with type 2 diabetes mellitus until now. As a result of major changes in treatment regimes over the past years, with more stringent goals for metabolic control and cardiovascular risk management, improvement of life expectancy should be expected. In our study, we aimed to assess present-day life expectancy of type 2 diabetes patients in an ongoing cohort study. METHODOLOGY AND PRINCIPAL FINDINGS: We included 973 primary care type 2 diabetes patients in a prospective cohort study, who were all participating in a shared care project in The Netherlands. Vital status was assessed from May 2001 till May 2007. Main outcome measurement was life expectancy assessed by transforming actual survival time to standardised survival time allowing adjustment for the baseline mortality rate of the general population. At baseline, mean age was 66 years, mean HbA(1c 7.0%. During a median follow-up of 5.4 years, 165 patients died (78 from cardiovascular causes, and 17 patients were lost to follow-up. There were no differences in life expectancy in subjects with type 2 diabetes compared to life expectancy in the general population. In multivariate Cox regression analyses, concentrating on the endpoints 'all-cause' and cardiovascular mortality, a history of cardiovascular disease: hazard ratio (HR 1.71 (95% confidence interval (CI 1.23-2.37, and HR 2.59 (95% CI 1.56-4.28; and albuminuria: HR 1.72 (95% CI 1.26-2.35, and HR 1.83 (95% CI 1.17-2.89, respectively, were significant predictors, whereas smoking, HbA(1c, systolic blood pressure and diabetes duration were not. CONCLUSIONS: This study shows a normal life expectancy in a cohort of subjects with type 2 diabetes patients in primary care when compared to the general population. A history of cardiovascular disease and albuminuria, however, increased the risk of a reduction of life expectancy. These results show that, in a shared

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

    Science.gov (United States)

    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.

  12. 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.

  13. 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.

  14. 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

  15. 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

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

    Science.gov (United States)

    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.

  17. 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.

  18. The use of surrogate endpoints in regulating medicines for cardio-renal disease: opinions of stakeholders.

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    Bauke Schievink

    Full Text Available AIM: There is discussion whether medicines can be authorized on the market based on evidence from surrogate endpoints. We assessed opinions of different stakeholders on this topic. METHODS: We conducted an online questionnaire that targeted various stakeholder groups (regulatory agencies, pharmaceutical industry, academia, relevant public sector organisations and medical specialties (cardiology or nephrology vs. other. Participants were enrolled through purposeful sampling. We inquired for conditions under which surrogate endpoints can be used, the validity of various cardio-renal biomarkers and new approaches for biomarker use. RESULTS: Participants agreed that surrogate endpoints can be used when the surrogate is scientifically valid (5-point Likert response format, mean score: 4.3, SD: 0.9 or when there is an unmet clinical need (mean score: 3.8, SD: 1.2. Industry participants agreed to a greater extent than regulators and academics. However, out of four proposed surrogates (blood pressure (BP, HbA1c, albuminuria, CRP for cardiovascular outcomes or end-stage renal disease, only use of BP for cardiovascular outcomes was deemed moderately accurate (mean: 3.6, SD: 1.1. Specialists in cardiology or nephrology tended to be more positive about the use of surrogate endpoints. CONCLUSION: Stakeholders in drug development do not oppose to the use of surrogate endpoints in drug marketing authorization, but most surrogates are not considered valid. To solve this impasse, increased efforts are required to validate surrogate endpoints and to explore alternative ways to use them.

  19. 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.

  20. Childhood serum sickness: a case report.

    Science.gov (United States)

    Chao, Y K; Shyur, S D; Wu, C Y; Wang, C Y

    2001-09-01

    Childhood serum sickness is a rare allergic disease that follows the administration of a foreign antigenic material, most commonly caused by injecting a protein or haptenic drug. The disease is a type III hypersensitivity reaction mediated by deposits of circulating immune complexes in small vessels, which leads to complement activation and subsequent inflammation. The clinical features are fever, cutaneous eruptions, lymphadenopathy, arthralgias, albuminuria, and nephritis. Serum sickness is an acute self-limited disease. We report a 3-year-old child who presented with fever and a rash; an invasive bacterial infection was strongly suspected. He was therefore given penicillin and gentamicin and responded well. At day 4 after admission, he developed a serum sickness reaction and showed symptoms of arthralgias, generalized edema, purpura, and gross hematuria. The white blood cell count was 12 190/mm3 with 7% eosinophils. Urinalysis revealed red blood cell above 100 per high power field, white blood cell 10 to 15 per high power field, and proteinuria. The antibiotics were discontinued and hydrocortisone (20 mg/kg/d), diphenhydramine HCl (4 mg/kg/d), aspirin (66 mg/kg/d) was administered, plus 1 dose of epinephrine (0.01 mL/kg) administered intramuscularly. On day 7, the 3rd day after withholding antibiotics, his condition dramatically improved. The clinical symptoms resolved progressively and his urinalysis returned to normal.

  1. Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling

    Science.gov (United States)

    Yin, Nanchang; Liu, Wei; Cui, Xiangfei; Chen, Shuo; Wang, Ermin

    2017-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria. Furthermore, the upregulated protein and mRNA expressions of collagen IV and fibronectin in the renal cortices of the db/db mice were inhibited by curcumin treatment. Additionally, curcumin treatment was associated with significant reductions in mature interleukin-1β, cleaved caspase-1, and NLRP3 protein levels in the renal cortices of db/db mice as well as in HK-2 cells exposed to high glucose concentration. In summary, curcumin, a potent antifibrotic agent, is a promising treatment for DN, and its renoprotective effects appear to be mediated by the inhibition of NLRP3 inflammasome activity. PMID:28194406

  2. Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy.

    Science.gov (United States)

    Abouzed, Tarek Kamal; Munesue, Seiichi; Harashima, Ai; Masuo, Yusuke; Kato, Yukio; Khailo, Khaled; Yamamoto, Hiroshi; Yamamoto, Yasuhiko

    2016-01-01

    Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice. Methods. Male mice overexpressing inducible nitric oxide synthase in pancreatic β-cells were employed as a diabetic model. Salicylate (3 g/kg diet) or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day) was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day) was used as a control. Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzyme glyoxalase 1 gene expression were found only in the salicylate treatment group. Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes.

  3. C-peptide and diabetic kidney disease.

    Science.gov (United States)

    Brunskill, N J

    2017-01-01

    Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.

  4. Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice.

