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Sample records for albuminuria

  1. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  2. Albuminuria

    Science.gov (United States)

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  3. Albuminuria reflects widespread vascular damage. The Steno hypothesis

    DEFF Research Database (Denmark)

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

    1989-01-01

    Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative reti...

  4. Cystatin C, Albuminuria, and Mortality Among Older Adults With Diabetes

    OpenAIRE

    de Boer, Ian H.; Katz, Ronit; Cao, Jie J; Fried, Linda F.; Kestenbaum, Bryan; Mukamal, Ken; Rifkin, Dena E.; Sarnak, Mark J.; Shlipak, Michael G.; Siscovick, David S.

    2009-01-01

    OBJECTIVE Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population. RESEARCH DESIGN AND METHODS This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (...

  5. Albuminuria: Prevalence, associated risk factors and relationship with cardiovascular disease

    OpenAIRE

    Chen, Fang; Yang, Wenying; Weng, Jianping; Jia, Weiping; Ji, Linong; Xiao, Jianzhong; Shan, Zhongyan; Liu, Jie; Tian, Haoming; Ji, Qiuhe; Zhu, Dalong; Ge, Jiapu; Lin, Lixiang; Chen, Li; Guo, Xiaohui

    2013-01-01

    Abstract Aims/Introduction To investigate the prevalence and associated risk factors of microalbuminuria, and to explore the relationship between albuminuria and cardiovascular disease (CVD). Materials and Methods A nationally representative sample of 38,203 Chinese participants was categorized by different levels of urinary albumin‐to‐creatinine ratio (ACR; 0 –10 mg/g, 10 –20 mg/g, 20 –30 mg/g, 30 –300 mg/g). The prevalence of albuminuria was compared by using a single urinary ACR cut‐off po...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  7. Albuminuria and associated risk factors in type II diabetics

    International Nuclear Information System (INIS)

    Objective: To determine the frequency of microalbuminuria (MA) and its associated medical risk factors in type II diabetic patients. Materials and Methods: Study population included 150 type II diabetic patients (70 women, 80 men) attending outpatient department of the hospital. Patients having clinical albuminuria and with other causes of proteinuria were excluded. Results: Women and men were of comparable ages. Women (26.4 kg/m/sup 2/) had higher body mass index (BMI) than men 24.3 kg/m/sup 2/). The frequency of MA was 46.7%, higher in males (50.6%) than females (41.5%). Fasting plasma glucose HbA/sub 1c/ levels were significantly higher in patients with MA compared to those with normo albuminuria (p < 0.001). The microalbuminuria patients had significantly decreased HDL-c levels compared to normoalbuminuric subjects (p< 0.001). However, no relation of MA with age, gender, known duration of diabetes, BMI, history of smoking, hypertension and serum: total cholesterol, LDL-c, triglyceride, urea and creatinine was found. Conclusion: There is a strong association of poor glycaemic control and decreased HDL-c levels with the presence of micro albuminuria. (author)

  8. 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...... an individual, we tested whether the variability and discordance in systolic blood pressure (SBP) and albuminuria response to ARB therapy are associated with its long-term effect on cardiovascular outcomes....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    The objective of this cross-sectional study was to investigate risk markers indicating the presence of albuminuria in patients with hypertension in rural sub-Saharan Africa (SSA). Urine albumin-creatinine ratio, glycated hemoglobin (HbA1c ), blood pressure, anthropometry, and other patient...... significantly associated with albuminuria. Only dysregulated DM and age were the conventional risk markers that seemed to suggest albuminuria among patients with hypertension in rural SSA....

  10. Diabetes mellitus, hypertension and albuminuria in rural Zambia

    DEFF Research Database (Denmark)

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

    2013-01-01

    OBJECTIVE: To assess albuminuria in rural Zambia among patients with diabetes mellitus only (DM group), hypertension only (HTN group) and patients with combined DM and HTN (DM/HTN group). METHODS: A cross-sectional survey was conducted at St. Francis Hospital in the Eastern province of Zambia...... of DM or HTN. RESULTS: A total of 193 participants were included (DM group: n = 33; HTN group: n = 92; DM/HTN group: n = 68). The participants in the DM group used insulin more frequently as diabetes medication than the DM/HTN group (P < 0.05). Furthermore, the DM group was younger and had lower BMI...

  11. 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.

  12. 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.

  13. ROLE OF URINARY ALBUMIN TO CREATININE RATIO AND SPOT ALBUMINURIA IN PREDICTING SIGNIFICANT ALBUMINURIA IN PATIENTS OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Gitanjali

    2014-01-01

    Full Text Available INTRODUCTION: Diabetic nephropathy is the most common cause of End Stage Renal Disease (ESRD. The earliest clinical evidence of nephropathy is microalbuminuria. The commonly used investigations to diagnose microalbuminuria include 24 hours urinary Albumin Excretion Rate (AER , Albumin to Creatinine ratio (ACR and spot microalbuminuria. These latter two methods have been found to be convenient , cost effective and efficient in screening patients of microalbuminuria when compared with 24 hour collections . AIM OF STUDY : T he present study was conducted to know whether ACR or spot microalbuminuria alone can predict and quantify microalbuminuria in patients with Diabetic Nephropathy. METHODOLOGY :100 known patients of type II DM were enrolled for the study. 24 hour u rinary sample was taken to quantify albuminuria and spot urine sample was taken for ACR and microalbuminuria. The results obtained by ACR and spot microalbuminuria were compared with the gold standard 24 hours urinary protein measurement. RESULTS :Sensitivit y and specificity for predicting true microalbuminuria were found to be 91% and 75% respectively for ACR. Its positive predictive value was 57% and negative predictive value was 90%. Sensitivity and specificity were found to be 92% and 82% for spot microal buminuria with positive predictive value of 40% and negative predictive value of 95%. CONCLUSION: The low specificity and low positive predictive value of ACR and spot microalbumin does not support their use for quantifying urinary albumin excretion and it w as concluded that these methods alone cannot be relied upon for quantification of albuminuria. However the high sensitivity and negative predictive value of the tests suggests that these are good routine outdoor screening tests for finding out those patien ts who should undergo quantification by 24 hours urine albumin excretion. KEYWORDS: Albumin to Creatinine Ratio , Spot microalbuminuria , 24 - hr urinary protein , Diabetes

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

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    Cheng-Hung Lee

    2015-01-01

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

  15. Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes

    OpenAIRE

    Afaf Al-Adsani

    2012-01-01

    There are no available data about the factors associated with diabetic nephropathy (DN) in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (6...

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

    OpenAIRE

    Köbberling, Johannes; Schroeder, Andreas; Heiderhoff, Marc

    2005-01-01

    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 cou...

  17. Association of Relatives of Hemodialysis Patients with Metabolic Syndrome, Albuminuria and Framingham Risk Score

    OpenAIRE

    Huang, Jiun-Chi; Chen, Szu-Chia; Lin, Ming-Yen; Chang, Jer-Ming; Hwang, Shang-Jyh; Tsai, Jer-Chia; Chen, Hung-Chun

    2014-01-01

    Background and Aim Metabolic syndrome (MetS), albuminuria, and the Framingham Risk Score (FRS) are significant predictors for cardiovascular disease (CVD). However, the relationship and clinical significance of these CVD predictors in individuals with a family history of end-stage renal disease (ESRD) are unclear. We investigated the association of relatives of hemodialysis (HD) patients with MetS, albuminuria, and the FRS. Methods One hundred and sixty-six relatives of HD patients and 374 ag...