    Science.gov (United States)

    Kölling, Malte; Kaucsar, Tamas; Schauerte, Celina; Hübner, Anika; Dettling, Angela; Park, Joon-Keun; Busch, Martin; Wulff, Xaver; Meier, Matthias; Scherf, Kristian; Bukosza, Nóra; Szénási, Gábor; Godó, Mária; Sharma, Amit; Heuser, Michael; Hamar, Peter; Bang, Claudia; Haller, Hermann; Thum, Thomas; Lorenzen, Johan M

    2017-01-04

    Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells. miR-21-mediated repression of Cdc25a and Cdk6 resulted in impaired cell cycle progression and subsequent mesangial cell hypertrophy. miR-21 increased podocyte motility by regulating phosphatase and tensin homolog (Pten). miR-21 antagonism in vitro and in vivo in streptozotocin-induced diabetic mice decreased mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria, and fibrotic- and inflammatory gene expression. In conclusion, miR-21 antagonism rescued various functional and structural parameters in mice with diabetic nephropathy and, thus, might be a viable option in the treatment of patients with diabetic kidney disease.

  5. A new Classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy.

    Science.gov (United States)

    Haneda, Masakazu; Utsunomiya, Kazunori; Koya, Daisuke; Babazono, Tetsuya; Moriya, Tatsumi; Makino, Hirofumi; Kimura, Kenjiro; Suzuki, Yoshiki; Wada, Takashi; Ogawa, Susumu; Inaba, Masaaki; Kanno, Yoshihiko; Shigematsu, Takashi; Masakane, Ikuto; Tsuchiya, Ken; Honda, Keiko; Ichikawa, Kazuko; Shide, Kenichiro

    2015-03-01

    The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts, such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labor and Welfare of Japan. Major revisions to the Classification are summarized as follows: (i) eGFR is substituted for GFR in the Classification; (ii) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (iii) stage 4 (kidney failure) has been redefined as a GFR <30 mL/min/1.73 m(2), regardless of the extent of albuminuria; and (iv) stress has been placed on the differential diagnosis of diabetic nephropathy versus non-diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

  6. Role of Endothelial Nitric Oxide Synthase in Diabetic Nephropathy: Lessons from Diabetic eNOS Knockout Mice

    Directory of Open Access Journals (Sweden)

    Takamune Takahashi

    2014-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in many countries. The animal models that recapitulate human DN undoubtedly facilitate our understanding of this disease and promote the development of new diagnostic markers and therapeutic interventions. Based on the clinical evidence showing the association of eNOS dysfunction with advanced DN, we and others have created diabetic mice that lack eNOS expression and shown that eNOS-deficient diabetic mice exhibit advanced nephropathic changes with distinct features of progressive DN, including pronounced albuminuria, nodular glomerulosclerosis, mesangiolysis, and arteriolar hyalinosis. These studies clearly defined a critical role of eNOS in DN and developed a robust animal model of this disease, which enables us to study the pathogenic mechanisms of progressive DN. Further, recent studies with this animal model have explored the novel mechanisms by which eNOS deficiency causes advanced DN and provided many new insights into the pathogenesis of DN. Therefore, here we summarize the findings obtained with this animal model and discuss the roles of eNOS in DN, unresolved issues, and future investigations of this animal model study.

  7. Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy

    Science.gov (United States)

    Xu, Longquan; Hiller, Sylvia; Simington, Stephen; Nickeleit, Volker; Maeda, Nobuyo; James, Leighton R.; Yi, Xianwen

    2016-01-01

    Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model with over- or under-expression of lipoic acid synthase gene (Lias). These models have been mated with Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic changes and oxidative stress status in two new strains of the mice with controls. Our results show that Ins2Akita/+ mice with under-expressed Lias gene, exhibit higher oxidative stress and more severe DN features (albuminuria, glomerular basement membrane thickening and mesangial matrix expansion). In contrast, Ins2Akita/+ mice with highly-expressed Lias gene display lower oxidative stress and less DN pathologic changes. Our study demonstrates that strengthening endogenous antioxidant capacity could be an effective strategy for prevention and treatment of DN. PMID:27706190

  8. 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.

  9. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers.

    Science.gov (United States)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik; Navis, Gerjan J; Lewis, Julia B; Ritz, Eberhard; de Graeff, Pieter A; de Zeeuw, Dick

    2012-08-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi-based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus, treatment effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving ARB therapy.

  10. SGLT-2 inhibition in patients with kidney disease.

    Science.gov (United States)

    Gilbert, R E

    2014-12-01

    Accustomed to managing diabetes with agents that mostly act by modulating the secretion and actions of insulin, with the advent of sodium-glucose linked transporter-2 (SGLT-2) inhibitors, physicians are now aware that the kidney also needs to be considered in the spectrum of action of anti-hyperglycaemic agents. Though familiar with the need for dose adjustment when prescribing many of our current anti-hyperglycaemic drugs in the setting of kidney dysfunction, with the SGLT-2 inhibitors pharmacodynamic as well as pharmacokinetic aspects also need to be considered. Finally, through their ability to reduce intraglomerular pressure, systemic blood pressure and plasma uric acid concentration, the SGLT-2 inhibitors offers the possibility of kidney protection. An hypothesis that will need to be tested with long term studies that address changes in the kidney beyond albuminuria, assessing the rate of decline in glomerular filtration rate and 'hard'kidneyrelated endpoints such as the need for renal replacement therapy (dialysis, transplantation) will be important in this setting.

  11. Reversal of diabetic nephropathy by a ketogenic diet.

    Directory of Open Access Journals (Sweden)

    Michal M Poplawski

    Full Text Available Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita and Type 2 (db/db diabetes, diabetic nephropathy (as indicated by albuminuria was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.

  12. Growth hormone (GH)-transgenic insulin-like growth factor 1 (IGF1)-deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth.

    Science.gov (United States)

    Blutke, Andreas; Schneider, Marlon R; Wolf, Eckhard; Wanke, Rüdiger

    2016-03-01

    Growth hormone (GH)-transgenic mice with permanently elevated systemic levels of GH and insulin-like growth factor 1 (IGF1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF1-dependent and -independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF1-deficient (I(-/-)) and of IGF1-deficient GH-transgenic mice (I(-/-)/G), as well as of GH-transgenic (G) and nontransgenic wild-type control mice (I(+/+)) were examined by quantitative stereological and functional analyses. Both G and I(-/-)/G mice developed glomerular hypertrophy, hyperplasia of glomerular mesangial and endothelial cells, podocyte hypertrophy and foot process effacement, albuminuria, and glomerulosclerosis. However, I(-/-)/G mice exhibited less severe glomerular alterations, as compared to G mice. Compared to I(+/+) mice, G mice exhibited renal hypertrophy with a significant increase in the number without a change in the size of proximal tubular epithelial (PTE) cells. In contrast, I(-/-)/G mice did not display significant PTE cell hyperplasia, as compared to I(-/-) mice. These findings indicate that GH excess stimulates glomerular growth and induces lesions progressing to glomerulosclerosis in the absence of IGF1. In contrast, IGF1 represents an important mediator of GH-dependent proximal tubular growth in GH-transgenic mice.

  13. 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

  14. 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

  15. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion

    Science.gov (United States)

    Fan, Xueping; Yang, Hongying; Kumar, Sudhir; Tumelty, Kathleen E.; Pisarek-Horowitz, Anna; Sharma, Richa; Chan, Stefanie; Tyminski, Edyta; Shamashkin, Michael; Belghasem, Mostafa; Henderson, Joel M.; Coyle, Anthony J.; Berasi, Stephen P.

    2016-01-01

    The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development and podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating podocyte function is not known. Here we report that a potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with ROBO2/SRGAP1/NMIIA in the presence of SLIT2. Immunostaining demonstrated that SRGAP1 is a podocyte protein and is colocalized with ROBO2 on the basal surface of podocytes. In addition, SLIT2 stimulation inhibits NMIIA activity, decreases focal adhesion formation, and reduces podocyte attachment to collagen. In vivo studies further showed that podocyte-specific knockout of Robo2 protects mice from hypertension-induced podocyte detachment and albuminuria and also partially rescues the podocyte-loss phenotype in Myh9 knockout mice. Thus, we have identified SLIT2/ROBO2/SRGAP1/NMIIA as a potentially novel signaling pathway in kidney podocytes, which may play a role in regulating podocyte adhesion and attachment. Our findings also suggest that SLIT2/ROBO2 signaling might be a therapeutic target for kidney diseases associated with podocyte detachment and loss. PMID:27882344

  16. The Prognosis of Patients with Chronic Kidney Disease and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    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.

  17. [The role of the diet as a risk factor for the development and progression of diabetic nephropathy].

    Science.gov (United States)

    Mello, Vanessa D F de; Azevedo, Mirela J de; Zelmanovitz, Themis; Gross, Jorge L

    2005-08-01

    Diabetic nephropathy (DN) is the leading cause of kidney disease in patients starting renal replacement therapy, and affects up to 40% of type 1 and type 2 diabetic patients. Diet seems to play an important role in the development of the disease. There are evidences supporting the concept that not only the amount but also the origin of dietary protein are associated with DN. Few studies analyzed the role of dietary lipids. A low-protein diet slows down the decline of renal function and ameliorates the DN prognosis and death in patients with type 1 diabetes with micro- and macroalbuminuria. Studies in type 2 diabetic patients are scanty but short-term studies suggest that this approach decreases albuminuria. However, the use of low-protein diet for long periods is compromised by poor compliance and its long-term safety is not firmly established. Enthusiastic results come up when comparing the effect of different sources of animal protein on renal function and lipid profile in patients with DN, which may represent an alternative strategy for low-protein diet on medical nutritional therapy in patients with DN and in cardiovascular risk factors and endothelial function.

  18. Stromal cell-derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy.

    Science.gov (United States)

    Takashima, Satoru; Fujita, Hiroki; Fujishima, Hiromi; Shimizu, Tatsunori; Sato, Takehiro; Morii, Tsukasa; Tsukiyama, Katsushi; Narita, Takuma; Takahashi, Takamune; Drucker, Daniel J; Seino, Yutaka; Yamada, Yuichiro

    2016-10-01

    The role of stromal cell-derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice. The DPP-4 inhibitor linagliptin, but not the GLP-1R agonist liraglutide, further augmented renal SDF-1 expression in both Glp1r(+/+) and Glp1r(-/-) diabetic-prone mice. Along with upregulation of renal SDF-1 expression, the progression of albuminuria, glomerulosclerosis, periglomerular fibrosis, podocyte loss, and renal oxidative stress was suppressed in linagliptin-treated Glp1r(+/+) diabetic-prone mice. Linagliptin treatment increased urinary sodium excretion and attenuated the increase in glomerular filtration rate which reflects glomerular hypertension and hyperfiltration. In contrast, selective SDF-1 receptor blockade with AMD3100 reduced urinary sodium excretion and aggravated glomerular hypertension in the Glp1r(+/+) diabetic-prone mice. Thus, DPP-4 inhibition, independent of GLP-1R signaling, contributes to protection of the diabetic kidney through SDF-1-dependent antioxidative and antifibrotic effects and amelioration of adverse renal hemodynamics.

  19. Global renal gene expression profiling analysis in B2-kinin receptor null mice: impact of diabetes.

    Directory of Open Access Journals (Sweden)

    Miran A Jaffa

    Full Text Available Diabetic nephropathy (DN, the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The risk factors and mechanisms that contribute to the development and progression of DN are still incompletely defined. To address the involvement of bradykinin B(2-receptors (B(2R in DN, we used a genome wide approach to study the effects of diabetes on differential renal gene expression profile in wild type and B(2R knockout (B(2R(-/- mice. Diabetes was induced with streptozotocin and plasma glucose levels and albumin excretion rate (AER were measured at predetermined times throughout the 23 week study period. Longitudinal analysis of AER indicated that diabetic B(2R(-/-D null mice had a significantly decreased AER levels compared to wild type B(2R(+/+D mice (P = 0.0005. Results from the global microarray study comparing gene expression profiles among four groups of mice respectively: (B(2R(+/+C, B(2R(+/+D, B(2R(-/-C and B(2R(-/-D highlighted the role of several altered pathological pathways in response to disruption of B(2R and to the diabetic state that included: endothelial injury, oxidative stress, insulin and lipid metabolism and inflammatory process with a marked alteration in the pro-apoptotic genes. The findings of the present study provide a global genomics view of biomarkers that highlight the mechanisms and putative pathways involved in DN.

  20. Urinary Analysis of Fluid Retention in the General Population: A Cross-Sectional Study

    Science.gov (United States)

    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

  1. Urinary retinol binding protein is a marker of the extent of interstitial kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    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.

  2. The effect of liraglutide on renal function

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Persson, Frederik; Rosenlund, Signe;

    2017-01-01

    (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. MATERIALS AND METHODS: Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin......-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m(2) . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER). RESULTS: A total of 32 patients were......) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m(2) ( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm...