  18. Angiopoietin-2 Is Associated with Albuminuria and Microinflammation in Chronic Kidney Disease

    OpenAIRE

    Chang, Fan-Chi; Lai, Tai-Shuan; Chiang, Chih-Kang; Chen, Yung-Ming; Wu, Ming-Shiou; Chu, Tzong-Shinn; Wu, Kwan-Dun; Lin, Shuei-Liong

    2013-01-01

    Although cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD), the pathophysiology is not thoroughly understood. Given that elevated albuminuria or circulating angiopoietin-2 associates with CVD and mortality in CKD patients, we were intrigued by the relationship between albuminuria and angiopoietin-2. A total of 416 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as normoalbuminuria (300 mg/g). The leve...

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

    OpenAIRE

    McMahon, Gearoid M; Hwang, Shih-Jen; Tanner, Rikki M.; 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 ...

  20. 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.

  1. Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Afaf Al-Adsani

    2012-01-01

    Full Text Available There are no available data about the factors associated with diabetic nephropathy (DN in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (66.2% women and 52 (33.8% men, with a mean age of 49.1 ± 10.1 years and a median duration of diabetes for 6 years. Hypertension was found in 60.8% of the patients and 16.3% had an HbA 1c <7%. Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. In the univariate analysis, the factors that were significantly associated with albuminuria were hypertension - both systolic and diastolic blood pressure levels, HbA 1c , retinopathy, duration of diabetes, and modality of treatment. Multiple logistic regression analysis indicated that hyper-tension was the main independent risk factor associated with albuminuria (OR 4.1, 95% CI 1.1- 15.0; P = 0.03. In conclusion, although albuminuria is common among Kuwaiti adults with type 2 diabetes, the prevalence is lower than that reported for other populations in spite of the poor glycemic control and the high prevalence of hypertension. Factors associated with albuminuria appear to be similar to other populations, and hypertension was the most independent factor. Early recognition and treatment of hypertension is an important strategy to prevent or delay DN as well as cardiovascular morbidity and mortality. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN.

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

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    Vivek

    2015-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes

    Science.gov (United States)

    Bjornstad, P.; Maahs, D. M.; Johnson, R. J.; Rewers, M.; Snell-Bergeon, J. K.

    2014-01-01

    Aim To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes. Method We enrolled 81 people aged 30–48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ≥20 µg/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate diabetes duration, sex, serum uric acid, HbA1c, systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensinconverting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model. Results Estimated insulin sensitivity was significantly higher at both baseline (4.6±1.2 vs 3.4±1.7; P=0.002) and follow-up (5.2±1.9 vs. 3.5±1.7; Pdiabetes is a potential therapeutic target to increase rates of regression of albuminuria. PMID:25303233

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

    Science.gov (United States)

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

    2013-06-01

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

  6. YKL-40 levels are independently associated with albuminuria in type 2 diabetes

    DEFF Research Database (Denmark)

    Røndbjerg, Anne K; Omerovic, Emina; Vestergaard, Henrik

    2011-01-01

    YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular morta...... mortality in the general population. In the present study YKL-40 levels were examined in patients with type 2 diabetes (T2D) with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.......YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular...

  7. Albuminuria Is Associated with Elevated Acute Phase Reactants and Proinflammatory Markers in HIV-Infected Patients Receiving Suppressive Combination Antiretroviral Therapy

    OpenAIRE

    O-charoen, Pichaya; Ndhlovu, Lishomwa C.; Gangcuangco, Louie Mar A; Keating, Sheila M.; Norris, Philip J.; Ng, Roland C.K.; Mitchell, Brooks I.; Shikuma, Cecilia M.; Chow, Dominic C.

    2014-01-01

    Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Taleb Nadine

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. 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

  17. Angiopoietin-2 is associated with albuminuria and microinflammation in chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Fan-Chi Chang

    Full Text Available Although cardiovascular disease (CVD is the leading cause of mortality in patients with chronic kidney disease (CKD, the pathophysiology is not thoroughly understood. Given that elevated albuminuria or circulating angiopoietin-2 associates with CVD and mortality in CKD patients, we were intrigued by the relationship between albuminuria and angiopoietin-2. A total of 416 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as normoalbuminuria (300 mg/g. The levels of plasma angiopoietin-2 and vascular endothelial growth factor (VEGF increased, and soluble Tie-2 decreased in the subgroups of albuminuria; whereas angiopoietin-1 did not change. Linear regression showed a positive correlation between urine albumin-creatinine ratio (ACR and plasma angiopoietin-2 (correlation coefficient r = 0.301, 95% confidence interval 0.211-0.386, P<0.0001, but not between ACR and VEGF or soluble Tie-2. Multivariate linear regression analysis showed that plasma angiopoietin-2 was independently associated with ACR (P = 0.025. Furthermore, plasma angiopoietin-2 was positively correlated with high sensitive C-reactive protein (r = 0.114, 95% confidence interval 0.018-0.208, P = 0.020. In conclusion, plasma angiopoietin-2 was associated with albuminuria and markers of systemic microinflammation in CKD patients. Although previous evidence has shown that angiopoietin-2 destabilizes vasculature and induces inflammation in different scenarios, further study will be required to delineate the role of angiopoietin-2 in albuminuria and microinflammation in CKD patients.

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

    Directory of Open Access Journals (Sweden)

    Köbberling, Johannes

    2005-11-01

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

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

    Directory of Open Access Journals (Sweden)

    John M Flack

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jiun-Chi Huang

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

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

    OpenAIRE

    Samoyavcheva S.V.; Shkarin Vl.V.

    2013-01-01

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

  2. 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...

  3. Urinary proteomics in chronic kidney disease: diagnosis and risk of progression beyond albuminuria

    OpenAIRE

    Øvrehus, Marius Altern; Zürbig, Petra; Vikse, Bjørn Egil; Hallan, Stein

    2015-01-01

    Background: The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed. Results: We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized p...

  4. Relation of Kidney Function and Albuminuria with Atrial Fibrillation (From the Heart and Soul Study)

    OpenAIRE

    McManus, David D.; Corteville, David C. M.; Shlipak, Michael G.; Whooley, Mary A.; Ix, Joachim H

    2009-01-01

    Atrial fibrillation (AF) is common in end-stage renal disease (ESRD), but the relationship between more modest decrements in kidney function or albuminuria with AF is uncertain. Among 956 outpatients with coronary heart disease (CHD), we assessed kidney function by 3 methods (cystatin C-based [eGFRcys] and creatinine-based [eGFRCr] estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio [ACR]) and prevalent AF by surface electrocardiogram. Multivariable logistic regressi...