  3. Risk factor control is key in diabetic nephropathy.

    Science.gov (United States)

    Lewis, Gareth; Maxwell, Alexander P

    2014-02-01

    Prolonged duration of diabetes, poor glycaemic control and hypertension are major risk factors for both diabetic nephropathy and cardiovascular disease. Optimising blood sugar control together with excellent control of blood pressure can reduce the risk of developing diabetic nephropathy. Diabetic nephropathy should be considered in any patient with diabetes when persistent albuminuria develops. Microalbuminuria is the earliest clinically detectable indicator of diabetic nephropathy risk. The majority of patients with diabetic nephropathy are appropriately diagnosed based on elevated urinary albumin excretion and/or reduced 0032-6518 renal function. Patients with type 2 diabetes should have annual urinary ACR measurements from the time of diabetes diagnosis while those with type 1 diabetes should commence five years after diagnosis. Blood pressure lowering to 130/80mmHg and reduction of proteinuria to diabetic nephropathy and reduces the number of cardiovascular events. Drugs that block the renin-angiotensin-aldosterone system (RAAS) are effective in reducing proteinuria, managing hypertension and reducing cardiovascular risk. Unless there are clear contraindications or intolerance all patients with diabetic nephropathy should be prescribed an ACEI or ARB. Stopping an ACEI or ARB during intercurrent illness or times of volume depletion is critically important. Patients with diabetic nephropathy should have at least yearly measurements of blood pressure, renal function and urinary ACR.

  4. A new classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy.

    Science.gov (United States)

    Haneda, Masakazu; Utsunomiya, Kazunori; Koya, Daisuke; Babazono, Tetsuya; Moriya, Tatsumi; Makino, Hirofumi; Kimura, Kenjiro; Suzuki, Yoshiki; Wada, Takashi; Ogawa, Susumu; Inaba, Masaaki; Kanno, Yoshihiko; Shigematsu, Takashi; Masakane, Ikuto; Tsuchiya, Ken; Honda, Keiko; Ichikawa, Kazuko; Shide, Kenichiro

    2015-02-01

    The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease. In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labour and Welfare of Japan. Major revisions to the Classification are summarized as follows: (1) eGFR is substituted for GFR in the Classification; (2) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (3) stage 4 (kidney failure) has been redefined as a GFR less than 30 mL/min/1.73 m(2), regardless of the extent of albuminuria; and (4) stress has been placed on the differential diagnosis of diabetic nephropathy versus non-diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

  5. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi

    2016-01-01

    Full Text Available 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.

  6. 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.

  7. 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.

  8. Relationship between serum indicators, endothelial injury markers and renal damage in patients with ANCA-associated systemic vasculitis

    Institute of Scientific and Technical Information of China (English)

    Wei-Jia Liu; Jun-Bo Huang

    2016-01-01

    Objective:To study the relationship between serum indicators, endothelial injury markers and renal damage in patients with ANCA-associated systemic vasculitis.Methods:Patients with ANCA-associated systemic vasculitis were selected for study, 30 cases of patients not complicated with renal damage were screened as AAV group and 30 cases of patients complicated with renal damage were screened as renal damage group, and then serum autoantibody contents and endothelial injury marker contents were detected.Results:Serum PR3-ANCA and MPO-ANCA contents of renal damage group were not statistically different from those of AAV group while anti-LAMP-2 antibody and AECA contents were significantly higher than those of AAV group; serum CECs, vWF, ES and VCAM-1 contents of renal damage group were significantly higher than those of AAV group while TM and eNOS contents were lower than those of AAV group; the higher the CKD stage in renal damage group, the more significant the albuminuria, the higher the serum CECs, vWF, ES and VCAM-1 contents and the lower the TM and eNOS contents.Conclusion:Abnormal contents of serum autoantibody anti-LAMP-2 antibody, AECA and endothelial injury markers in patients with ANCA-associated systemic vasculitis are closely related to renal damage and can be used for disease evaluation.

  9. Prevalence of Chronic Kidney Disease among Patients Attending a Specialist Diabetes Clinic in Jamaica

    Science.gov (United States)

    Ferguson, TS; Tulloch-Reid, MK; Younger-Coleman, NO; Wright-Pascoe, RA; Boyne, MS; Soyibo, AK; Wilks, RJ

    2015-01-01

    ABSTRACT Objectives: To estimate the prevalence of chronic kidney disease (CKD) among patients attending the University Hospital of the West Indies (UHWI) Diabetes Clinic and to determine the proportion of patients at high risk for adverse outcomes. Methods: We conducted a cross-sectional study among patients attending the UHWI Diabetes Clinic between 2009 and 2010. Trained nurses administered a questionnaire, reviewed dockets, and performed urinalyses. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Albuminuria was assessed using urine test strips for protein and microalbumin. Chronic kidney disease was defined as an eGFR 300 mg/g) in 62.1%. Overall prevalence of CKD was 86.3% (95% CI 80.4%, 92.2%). Based on KDIGO risk categories, 50.8% were at high risk and 17.4% at very high risk of adverse outcomes. Conclusion: Most patients at the UHWI Diabetes Clinic had CKD and were at high or very high risk of adverse outcomes. Further studies to determine the burden of CKD in other clinical settings and to identify the best strategies for preventing adverse outcomes in developing countries need to be conducted. PMID:26426170

  10. Hypertension in pregnancy is a risk factor for microalbuminuria later in life.

    Science.gov (United States)

    Kattah, Andrea G; Asad, Reem; Scantlebury, Dawn C; Bailey, Kent R; Wiste, Heather J; Hunt, Steven C; Mosley, Thomas H; Kardia, Sharon L R; Turner, Stephen T; Garovic, Vesna D

    2013-09-01

    The authors aimed to compare renal function by estimated glomerular filtration rate and albuminuria in 3 groups of women: nulliparous women, women with a history of normotensive pregnancies, and women with a history of at least one hypertensive pregnancy. Women who participated in the second Family Blood Pressure Program Study visit (2000-2004) and had serum creatinine and urine albumin measurements (n=3015) were categorized as having had no pregnancy lasting >6 months (n=341), having had only normotensive pregnancies (n=2199), or having had at least 1 pregnancy with hypertension (n=475) based on a standardized questionnaire. Women who reported having had at least one pregnancy with hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%, Ppregnancies. There was a significantly greater risk of microalbuminuria (urine albumin-creatinine ratio >25 mg/g) in those who reported at least one pregnancy with hypertension (odds ratio, 1.37; confidence interval, 1.02-1.85; P=.04) than in those with normotensive pregnancies, after adjusting for risk factors for chronic kidney and cardiovascular disease. Hypertension in pregnancy is associated with an increased risk of future microalbuminuria.

  11. 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.

  12. 17β Estradiol Modulates Perfusion Pressure and Expression of 5-LOX and CYP450 4A in the Isolated Kidney of Metabolic Syndrome Female Rats

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    A. M. Zúñiga-Muñoz

    2015-01-01

    Full Text Available Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF-α were increased in ovariectomized metabolic syndrome rats (p<0.001. The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 μg of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways.

  13. 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.

  14. Advances in Renal Sympathetic Denervation%肾脏交感神经射频消融术临床效应研究进展

    Institute of Scientific and Technical Information of China (English)

    肖宜超

    2012-01-01

    Renal sympathetic denervation (RSD) is a novel catheter-based approach to directly target renal sympathetic nerves using radiofrequency ablation technology, which can suppress the activation of the sympathetic nervous system. It has been indicated that RSD can not only significantly lower peripheral blood pressure in patients with resistant hypertension, but shows improvement in left ventricular hypertrophy , heart failure, insulin resistance and albuminuria. This review focuses on the clinical effects of renal sympathetic denervation and the prospects of its clinical application.%肾脏交感神经射频消融术是一种新型的、选择性降低肾脏交感神经活性的介入治疗手段,最新研究证实不仅可显著降低顽固性高血压患者血压水平,而且临床研究发现还具有逆转左心室肥厚、改善心功能、改善胰岛素抵抗、降低尿蛋白等临床效应;现主要对肾脏交感神经射频消融术的临床效应及应用前景进行综述.

  15. Early detection of diabetic kidney disease: Present limitations and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Chih-Hung; Lin; Yi-Cheng; Chang; Lee-Ming; Chuang

    2016-01-01

    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(eG FR) 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 eG FR 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.

  16. 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.

  17. Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    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.

  18. Acute endotoxemia in mice induces downregulation of megalin and cubilin in the kidney.

    Science.gov (United States)

    Schreiber, Andrea; Theilig, Franziska; Schweda, Frank; Höcherl, Klaus

    2012-07-01

    Severe sepsis is often accompanied by acute renal failure with renal tubular dysfunction. Albuminuria is a common finding in septic patients and we studied whether it was due to an impairment of proximal tubular endocytosis of filtered albumin. We studied the regulation of megalin and cubilin, the two critical multiligand receptors responsible for albumin absorption, during severe experimental endotoxemia. Lipopolysaccharide (LPS) caused a time- and dose-dependent suppression of megalin and cubilin expression that was paralleled by a decrease in plasma albumin levels and an increase in the urine concentration of albumin in mice. Incubation of rat renal cortical slices with LPS also reduced the mRNA expression of megalin and cubilin. Further, LPS suppressed megalin and cubilin mRNA expression in murine primary proximal tubule cells and decreased the uptake of FITC albumin in these cells. In addition, the increase in urine levels of albumin in response to ischemia/reperfusion-induced acute renal failure was paralleled by a decrease in the expression of megalin and cubilin. Thus, our data indicate that the expression of megalin and cubilin is decreased during experimental endotoxemia and in response to renal ischemia/reperfusion injury. This downregulation may contribute, in part, to an increase in urine levels of albumin during acute renal failure.

  19. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    Science.gov (United States)

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  20. Renoprotective Effects of Combining ACE Inhibitors and Statins in Experimental Diabetic Rats

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    NC. Nagalakshmi

    2011-12-01

    Full Text Available Background and the purpose of the study: The combination of angiotensin II receptor antagonists and HMG CoA reductase inhibitors have shown to confer renoprotection.The purpose of this study was to find out the renoprotective effects of telmisartan and atorvastatin in combination and in monotherapy of Streptozotocin (STZ induced diabetic nephropathy in rats. Methods: Diabetes was induced by i.p injection of STZ to rats, after 18 hrs of fasting. Diabetic rats were randomly grouped and treated with telmisartan and atorvastatin in combination as well as monotherapy for 30 days. The serum and urine glucose, creatinine and serum triglyceride, cholesterol, albumin and micro-albumin and blood urea nitrogen, total protein and histological analyses of the left kidney were performed at the end of the study. Results: By the end of the study, the combination showed significant (P < 0.05 improvement in urine glucose, serum cholesterol, serum and urine creatinine, blood urea nitrogen, total protein, serum albumin, micro-albuminuria levels in comparison to monotherapy. However, this combination didn't show significant changes on serum glucose and triglyceride levels. Kidney pathological injury was attenuated by the combination as compared to the diabetic group. Conclusion: The present study document that, telmisartan and atorvastatin combination have better renoprotective effects but not with individual drug when compared to the diabetic group. The combination also attenuated the progression of diabetic nephropathy by slowing the proteinuria and microalbuminuria and these effects were confirmed by histopathological analysis.

  1. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans.

    Science.gov (United States)

    Spencer, Andrew G; Labonte, Eric D; Rosenbaum, David P; Plato, Craig F; Carreras, Christopher W; Leadbetter, Michael R; Kozuka, Kenji; Kohler, Jill; Koo-McCoy, Samantha; He, Limin; Bell, Noah; Tabora, Jocelyn; Joly, Kristin M; Navre, Marc; Jacobs, Jeffrey W; Charmot, Dominique

    2014-03-12

    The management of sodium intake is clinically important in many disease states including heart failure, kidney disease, and hypertension. Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3, which plays a prominent role in sodium handling in the gastrointestinal tract and kidney. When administered orally to rats, tenapanor acted exclusively in the gastrointestinal tract to inhibit sodium uptake. We showed that the systemic availability of tenapanor was negligible through plasma pharmacokinetic studies, as well as autoradiography and mass balance studies performed with (14)C-tenapanor. In humans, tenapanor reduced urinary sodium excretion by 20 to 50 mmol/day and led to an increase of similar magnitude in stool sodium. In salt-fed nephrectomized rats exhibiting hypervolemia, cardiac hypertrophy, and arterial stiffening, tenapanor reduced extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in a dose-dependent fashion. We observed these effects whether tenapanor was administered prophylactically or after disease was established. In addition, the combination of tenapanor and the blood pressure medication enalapril improved cardiac diastolic dysfunction and arterial pulse wave velocity relative to enalapril monotherapy in this animal model. Tenapanor prevented increases in glomerular area and urinary KIM-1, a marker of renal injury. The results suggest that therapeutic alteration of sodium transport in the gastrointestinal tract instead of the kidney--the target of current drugs--could lead to improved sodium management in renal disease.