  5. 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 and......±12 years, UACR (geometric mean,IQR): 99(37-233) mg/g, (51)Cr-EDTA-GFR: 94±22 ml/min/1.73m(2), HbA1c: 9.0±1.1%, glucose variability (calculated as SD): 4.0±1.0 mmol/l; no groups differences (P≥0.06 for all). After 1 year, change in UACR was (mean(95%CI)) -13(-39-22) with SAP vs. 30(-12-92)% on MDI treatment...

  6. Albuminuria is associated with elevated acute phase reactants and proinflammatory markers in HIV-infected patients receiving suppressive combination antiretroviral therapy.

    Science.gov (United States)

    O-charoen, Pichaya; Ndhlovu, Lishomwa C; Gangcuangco, Louie Mar A; Keating, Sheila M; Norris, Philip J; Ng, Roland C K; Mitchell, Brooks I; Shikuma, Cecilia M; Chow, Dominic C

    2014-12-01

    Albuminuria among HIV-infected individuals has been found to be associated with cardiovascular disease (CVD) and mortality. Inflammation has been associated with albuminuria. The pathophysiology of albuminuria in HIV-infected individuals is poorly understood. We investigated the association of albuminuria with inflammatory biomarkers among HIV-infected individuals on combination antiretroviral therapy (cART). This is a cross-sectional analysis of participants enrolled in the Hawaii Aging with HIV-Cardiovascular Cohort. Plasma inflammatory biomarkers were assessed using the Milliplex Human Cardiovascular disease multiplex assays. A random urine sample was collected for albumin measurement. Albuminuria was defined as urine albumin-to-creatinine ratio of ≥30 mg/g. Framingham risk score was calculated and divided into three classes. Simple and multivariable logistic regression analyses were utilized to assess the correlation between plasma inflammatory biomarkers and albuminuria and were adjusted for Framingham risk category. Among 111 HIV-infected patients [median (IQR) age of 52 (46-57) years, 86% male, median (IQR) CD4 count of 489 (341-638) cells/mm(3), 85% with HIV RNA CVD risk factors. This study showed an association between inflammation and albuminuria independent of previously reported risk factors for albuminuria in HIV-infected subjects who were on combination antiretroviral therapy (cART). Chronic inflammation despite potent antiretroviral treatment may contribute to higher rates of albuminuria among HIV-infected patients. PMID:25205472

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nidhi Jain

    2016-06-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Samoyavcheva S.V.

    2013-12-01

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

  11. Diverging Association of Reduced Glomerular Filtration Rate and Albuminuria With Coronary and Noncoronary Events in Patients With Type 2 Diabetes

    Science.gov (United States)

    Solini, Anna; Penno, Giuseppe; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Arosio, Maura; Trevisan, Roberto; Vedovato, Monica; Cignarelli, Mauro; Andreozzi, Francesco; Nicolucci, Antonio; Pugliese, Giuseppe

    2012-01-01

    OBJECTIVE Although a reduced estimated glomerular filtration rate (eGFR) was shown to be a powerful independent predictor of cardiovascular disease (CVD), other studies suggested that it confers a much lower risk than albuminuria alone, whereas the combination of the two abnormalities is associated with multiplicative risk. This study aimed at assessing the independent association of previous CVD events, either total or by vascular bed, with eGFR and albuminuria and chronic kidney disease (CKD) phenotypes. RESEARCH DESIGN AND METHODS This cross-sectional study evaluated 15,773 patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study in 19 outpatient diabetes clinics in years 2007–2008. Albuminuria was assessed by immunonephelometry or immunoturbidimetry. GFR was estimated by the simplified Modification of Diet in Renal Disease Study and the Chronic Kidney Disease-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL/min/1.73 m2 or micro- or macroalbuminuria. Major acute CVD events were adjudicated based on hospital discharge records or specialist visits. RESULTS CVD risk increased linearly with eGFR decline and albuminuria and became significant for values <78 mL/min/1.73 m2 and ≥10.5 mg/24 h, respectively. Beyond traditional CVD risk factors, total CVD showed an independent association with albuminuria alone (odds ratio 1.20 [95% CI 1.08–1.33]), reduced eGFR alone (1.52 [1.34–1.73]), and both abnormalities (1.90 [1.66–2.19]). However, coronary events were associated predominantly with reduced eGFR alone, whereas cerebrovascular and peripheral events showed a stronger correlation with the albuminuric CKD phenotypes. CONCLUSIONS These data, although cross-sectional, show that reduced eGFR, irrespective of albuminuria, is associated with significant CVD, particularly in the coronary district. PMID:22124714

  12. Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria

    DEFF Research Database (Denmark)

    Deckert, T; Kofoed-Enevoldsen, A; Vidal, P; Nørgaard, K; Andreasen, H B; Feldt-Rasmussen, B

    1993-01-01

    techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26......-64 A) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p < 0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular...

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

    DEFF Research Database (Denmark)

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

    1981-01-01

    .001), the urinary albumin excretion rate diminished from 1447 to 613 micrograms/min (P less than 0.005), and GFR declined from 96 to 89 ml/in/1.73 m2 (P less than 0.01). A linear relationship between mean blood pressure and the logarithm of the albuminuria was found (r = 0.48, P less than 0.01). Arterial...... 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...

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

    Science.gov (United States)

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

    2014-04-01

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

  15. Striking association between urinary cadmium level and albuminuria among Torres Strait Islander people with diabetes

    International Nuclear Information System (INIS)

    Objectives: Indigenous people of the Torres Strait (Australia) have greater potential for cadmium exposure and renal damage than other Australians due to high cadmium in some traditional seafood and a high prevalence of Type 2 diabetes, hypertension, smoking, and obesity. This study explored associations between albuminuria and an index of cadmium exposure (urinary cadmium excretion) in the presence and absence of Type 2 diabetes. Research design and methods: Two population-based, cross-sectional studies were undertaken in the Torres Strait to obtain data on body mass index (BMI), blood pressure, chronic disease, smoking, urinary cadmium, and albumin creatinine ratio (ACR). Results: Age- and BMI-adjusted urinary cadmium levels were significantly higher (p<0.01) among people with diabetes and albuminuria (n=22, geometric mean (GM) 1.91 μg Cd/g creatinine) compared to those with diabetes and normal ACR (n=21, GM 0.74 μg Cd/g creatinine). Urinary cadmium was also strongly associated (p<0.001) with ACR among people with diabetes in regression models and remained significant after controlling for age, sex, BMI, smoking status, and hypertension (or continuous systolic and diastolic measurements). Conclusions: While the study has methodological limitations and the nature of the association is unclear, the striking dose-dependent links between markers of cadmium exposure and of Type 2 diabetic nephropathy highlight the need for further definitive research on the health effects of cadmium in the presence of diabetes

  16. Comparison of urine collection methods for albuminuria assessment in young children.

    Science.gov (United States)

    van den Belt, S M; Gracchi, V; de Zeeuw, D; Heerspink, H J L

    2016-07-01

    Cotton wool or pantyliners placed in a diaper can be used as urine collection devices for albuminuria measurements in young, not continent children. We tested a new collection method (PeeSpot(R)) for its analytical performance, and compared it with the pantyliner technique. Eighty-one urine samples with a wide range of albuminuria were pipetted on the pantyliner and PeeSpot in duplicate. These were incubated for 3h at 37°C (simulating the time a toddler wears a diaper), and subsequently 72h at room temperature (simulating transport to a central laboratory). Urine was extracted by centrifugation and albumin concentration (UAc) was measured. UAC measured by the two methods was compared with UAC in an unprocessed reference aliquot stored for 75h at 4°C. Bias (mean percentage UAC difference between test and reference), precision (interquartile range of the UAC difference) and accuracy (proportion of samples within 30% of reference UAC) were calculated. Median UAC in the reference aliquot was 66.0mg/L [IQR 25.0-211.0], pantyliner 32.0mg/L [4.7-165.0; Pplot showed an underestimation for the pantyliner but not for the PeeSpot. The PeeSpot is an accurate and precise tool for collecting urine for albumin measurement in young children and should be preferred over the alternative cotton wool collection technique. PMID:27129631

  17. 2 year followup of patients with diabetes mellitus nephropathy showing albuminuria reversal following angiotensin converting enzyme inhibitors

    Directory of Open Access Journals (Sweden)

    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.

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

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    G Emerens Wensink

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. The predictive value of albuminuria for renal and nonrenal natural deaths over 14 years follow-up in a remote aboriginal community

    OpenAIRE

    Wang, Zaimin; Wendy E. Hoy

    2012-01-01

    Background Australian aboriginal people living in remote regions have extraordinary higher rates of mortality compared with other Australian ethnicities. Albuminuria marks the underlying renal disease. This study assessed the predictive value of albuminuria for nonrenal and renal deaths in a remote Australian aboriginal community over a follow-up period of >14 years. Methods From 1992 to 1997, 85% of community members participated in a health screen, which included measurement of urine albumi...

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

    OpenAIRE

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Meysamie Alipasha

    2008-08-01

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

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

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    Sang Youb Han

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

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

    LENUS (Irish Health Repository)

    Collier, Geraldine

    2012-02-01

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

  9. 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.

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

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    Hung-Yu Chang

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

  11. 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.

  12. 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.

  13. 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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    , with moderate SCORE or with high-intermediate or high FRS (all P hazard ratio 2.7 (1.6-4.8)] and 61...... years [hazard ratio 2.7 (1.5-4.7)], moderate [hazard ratio 2.4 (1.6-3.7)] or high SCORE risk group [hazard ratio 2.3 (1.2-4.7)] and low-intermediate [hazard ratio 3.3 (1.5-7.0)], high-intermediate [hazard ratio 2.3 (1.5-3.5)] and high FRS risk group [hazard ratio 2.0 (1.4-3.0)]. CONCLUSION: SVD...... atherosclerotic plaques or albuminuria defined as urine albumin/creatinine ratio at least 90th percentile of 0.73/1.06 mg/mmol men/women. In 2006, the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and hospitalization for ischemic heart disease was recorded (n...

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

    Directory of Open Access Journals (Sweden)

    Chang Man-huei

    2010-11-01

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

  17. Urinary serine proteases and activation of ENaC in kidney-implications for physiological renal salt handling and hypertensive disorders with albuminuria

    DEFF Research Database (Denmark)

    Svenningsen, Per; Andersen, Henrik; Nielsen, Lise H; Jensen, Boye L.

    2015-01-01

    in acute conditions with proteinuria, like nephrotic syndrome and preeclampsia, and in chronic diseases, such as diabetes with microalbuminuria. A vast literature on renin-angiotensin-aldosterone system and volume homeostasis from the last four decades show a number of common characteristics for...... conditions with albuminuria compatible with impaired renal Na(+) excretion: hypertension and volume retention is secondary to proteinuria in, e.g., preeclampsia and nephrotic syndrome; plasma concentrations of renin, angiotensin II, and aldosterone are frequently suppressed in proteinuric conditions, e...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jong Chul Won

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

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

    Institute of Scientific and Technical Information of China (English)

    吕恩君

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    2013-01-01

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

  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; Rossing, P

    2015-01-01

    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......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...

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

    DEFF Research Database (Denmark)

    Rossing, K; Christensen, P K; Hovind, Peter; Parving, H-H

    2005-01-01

    AIMS/HYPOTHESIS: We evaluated the impact of remission of nephrotic-range albuminuria (>2500 mg/24 h) (NRA) on end-stage renal disease (ESRD) and mortality in type 2 diabetic patients with nephropathy. METHODS: This was a follow-up observational study involving all 79 patients (35%; 62 men, 17 women......) with NRA from a cohort of type 2 diabetic patients with nephropathy that was followed for at least 3 years at the Steno Diabetes Center (n=227). Patients were followed from the onset of NRA until death or January 2005. The mean age (+/-SD) was 60+/-8 years and known diabetes duration was 14+/-7 years....... Remission of NRA was defined as sustained albuminuria <600 mg/24 h for at least 1 year. RESULTS: The duration of follow-up after onset of NRA was 6.5 years (range 2-20 years). Remission was induced in 20 (25%) of the patients, all treated with ACE inhibitors or angiotensin-II receptor blockers. Remission...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hiroyuki Ito

    2015-01-01

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

  8. Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study

    Directory of Open Access Journals (Sweden)

    James Lynwen A

    2006-09-01

    Full Text Available Abstract Background Previous studies have shown that in male rats, exposure to maternal protein restriction either in utero or whilst suckling can have profound effects on both longevity and kidney telomere lengths. This study monitored albuminuria longitudinally in male rats whose mothers had been protein restricted either during pregnancy or lactation. Methods Pregnant Wistar rats were fed either a 20% ('control' or an 8% protein ('low protein' diet. At two days of age some of the pups were cross-fostered to dams fed the diet that was not given to their biological mothers. At weaning all pups were fed standard chow. Urine samples were collected for the measurement of albumin and creatinine at monthly intervals from two months-of-age. Longitudinal analysis was then performed using repeated measures analysis of variance. Results Overall estimated marginal geometric mean (95 % confidence interval urine albumin to creatinine ratios were: control animals 79.5 (57.2~110.6 g/mol (n = 6 litters, 24 animals in total, those exposed in utero to maternal protein restriction 71.0 (47.4~106.5 (n = 4 litters, 16 animals in total, those exposed to maternal protein restriction whilst suckling 21.2 (14.7~30.4 (n = 5 litters, 20 animals in total (p Conclusion Animals exposed to maternal protein restriction whilst suckling exhibited lower urine albumin excretions during much of adult life. As urine albumin can be nephrotoxic, these rats therefore appeared to be relatively protected against future nephron damage like that previously observed in animals exposed to maternal protein restriction in utero.

  9. 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。

  10. 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.

  11. Morphine Induces Albuminuria by Compromising Podocyte Integrity

    OpenAIRE

    Lan, Xiqian; Rai, Partab; Chandel, Nirupama; Cheng, Kang; Lederman, Rivka; Saleem, Moin A; Mathieson, Peter W.; Husain, Mohammad; Crosson, John T.; Gupta, Kalpna; Malhotra, Ashwani; Singhal, Pravin C.

    2013-01-01

    Morphine has been reported to accelerate the progression of chronic kidney disease. However, whether morphine affects slit diaphragm (SD), the major constituent of glomerular filtration barrier, is still unclear. In the present study, we examined the effect of morphine on glomerular filtration barrier in general and podocyte integrity in particular. Mice were administered either normal saline or morphine for 72 h, then urine samples were collected and kidneys were subsequently isolated for im...