  2. Activation of thiazide-sensitive co-transport by angiotensin II in the cyp1a1-Ren2 hypertensive rat.

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    Ali Ashek

    Full Text Available Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage. Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ≈ 20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.

  3. Effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats.

    Science.gov (United States)

    Ibrahim, Doaa S; Abd El-Maksoud, Marwa A E

    2015-04-01

    Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension and progressive renal insufficiency. The aim of this study was to investigate the effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats. Streptozotocin (STZ) diabetic rats were orally treated with three doses (50, 100 and 200 mg/kg) of strawberry leaf extract for 30 days. Nephropathy biomarkers in plasma and kidney were examined at the end of the experiment. The three doses of strawberry leaf extract significantly decreased the levels of blood glucose, urea nitrogen, plasma creatinine, kidney injury molecule (Kim)-1, renal malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), interleukin (IL)- 6 and caspase-3 in diabetic rats. Meanwhile, the levels of plasma insulin, albumin, uric acid, renal catalase (CAT), superoxide dismutase (SOD) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in diabetic rats treated with strawberry leaf extract. These results indicate the role of strawberry leaves extract as anti-diabetic, antioxidant, anti-inflammatory and anti-apoptosis in diabetic nephropathy.

  4. 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...... determined once weekly. After three weeks, animals were sacrificed. Heart tissue was examined for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) by RT-PCR. RESULTS: The vitamin D depleted group had higher blood pressure at week 1 (mean difference 23.4mmHg, 95% CI 9.1-37.7) and tended...... to have higher blood pressure in weeks 2 and 3 (mean difference 14.3mmHg 95% CI -0.02-28.7 and 15.2mmHg 95% CI -1.5-33). The depletion group had higher heart-to-body weight ratio, and a trend towards higher ANP and BNP levels. The group receiving paricalcitol did not perform better. No differences were...

  5. A novel mouse model of advanced diabetic kidney disease.

    Directory of Open Access Journals (Sweden)

    Jean-Francois Thibodeau

    Full Text Available Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice. Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen were employed as a model of angiotensin-dependent hypertension. Diabetes was induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice or by intercrossing with OVE26 diabetic mice (HD-OVE mice. Both HD-STZ and HD-OVE mice displayed more pronounced increases in urinary albumin levels as compared with their diabetic littermates. Additionally, HD mice displayed renal hypertrophy, advanced glomerular scarring and evidence of tubulointerstitial fibrosis. Both HD-OVE and HD-STZ mice showed evidence of GFR decline as FITC-inulin clearance was decreased compared to hyperfiltering STZ and OVE mice. Taken together our results suggest that HD mice represent a robust model of type I DN that recapitulates key features of human disease which may be significant in studying the pathogenesis of DN and in the assessment of putative therapeutics.

  6. 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.

  7. Arsenic-mediated nephrotoxicity.

    Science.gov (United States)

    Robles-Osorio, Ma Ludivina; Sabath-Silva, Elizabeth; Sabath, Ernesto

    2015-05-01

    Chronic kidney disease (CKD) is an important global health problem that affects 8-15% of the population according to epidemiological studies done in different countries. Essential to prevention is the knowledge of the environmental factors associated with this disease, and heavy metals such as lead and cadmium are clearly associated with kidney injury and CKD progression. Arsenic is one of the most abundant contaminants in water and soil, and many epidemiological studies have found an association between arsenic and type 2 diabetes mellitus, hypertension and cancer; however, there is a scarcity of epidemiological studies about its association with kidney disease, and the evidence linking urinary arsenic excretion with CKD, higher urinary excretion of low molecular proteins, albuminuria or other markers of renal in injury is still limited, and more studies are necessary to characterize the role of arsenic on renal injury and CKD progression. Global efforts to reduce arsenic exposure remain important and research is also needed to determine whether specific therapies are beneficial in susceptible populations.

  8. Intermedin ameliorates IgA nephropathy by inhibition of oxidative stress and inflammation.

    Science.gov (United States)

    Wang, Yanhong; Tian, Jihua; Guo, Haixiu; Mi, Yang; Zhang, Ruijing; Li, Rongshan

    2016-05-01

    IgA nephropathy (IgAN) is the most frequent form of glomerulonephritis worldwide. The role of oxidative stress and inflammation in the pathogenesis of IgAN has been reported. Intermedin (IMD) is a newly discovered peptide that is closely related to adrenomedullin. We have recently reported that IMD can significantly reduce renal ischemia/reperfusion injury by diminishing oxidative stress and suppressing inflammation. The present study was designed to explore whether IMD ameliorates IgAN via oxidative stress- and inflammation-dependent mechanisms. Our results showed that IMD administration resulted in the prevention of albuminuria and ameliorated renal pathomorphological changes. These findings were associated with (1) decreased renal TGF-β1 and collagen IV expression, (2) an increased SOD level and reduced MDA level, (3) the inhibition of the renal activation of NF-κB p65 and (4) the downregulation of the expression of inflammatory factors (TNF-α, MCP-1 and MMP-9) in the kidney. These results indicate that IMD in the kidney protects against IgAN by reducing oxidative stress and suppressing inflammation.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. [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).

  14. COPD and microalbuminuria: a 12-year follow-up study.

    Science.gov (United States)

    Romundstad, Solfrid; Naustdal, Thor; Romundstad, Pål Richard; Sorger, Hanne; Langhammer, Arnulf

    2014-04-01

    Chronic obstructive pulmonary disease (COPD), low lung function independent of diagnosis and markers of inflammation are all associated with increased morbidity and mortality. Microalbuminuria, reflecting endothelial dysfunction, could be a relevant inflammatory marker of potential systemic effects of COPD. We hypothesised that there was a positive association between microalbuminuria and mortality in individuals with COPD. We conducted a 12-year follow-up study of 3129 participants in the second survey of the Nord-Trøndelag Health Study (HUNT), Norway. At baseline, albuminuria was analysed in three urine samples and spirometry was performed. Among the participants, 136 had COPD and microalbuminuria, defined as a urinary albumin/creatinine ratio between 2.5 and 30.0 mg·mmol(-1). The main outcome measures were hazard ratio of all-cause mortality according to microalbuminuria. Compared to those with COPD without microalbuminuria, the adjusted hazard ratio for all-cause mortality in those with COPD and microalbuminuria was 1.54, 95% CI 1.16-2.04. This result was similar after excluding cardiovascular disease at baseline. Classifying COPD severity by Global Initiative for Chronic Obstructive Lung Disease, there was a positive association trend with increasing severity stages. Microalbuminuria is associated with all-cause mortality in individuals with COPD and could be a relevant tool in identification of patients with poor prognosis.