  12. 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

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

    Science.gov (United States)

    Grauer, Gregory F

    2007-03-01

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

  14. Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria

    OpenAIRE

    Xu, Yizhen; Zhang, Zhaoyun; Hu, Ji; Stillman, Isaac E.; Leopold, Jane A.; Handy, Diane E.; Loscalzo, Joseph; Stanton, Robert C.

    2010-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway and the principal source of NADPH, a major cellular reductant, and is central to cell survival. Our previous work showed that diabetes and increased aldosterone are acquired forms of G6PD deficiency, leading to decreased G6PD activity and NADPH levels and damage to kidney tissue and endothelial cells. In this study, G6PD-deficient mice were studied to test the hypothesis that decreased G6PD a...

  15. 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.

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

    OpenAIRE

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Christensen, Cramer

    1984-01-01

    The aim of the study was to evaluate the influence of light to moderate dynamic work (450 kpm/min followed by 600 kpm/min during 20 min each) on the blood pressure and renal protein handling in insulin-dependent diabetic patients with incipient nephropathy (D3) (elevated baseline albumin excretion...... baseline diastolic blood pressure was elevated [92.1 mm Hg +/- 6.0 (mean +/- SD)] compared to D2 (80.9 mm Hg +/- 4.8, 2P = 0.003%) and C (79.5 mm Hg +/- 12.4, 2P = 1.2%). Baseline systolic blood pressure was not significantly different in the three groups, but systolic blood pressure was more elevated at...... 600 kpm/min in D3 (193.0 mm Hg +/- 23.0) compared to D2 (170.5 +/- 17.3, 2P = 1.2%) and C (157.5 mm Hg +/- 20.9, 2P = 0.07%). Baseline albumin excretion in D3 was 82.6 micrograms/min X/ divided by 2.5 (geometric mean X/ divided by tolerance factor) and during exercise the maximal albumin excretion...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    DEFF Research Database (Denmark)

    Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz; Andersen, Niels Holmark; Bek, Toke; Ingerslev, Jørgen; Mogensen, Carl Erik; Poulsen, Per Løgstrup

    2007-01-01

    in a stepwise manner from the control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and 59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group A; e.g. ICAM-1 [median...... (interquartile range)] 191 (160-217), 213 (189-262) and 316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r = 0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1, respectively). CONCLUSION...... three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased...

  3. Levels of albuminuria and risk of developing macroalbuminuria in type 2 diabetes: historical cohort study.

    Science.gov (United States)

    Chida, Shoma; Fujita, Yoshikuni; Ogawa, Akifumi; Hayashi, Akinori; Ichikawa, Raishi; Kamata, Yuji; Takeuchi, Akihiro; Takano, Koji; Shichiri, Masayoshi

    2016-01-01

    Although increased urinary albumin excretion may increase the risk of adverse renal outcomes in patients with diabetes, it remains unclear whether microalbuminuria is associated with a higher incidence of macroalbuminuria in the absence of non-diabetic kidney events that frequently develop during the long-term course of type 2 diabetes. This historical cohort study included patients with type 2 diabetes, spot urine albumin:creatinine ratio (ACR) <300 mg/gCr and normal serum creatinine concentrations treated between August 1988 and April 2015. Patients with any evidence suggesting non-diabetic kidney diseases at baseline were excluded. Over a median follow-up of 50 months, 70 of the 1760 included patients developed macroalbuminuria. Twenty-one of these patients were diagnosed with non-diabetic renal events. The five-year cumulative incidence of macroalbuminuria in patients with ACRs of 0-7.5 mg/gCr, 7.5-30 mg/gCr, 30-150 mg/gCr, and 150-300 mg/gCr were 0%, 0.53%, 3.5%, and 36.0%, respectively, with significant differences between each pair of ACR categories. In type 2 diabetes, higher urinary ACR, even within a level of normoalbuminuria, was associated with a greater incidence of macroalbuminuria when non-diabetic renal events were excluded. These results conflict with findings suggesting that microalbuminuria is a poor indicator for the progression of diabetic nephropathy. PMID:27210499

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. 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....

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin...... placebo for eight weeks. Then, after 4 weeks (the wash-out period), each patient received the drug he or she had not taken before for another 8 weeks. Systolic blood pressure was lowered by 8 mmHg from 127 (114-139) mmHg (P less than 0.01) and diastolic by 5 mmHg from 81 (70-87) mmHg (P less than 0...... 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...

  9. Plasma Lipoprotein(a) Levels Are Associated with Mild Renal Impairment in Type 2 Diabetics Independent of Albuminuria

    OpenAIRE

    Lin, Jennie; Reilly, Muredach P.; Terembula, Karen; Wilson, F. Perry

    2014-01-01

    Background CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function. Methods In the Penn Diabetes Heart ...

  10. Glomerular filtration rate and albuminuria predict mortality independently from coronary artery calcified plaque in the Diabetes Heart Study

    OpenAIRE

    Cox, Amanda J.; Hsu, Fang-Chi; Carr, J. Jeffrey; Freedman, Barry I.; Bowden, Donald W.

    2013-01-01

    Background Risk stratification in individuals with type 2 diabetes (T2D) remains an important priority in the management of associated morbidity and mortality, including from cardiovascular disease (CVD). The current investigation examined whether estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) were independent predictors of CVD-mortality in European Americans (EAs) with T2D after accounting for subclinical CVD. Methods The family-based Diabetes Heart Stu...

  11. Neither Proteinuria Nor Albuminuria Is Associated With Endothelial Dysfunction in HIV-Infected Patients Without Diabetes or Hypertension

    OpenAIRE

    Gupta, Samir K.; Shen, Changyu; Mather, Kieren J.; Agarwal, Rajiv; Dubé, Michael P.

    2011-01-01

    It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and ...

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

    OpenAIRE

    Weir, Matthew R

    2008-01-01

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

  13. 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; Olsen, Niels Vidiendal

    1996-01-01

    -85) (median with quartiles in parentheses) at high altitude. High altitude hypoxia increased Ualb from 3.2 micrograms min-1 (2.7-3.5) to 5.0 micrograms min-1 (3.3-6.6) (p <0.05); increased mean arterial blood pressure from 80 mmHg (73-95) to 102 mmHg (96 108) (p <0.01); decreased the effective renal plasma...... flow (ERPF) from 465 ml min-1 (412-503) to 410 ml min-1 (385-451) (p <0.05), and increased the filtration fraction from 24% (22-27) to 28% (26-29) (p <0.01). Glomerular filtration rate (GFR), and the renal clearances of lithium (CLi) and sodium (CNa) remained unchanged at high altitude. 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 <0.05) at high altitude, but had no effect on Ualb at sea level. In conclusion, high altitude hypoxia per se increases the urinary...

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

    OpenAIRE

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

    2016-01-01

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

  15. 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; Meng, Xiangyi; Parving, Hans-Henrik; Viberti, Giancarlo; Remuzzi, Giuseppe

    2010-01-01

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

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

    LENUS (Irish Health Repository)

    Cullen, Mr

    2013-10-11

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

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

    DEFF Research Database (Denmark)

    Weir, Matthew R; Hollenberg, Norman K; Zappe, Dion H; Meng, Xiangyi; Parving, Hans-Henrik; Viberti, Giancarlo; Remuzzi, Giuseppe

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Wachtell, K.; Olsen, M.H.

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  20. 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

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

    Institute of Scientific and Technical Information of China (English)

    韩志明; 姚筱; 刘炎

    2015-01-01

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

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  5. Bestimmung der Albuminausscheidung im Urin bei Diabetikern zur Vorsorge und Kontrolle der diabetischen Nephropathie

    OpenAIRE

    Schroeder, A.; Heiderhoff, M; KÖBBERLING, J.

    2005-01-01

    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...

  6. Linking adiponectin to proteinuria

    OpenAIRE

    Ahima, Rexford S.

    2008-01-01

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

  7. The correlates of urinary albumin to creatinine ratio (ACR) in a high risk Australian aboriginal community

    Science.gov (United States)

    2013-01-01

    Background Albuminuria marks renal disease and cardiovascular risk. It was estimated to contribute 75% of the risk of all-cause natural death in one Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an index of albuminuria. This study aims to examine the associations between demographic factors, anthropometric index, blood pressure, lipid-protein measurements and other biomarkers and albuminuria in a cross-sectional study in a high-risk Australian Aboriginal population. The models will be evaluated for albuminuria at or above the microalbuminuria threshold, and at or above the “overt albuminuria” threshold with the potential to distinguish associations they have in common and those that differ. Methods This was a cross-sectional study of 598 adults aged 18–76 years. All participants were grouped into quartiles by age. Logistic regression models were used to explore the correlates of ACR categories. Results The significant correlates were systolic blood pressure (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase (GGT) (marginally significant, p = 0.054) and serum albumin (negative association) for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP, uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin C and serum albumin (negative association) for overt albuminuria; and SBP, CRP and serum albumin only for microalbuminuria. Conclusions This is the most detailed modelling of pathologic albuminuria in this setting to date. The somewhat variable association with risk factors suggests that microalbuminuria and overt albuminuria might reflect different as well as shared phenomena. PMID:23947772

  8. The renoprotective effects of sulodexide

    Directory of Open Access Journals (Sweden)

    Olde Engberink RH

    2016-03-01

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

  9. 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.

  10. 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 < 30 mg 24 h-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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  12. Kidney Function and Progression of Coronary Artery Calcium in Community-Dwelling Older Adults (From the Rancho Bernardo Study)

    OpenAIRE

    Jassal, Simerjot Kaur; Chonchol, Michel; Laughlin, Gail A.; Cummins, Kevin M.; Smits, Gerard; Kramer, Caroline K.; Ix, Joachim H; Barrett-Connor, Elizabeth

    2012-01-01

    Longitudinal studies of the association of estimated glomerular filtration rate (eGFR) and albuminuria with coronary artery calcium, a measure of cardiovascular disease (CVD) burden, are few and contradictory. In this study, 421 community-dwelling men and women (mean age 67 years) without known heart disease had eGFR estimated by the Modification of Diet in Renal Disease equation and albuminuria assessed by urine albumin/creatinine ratio (ACR) between 1997–1999. Mean eGFR was 78 mL/min/1.73m2...

  13. 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 urin...

  14. 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

    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....

  15. EARLY SIGNS OF DIABETIC NEPHROPATHY AND ULTRASOUND CHARACTERISTICS OF KIDNEYS IN CHILDREN AND YOUTH WITH DIABETES MELLITUS TYPE 1

    Directory of Open Access Journals (Sweden)

    Hasanovic Evlijana

    2014-04-01

    Full Text Available Introduction:Diabetic nephropathy is a chronic complication in patients with diabetes mellitus typ 1, which leads to kidney disfunction. Aim: The aim of this study was to compare the metabolic control and albuminuria with ultrasound findings of morphometric measurements and registration Doppler signals of kidneys between children and youth with diabetes mellitus type 1 according to the duration of illness. Material and Methods: The retrospective-prospective study included 69 patients of both genders, that got diabetes mellitus type 1 when they were in the age from 2. to 25. years. Patients were divided into two groups according to the length of diabetes mellitus type 1: the first group was those whose illness had lasted for more than 10 years, and second group with duration of diabetes mellitus typ 1 less than 10 years. Results: No significant difference was registered between the groups regarding frequency of albuminuria, but the chance of it occurring are greater in patients with longer duration of diabetes mellitus type 1. Patients with albuminuria and diabetes mellitus type 1 duration over 10 years had higher glycated hemoglobin A1C, blood pressure, body mass index followed by enlarged volume of both kidneys. Patients with albuminuria and diabetes mellitus type 1 for less than 10 years had a higher creatinine clearance. Conclusion: Ultrasound dimensions and volume of the kidneys in patients with metabolic control parameters are useful for monitoring especially in the early stages of diabetic nephropathy.

  16. Impact of glycaemic control on the effect of direct renin inhibition in the AVOID study

    DEFF Research Database (Denmark)

    Persson, Frederik; Lewis, Julia B; Lewis, Edmund J; Rossing, Peter; Hollenberg, Norman K; Parving, Hans-Henrik

    2012-01-01

    Hyperglycaemia induces development and progression of microvascular complications in diabetes. A direct link between high glucose levels and intrarenal renin-angiotensin activation has been demonstrated. This post-hoc analysis assessed the influence of baseline glycaemic control on the reduction ...... albuminuria with aliskiren or placebo added to losartan in the Aliskiren in the EValuation of PrOteinuria In Diabetes (AVOID) study....

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

    International Nuclear Information System (INIS)

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

  18. 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

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

    OpenAIRE

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

    2009-01-01

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

  20. 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...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  3. 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

  4. General pripciples, instruments and adaptations

    International Nuclear Information System (INIS)

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

  5. 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 ...

  6. 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

  7. Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients.

    Science.gov (United States)

    Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Simões E Silva, Ana Cristina; Dusse, Luci Maria S; Reis, Janice Sepúlveda; Carvalho, Maria das Graças; Fernandes, Ana Paula; Gomes, Karina Braga

    2016-04-01

    Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease. PMID:27191046

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Secondary prevention of renal and cardiovascular disease: results of a renal and cardiovascular treatment program in an Australian aboriginal community.

    Science.gov (United States)

    Hoy, Wendy E; Wang, Zhiqiang; Baker, Philip R A; Kelly, Angela M

    2003-07-01

    Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency. PMID:12819325

  10. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  12. Impairment of renal function after islet transplant alone or islet-after-kidney transplantation using a sirolimus/tacrolimus-based immunosuppressive regimen.

    Science.gov (United States)

    Andres, Axel; Toso, Christian; Morel, Philippe; Demuylder-Mischler, Sandrine; Bosco, Domenico; Baertschiger, Reto; Pernin, Nadine; Bucher, Pascal; Majno, Pietro E; Bühler, Leo H; Berney, Thierry

    2005-11-01

    The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome. PMID:16221151

  13. 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

    0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. CONCLUSIONS: Based on the RADAR/JAPAN study, with short-term changes in risk markers......, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. DESIGN: We used the PRE score on data......, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30...