  15. New-onset microalbuminuria following allogeneic myeloablative SCT is a sign of near-term decrease in renal function.

    Science.gov (United States)

    Morito, T; Ando, M; Kobayashi, T; Kakihana, K; Ohashi, K; Akiyama, H; Tsuchiya, K; Nitta, K; Sakamaki, H

    2013-07-01

    The emergence of microalbuminuria following conditioning chemotherapy may predict the development of renal dysfunction. To confirm this, a 1-year retrospective cohort study was conducted in 31 myeloablative allogeneic SCT patients who received five consecutive measurements of albuminuria before conditioning therapy and on days 0, 7, 14 and 28 following SCT. The cohort had neither microalbuminuria nor renal dysfunction at baseline. Microalbuminuria was defined as an albumin-creatinine (Cr) ratio over 30 mg/g, and renal dysfunction was as an estimated glomerular filtration rate microalbuminuria with the incidence of renal dysfunction. In all, 16 patients (52%) developed microalbuminuria that was positive at least two times among the four measurements after SCT. The actuarial occurrence of chronic kidney disease was significantly higher in patients who developed microalbuminuria than in those who did not. Incidence of microalbuminuria had a significant risk of subsequent renal dysfunction (hazard ratio (95% confidence interval), 7.3 (1.2-140)). In conclusion, de novo microalbuminuria following conditioning therapy is a warning of near-term loss of renal function.

  16. The association between glycemic control and microalbuminuria in Type 2 diabetes.

    Science.gov (United States)

    Showail, Anwar Ali; Ghoraba, Medhat

    2016-05-01

    Microalbuminuria is an independent risk factor for cardiovascular and renal out- come in a patient with Type 2 diabetes. The evidence that intensive glycemic control reduces the microvascular complications of diabetes is based almost exclusively on prevention of micro- albuminuria. To evaluate the association between microalbuminuria and glycemic control and other factors in Type 2 diabetes, we studied retrospectively 551 patients with Type 2 diabetes. The patients were divided into two groups: 175 patients with microalbuminuria in the case group and 376 with normal urine albumin-creatinine ratio in the control group. Our data indicated that there was a significant association between the uncontrolled glycemia and development of microalbuminuria and that was more obvious if HbA1c level was >11%. Our data also indicate that there was a statistical significant association between male gender, age, the systolic and diastolic blood pressure (DBP) levels, and the microalbuminuria in crude odds ratios (ORs). We conclude that there was a clear association between the glycemic control and microalbuminuria, and microalbuminuria was associated with older age, male gender, and systolic and DBP in crude ORs.

  17. Astragaloside IV ameliorates renal injury in db/db mice

    Science.gov (United States)

    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.

  18. Establishment of mouse model of MYH9 disorders: heterozygous R702C mutation provokes macrothrombocytopenia with leukocyte inclusion bodies, renal glomerulosclerosis and hearing disability.

    Science.gov (United States)

    Suzuki, Nobuaki; Kunishima, Shinji; Ikejiri, Makoto; Maruyama, Shoichi; Sone, Michihiko; Takagi, Akira; Ikawa, Masahito; Okabe, Masaru; Kojima, Tetsuhito; Saito, Hidehiko; Naoe, Tomoki; Matsushita, Tadashi

    2013-01-01

    Nonmuscle myosin heavy chain IIA (NMMHCIIA) encoded by MYH9 is associated with autosomal dominantly inherited diseases called MYH9 disorders. MYH9 disorders are characterized by macrothrombocytopenia and very characteristic inclusion bodies in granulocytes. MYH9 disorders frequently cause nephritis, sensorineural hearing disability and cataracts. One of the most common and deleterious mutations causing these disorders is the R702C missense mutation. We generated knock-in mice expressing the Myh9 R702C mutation. R702C knock-in hetero mice (R702C+/- mice) showed macrothrombocytopenia. We studied megakaryopoiesis of cultured fetal liver cells of R702C+/- mice and found that proplatelet formation was impaired: the number of proplatelet tips was decreased, proplatelet size was increased, and proplatelet shafts were short and enlarged. Although granulocyte inclusion bodies were not visible by May-Grünwald Giemsa staining, immunofluorescence analysis indicated that NMMHCIIA proteins aggregated and accumulated in the granulocyte cytoplasm. In other organs, R702C+/- mice displayed albuminuria which increased with age. Renal pathology examination revealed glomerulosclerosis. Sensory hearing loss was indicated by lowered auditory brainstem response. These findings indicate that Myh9 R702C knock-in mice mirror features of human MYH9 disorders arising from the R702C mutation.

  19. [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.

  20. 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.

  1. Impact of emerging health insurance arrangements on diabetes outcomes and disparities: rationale and study design.

    Science.gov (United States)

    Wharam, J Frank; Soumerai, Steve; Trinacty, Connie; Eggleston, Emma; Zhang, Fang; LeCates, Robert; Canning, Claire; Ross-Degnan, Dennis

    2013-01-01

    Consumer-directed health plans combine lower premiums with high annual deductibles, Internet-based quality-of-care information, and health savings mechanisms. These plans may encourage members to seek better value for health expenditures but may also decrease essential care. The expansion of high-deductible health plans (HDHPs) represents a natural experiment of tremendous proportion. We designed a pre-post, longitudinal, quasi-experimental study to determine the effect of HDHPs on diabetes quality of care, outcomes, and disparities. We will use a 13-year rolling sample (2001-2013) of members of an HDHP and members of a control group. To reduce selection bias, we will limit participants to those whose employers mandate a single health insurance type. The study will measure rates of monthly hemoglobin A1c, lipid, and albuminuria testing; availability of blood glucose test strips; and rates of retinal examinations, high-severity emergency department visits, and preventable hospitalizations. Results could be used to design health plan features that promote high-quality care and better outcomes among people who have diabetes.

  2. Focal segmental glomerulosclerosis lagged behind the onset of rheumatoid arthritis by 7 years

    Science.gov (United States)

    Liu, Yang; Wen, Hong-yan; Wang, Li-hua; Wang, Chen

    2017-01-01

    Abstract Introduction: The co-existence of focal segmental glomerulosclerosis (FSGS) and rheumatoid arthritis (RA), presenting either together or in succession, is very rare. A variety of histopathological features in the clinical renal disease may occur in RA. Only 8 studies have previously reported this poorly understood connection. Clinical findings/diagnoses: A case of a 54-year-old male with RA lasting for more than 7 years developed cheirarthritis as the first signs. Symmetric polyarthralgia and multiple swollen joints throughout the body were followed, accompanied with morning stiffness. Gradually, he suffered from albuminuria, hypoalbuminemia, edema, and hyperlipidemia in 2014. The patient had the history of administering loxoprofen, celecoxib, leflunomide, and methotrexate. He was diagnosed as RA, nephrotic syndrome. Renal biopsy confirmed FSGS. Conclusion: Our case and the review of the literature indicate that FSGS is one of the causes of nephrotic syndrome in RA. It strongly suggested that RA patients with the abnormal kidney functions should be routinely screened for FSGS to guide the therapy, achieve both RA and FSGS remission, determine a prognosis, and avoid end-stage renal lesion. PMID:28072731

  3. [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.