  14. Nuclear cardiology in Senegal: a luxury or a need?

    International Nuclear Information System (INIS)

    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)

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

    Weinrauch, Larry

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

  19. 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.

  20. Intravital imaging reveals angiotensin II–induced transcytosis of albumin by podocytes

    OpenAIRE

    Schießl, Ina Maria; Hammer, Anna; Kattler, Veronika; Gess, Bernhard; Theilig, Franziska; Witzgall, Ralph; Castrop, Hayo

    2016-01-01

    Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and ...

  1. Soluble α-Klotho as a Novel Biomarker in the Early Stage of Nephropathy in Patients with Type 2 Diabetes

    OpenAIRE

    Lee, Eun Young; Kim, Sang Soo; Lee, Ji-Sung; Kim, In Joo; Song, Sang Heon; Cha, Seung-Kuy; Park, Kyu-Sang; Kang, Jeong Suk; Chung, Choon Hee

    2014-01-01

    Objective Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes. Research Design and Methods A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentra...

  2. Aspects of Regulation of GFR and Tubular Function in the Diabetic Kidney : Roles of Adenosine, Nitric Oxide and Oxidative Stress

    OpenAIRE

    Persson, Patrik

    2013-01-01

    Diabetic nephropathy is the main cause for initiation of renal replacement therapy and early symptoms in patients include increased glomerular filtration rate (GFR), decreased oxygen tension and albuminuria, followed by a progressive decline in GFR and loss of kidney function. Experimental models of diabetes display increased GFR, decreased tissue oxygenation and nitric oxide bioavailability. These findings are likely to be intertwined in a mechanistic pathway to kidney damage and this thesis...

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

    OpenAIRE

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

    2013-01-01

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

  4. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage

    OpenAIRE

    Muller, Dominik N.; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin

    2002-01-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood p...

  5. 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...

  6. Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease : a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study

    OpenAIRE

    Pugliese, G.; A. Solini; Bonora, E.; ORSI, E.; G. Zerbin; C. Fondelli; Gruden, G; Cavalot, F.; O. Lamacchia; Trevisan, R; Vedovato, M.; G. Penno; RIACE Study Group.

    2014-01-01

    Background The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF’s KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from ca...

  7. Impaired renal function in relatives of chronic kidney disease patients

    OpenAIRE

    Pradip Kumar Dutta; Md Shafiul Haider; Abul Kashem

    2015-01-01

    Background: Chronic kidney disease (CKD) is now a public health burden. If simple screening tests like the glomerular filtration rate (GFR) and presence of albuminuria are done in asymptomatic persons, CKD can be diagnosed earlier that will help in halting the disease and not let it progress to end-stage renal disease (ESRD). Aim: This study was conducted to see the proportion of renal function abnormality in the relatives of CKD patients. Settings and Design: This was a cross-sectional compa...

  8. Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population

    OpenAIRE

    Hernandez, Domingo; Espejo-Gil, Ana; Bernal-Lopez, M. Rosa; Mancera-Romero, Jose; Baca-Osorio, Antonio J; Tinahones, Francisco J; Armas-Padron, Ana M; Ruiz-Esteban, Pedro; torres, Armando; Gomez-Huelgas, Ricardo

    2013-01-01

    Background Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD). Methods A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine s...

  9. The Total Urine Protein-to-Creatinine Ratio Can Predict the Presence of Microalbuminuria

    OpenAIRE

    Yamamoto, Kyoko; Yamamoto, Hiroyuki; Yoshida, Katsumi; Niwa, Koichiro; Nishi, Yutaro; Mizuno, Atsushi; Kuwabara, Masanari; Asano, Taku; Sakoda, Kunihiro; Niinuma, Hiroyuki; Nakahara, Fumiko; Takeda, Kyoko; Shindoh, Chiyohiko; Komatsu, Yasuhiro

    2014-01-01

    Background The Kidney Disease: Improving Global Outcomes chronic kidney disease (CKD) guidelines recommend that CKD be classified based on the etiology, glomerular filtration rate (GFR) and degree of albuminuria. The present study aimed to establish a method that predicts the presence of microalbuminuria by measuring the total urine protein-to-creatinine ratio (TPCR) in patients with cardiovascular disease (CVD) risk factors. Methods and Results We obtained urine samples from 1,033 patients w...

  10. Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

    OpenAIRE

    Penno, Giuseppe; Solini, Anna; Zoppini, Giacomo; Orsi, Emanuela; Fondelli, Cecilia; Zerbini, Gianpaolo; Morano, Susanna; Cavalot, Franco; Lamacchia, Olga; Trevisan, Roberto; Vedovato, Monica; Pugliese, Giuseppe

    2013-01-01

    Background Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficie...

  11. Urine proteome in animals of veterinary interest: species comparison and new biomarkers of nephropathy

    OpenAIRE

    Ferlizza, Enea

    2015-01-01

    Urine is considered an ideal source of biomarkers, however in veterinary medicine a complete study on the urine proteome is still lacking. The present work aimed to apply proteomic techniques to the separation of the urine proteome in dogs, cats, horses, cows and some non-conventional species. High resolution electrophoresis (HRE) was also validated for the quantification of albuminuria in dogs and cats. In healthy cats, applying SDS-PAGE and 2DE coupled to mass spectrometry (MS), was pro...

  12. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

    OpenAIRE

    Hathaway, Catherine K.; Chang, Albert S.; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J.; Bagnell, C. Robert; Jennette, J. Charles; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    About one-third of patients with type 1 diabetes mellitus develop nephropathy, which often progresses to end-stage renal diseases. The present study demonstrates that below-normal Elmo1 expression in mice ameliorates the albuminuria and glomerular histological changes resulting from long-standing type 1 diabetes, whereas above-normal Elmo1 expression makes both worse. Increasing Elmo1 expression leads to aggravation of oxidative stress markers and enhances the expression of fibrogenic genes. ...

  13. A Comparative Study of Clinical Utility of Spot Urine Samples with 24-h Urine Albumin Excretion for Screening of Microalbuminuria in Type 2 Diabetic Patients

    OpenAIRE

    Chavan, Vilas U.; Durgawale, Pushpa P.; Sayyed, Anjum K.; Sontakke, Ajit V.; Attar, Nazir R.; Patel, Swati B.; Patil, Sangita R.; Nilakhe, Shreyasprasad D.

    2011-01-01

    Twenty-four hour urinary albumin excretion (UAE) is considered as gold standard method for albuminuria measurement, but collection of 24-h urine is inconvenient. The aim of present study was to evaluate whether albumin: creatinine ratio (ACR) and urinary albumin concentration (UAC) in different spot urine samples correlate or not with 24-h UAE for screening of microalbuminuria in type 2 diabetic patients. We collected first morning void (FMV), random urine sample (RUS) and 24-h urine, separat...