  4. Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

    Directory of Open Access Journals (Sweden)

    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.

  5. Renoprotective effects of benazepril: current perspective.

    Science.gov (United States)

    Stompór, Tomasz; Napora, Maria; Olszewski, Artur

    2011-06-01

    Cardiovascular (CV) disease, its associated risk factors and continued progression run in parallel with renal deterioration (cardio-renal syndrome). Most guidelines promote early treatment, including the use of ACE inhibitors to control CV risk in patients with chronic renal failure. The renoprotective effects of the ACE inhibitor, benazepril, independent of blood pressure control, have been demonstrated, as monotherapy or in combination with amlodipine or hydrochlorothiazide, in large clinical trials: Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) and Gauging Albuminuria Reduction with Lotrel in Diabetic Patients with Hypertension (GUARD) in patients with mild-to-severe chronic kidney disease. In the ACCOMPLISH trial, CV outcomes and renoprotective effects were greater in patients receiving benazepril in combination with amlodipine; the GUARD trial demonstrated that combined benazepril/hydrochlorothiazide was more effective than amlodipine combined with benazepril in reducing baseline urinary albumin:creatinine ratio and normalizing urinary albumin:creatinine ratio in patients with baseline microalbuminuria, although this effect was accompanied with a greater decrease in glomerular filtration rate than with benazepril/amlodipine. While this is not a study in patients with overt renal disease (patients had severe CV diseases), the ACCOMPLISH trial is the first large study to date to show the added benefit of combining ACE inhibitors and calcium-channel blockers in renal protection. Future large, well-controlled trials, designed to evaluate hard renal outcomes, are required to identify which patients will benefit most from particular combination treatment strategies in renoprotection.

  6. 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.

  7. Reactive immunization suppresses advanced glycation and mitigates diabetic nephropathy.

    Science.gov (United States)

    Shcheglova, Tatiana; Makker, Sudesh; Tramontano, Alfonso

    2009-05-01

    Agents that inhibit glycation end products by reducing the carbonyl load from glycation and glycoxidation are an emerging pharmacologic approach to treat complications of diabetes. We previously demonstrated that antibodies generated to the glycoprotein keyhole limpet hemocyanin (KLH) can cross-link with reactive carbonyl residues on protein conjugates. Here, we immunized streptozotocin-induced diabetic rats with KLH to assess the capacity of the elicited antibodies to intercept carbonyl residues on glycated proteins and to mitigate glycation-related pathology. Compared with diabetic rats immunized with adjuvant alone, KLH-immunized diabetic rats had decreased levels of glycated peptides in sera and demonstrated a reduction in albuminuria, proteinuria, deposition of glycation end products in the kidney, and histologic damage. In vitro, low molecular weight glycated peptides from rat serum reacted with anti-KLH antibodies at a faster rate than normal IgG and selectively modified the lambda chains. The reaction products contained peptide sequences from type I collagen alpha chain, albumin, and LDL receptor-related protein. These adduction reactions were inhibited by free KLH and by reduction of glycated peptides with borohydride. In summary, these results suggest that inherent reactivity of Ig light chains provides a natural mechanism for the removal of cytotoxic glycation products. This reactivity can be augmented by glycoprotein-specific reactive immunization, a potential biopharmaceutical approach to glycation-related pathology.

  8. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    Science.gov (United States)

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  9. Renin-angiotensin-aldosterone system blockade in chronic kidney disease: current strategies and a look ahead.

    Science.gov (United States)

    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.

  10. Indoxyl sulphate and kidney disease: Causes, consequences and interventions.

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    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.

  11. 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.

  12. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

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    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.

  13. Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

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    Jing Zhang

    2016-09-01

    Full Text Available Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN. Endoplasmic reticulum (ER stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p. twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.

  14. 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.

  15. 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.

  16. AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.

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    Itay Israel Shemesh

    Full Text Available Diabetic nephropathy (DN is characterized by proliferation of mesangial cells, mesangial expansion, hypertrophy and extracellular matrix accumulation. Previous data have cross-linked PKB (AKT to TGFβ induced matrix modulation. The non-toxic compound AS101 has been previously shown to favorably affect renal pathology in various animal models and inhibits AKT activity in leukemic cells. Here, we studied the pharmacological properties of AS101 against the progression of rat DN and high glucose-induced mesangial dysfunction. In-vivo administration of AS101 to Streptozotocin injected rats didn't decreased blood glucose levels but ameliorated kidney hypotrophy, proteinuria and albuminuria and downregulated cortical kidney phosphorylation of AKT, GSK3β and SMAD3. AS101 treatment of primary rat glomerular mesangial cells treated with high glucose significantly reduced their elevated proliferative ability, as assessed by XTT assay and cell cycle analysis. This reduction was associated with decreased levels of p-AKT, increased levels of PTEN and decreased p-GSK3β and p-FoxO3a expression. Pharmacological inhibition of PI3K, mTORC1 and SMAD3 decreased HG-induced collagen accumulation, while inhibition of GSK3β did not affect its elevated levels. AS101 also prevented HG-induced cell growth correlated to mTOR and (rpS6 de-phosphorylation. Thus, pharmacological inhibition of the AKT downstream pathway by AS101 has clinical potential in alleviating the progression of diabetic nephropathy.

  17. Comprehensive approach to diabetic nephropathy

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    Bancha Satirapoj

    2014-09-01

    Full Text Available Diabetic nephropathy (DN is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin–angiotensin–aldosterone system inhibitors (RAASi. The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.

  18. Therapeutic insight into molsidomine, a nitric oxide donor in streptozotocin-induced diabetic nephropathy in rats

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    Nathani Minaz

    2016-01-01

    Full Text Available Background: Diabetes-induced oxidative stress and hypertension play a major role in the development of nephropathy. Hence, the present study was undertaken to evaluate the protective effects of molsidomine, a nitric oxide donor in streptozotocin (STZ-induced