  14. The renoprotective effects of sulodexide

    OpenAIRE

    Olde Engberink RH; Vogt L

    2016-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

  16. Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria

    OpenAIRE

    Adler, Sharon G.; Schwartz, Sherwyn; Williams, Mark E; Arauz-Pacheco, Carlos; Bolton, Warren K.; Lee, Tyson; Li, Dongxia; Neff, Thomas B.; Urquilla, Pedro R.; Sewell, K. Lea

    2010-01-01

    Background and objectives: This report summarizes the first phase 1 trial treating patients with microalbuminuric diabetic kidney disease (DKD) using FG-3019, a human monoclonal antibody to connective tissue growth factor (CTGF). CTGF is critically involved in processes of progressive fibrosis, including DKD. This phase 1, open-label, dose-escalation trial evaluated safety, pharmacokinetics, and possible therapeutic effects of FG-3019 on albuminuria, proteinuria, and tubular proteins.

  17. Peripheral Neuropathy and VIth Nerve Palsy Related to Randall Disease Successfully Treated by High-Dose Melphalan, Autologous Blood Stem Cell Transplantation, and VIth Nerve Decompression Surgery

    OpenAIRE

    J.-L. Dupond; Manckoundia, P.; Pfitzenmeyer, P; C. Foguem

    2010-01-01

    Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Benc...

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    1989-01-01

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

  2. Microalbuminuria: a Cardiovascular Risk Factor

    OpenAIRE

    ERCAN, Ertuğrul

    2010-01-01

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

  3. Impaired renal function in relatives of chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Pradip Kumar Dutta

    2015-01-01

    Full Text Available Background: Chronic kidney disease (CKD is now a public health burden. If simple screening tests like the glomerular filtration rate (GFR and presence of albuminuria are done in asymptomatic persons, CKD can be diagnosed earlier that will help in halting the disease and not let it progress to end-stage renal disease (ESRD. Aim: This study was conducted to see the proportion of renal function abnormality in the relatives of CKD patients. Settings and Design: This was a cross-sectional comparative study conducted at Chittagong Medical College Hospital (CMCH, Chittagong, Bangladesh, a tertiary hospital in the southern part of Bangladesh. Materials and Methods: We screened the relatives of CKD patients, as a risk population, by urine albumin and estimated GFR (eGFR. Results: We observed a significant difference in urine albumin (29% vs 10% in relatives and nonrelatives, respectively and abnormal renal function [albuminuria/creatinine clearance (CCr criteria] (30% vs 11% in relatives and nonrelatives, respectively between relatives and nonrelatives. Relatives of glomerulonephritis-CKD (GN-CKD patients had more albuminuria than others. Risk factors like hypertension (HTN, impaired glucose tolerance (IGT/diabetes mellitus (DM, and family history of DM/HTN/cardiovascular disease (CVD were significant among relatives and might have some link to familial influence on developing CKD. Conclusion: Relatives of CKD patients should be screened as a risk population to evaluate abnormal renal function.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Qing-Lin Lou

    2012-12-01

    Full Text Available BackgroundTo determine the frequency of chronic kidney disease (CKD and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.MethodsPatients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.ResultsWe recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years. The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval being 1.93 (1.28 to 2.93, 1.70 (1.09 to 2.64, and 1.03 (1.00 to 1.06, respectively.ConclusionIn conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

  9. Impact of ethnicity on progress of glycaemic control in 131 935 newly diagnosed patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register

    Science.gov (United States)

    Svensson, Ann-Marie; Rosengren, Annika; Zethelius, Björn; Eliasson, Björn; Gudbjörnsdottir, Soffia

    2015-01-01

    Objectives Studies on ethnic disparities in glycaemic control have been contradictory, and compromised by excessively broad categories of ethnicity and inadequate adjustment for socioeconomic differences. We aimed to study the effect of ethnicity on glycaemic control in a large cohort of patients with type 2 diabetes. Setting We used nationwide data (mainly from primary care) from the Swedish National Diabetes Register (2002–2011) to identify patients with newly diagnosed (within 12 months) type 2 diabetes. Participants We included 131 935 patients (with 713 495 appointments), representing 10 ethnic groups, who were followed up to 10 years. Primary and secondary outcome measures Progress of glycated haemoglobin (HbA1c) for up to 10 years was examined. Mixed models were used to correlate ethnicity with HbA1c (mmol/mol). The effect of glycaemic disparities was examined by assessing the risk of developing albuminuria. The impact of ethnicity was compared to that of income, education and physical activity. Results Immigrants, particularly those of non-Western origin, received glucose-lowering therapy earlier, had 30% more appointments but displayed poorer glycaemic control (2–5 mmol/mol higher HbA1c than native Swedes). Probability of therapy failure was 28–111% higher for non-Western groups than for native Swedes. High-income Western groups remained below the target-level of HbA1c for 4–5 years, whereas non-Western populations never reached the target level. These disparities translated into 51–92% higher risk of developing albuminuria. The impact of ethnicity was greater than the effect of income and education, and equal to the effect of physical activity. Conclusions Despite earlier pharmacological treatment and more frequent appointments, immigrants of non-Western origin display poorer glycaemic control and this is mirrored in a higher risk of developing albuminuria. PMID:26048210

  10. Diabetic Kidney Disease in FVB/NJ Akita Mice: Temporal Pattern of Kidney Injury and Urinary Nephrin Excretion

    Science.gov (United States)

    Chang, Jae-Hyung; Paik, Seung-Yeol; Mao, Lan; Eisner, William; Flannery, Patrick J.; Wang, Liming; Tang, Yuping; Mattocks, Natalie; Hadjadj, Samy; Goujon, Jean-Michel; Ruiz, Phillip; Gurley, Susan B.; Spurney, Robert F.

    2012-01-01

    Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process. PMID:22496773

  11. Early chronic kidney disease in Aboriginal and non-Aboriginal Australian children: remoteness, socioeconomic disadvantage or race?

    Science.gov (United States)

    Haysom, L; Williams, R; Hodson, E; Roy, L P; Lyle, D; Craig, J C

    2007-04-01

    Indigenous people suffer substantially more end-stage kidney disease (ESKD), especially Australian Aboriginals. Previous work suggests causal pathways beginning early in life. No studies have shown the prevalence of early markers of chronic kidney disease (CKD) in both Indigenous and non-Indigenous children or the association with environmental health determinants--geographic remoteness and socioeconomic disadvantage. Height, weight, blood pressure, and urinary abnormalities were measured in age- and gender-matched Aboriginal and non-Aboriginal children from elementary schools across diverse areas of New South Wales, Australia. Hematuria was defined as>or=25 red blood cells/microl (>or=1+), proteinuria>or=0.30 g/l (>or=1+), and albuminuria (by albumin:creatinine)>or=3.4 mg/mmol. Remoteness and socioeconomic status were assigned using the Accessibility and Remoteness Index of Australia and Socio-Economic Indexes For Areas. From 2002 to 2004, 2266 children (55% Aboriginal, mean age 8.9 years) were enrolled from 37 elementary schools. Overall prevalence of hematuria was 5.5%, proteinuria 7.3%, and albuminuria 7.3%. Only baseline hematuria was more common in Aboriginal children (7.1 versus 3.6%; P=0.002). At 2-year follow-up, 1.2% of Aboriginal children had persistent hematuria that was no different from non-Aboriginal children (P=0.60). Socioeconomic disadvantage and geographical isolation were neither significant nor consistent risk factors for any marker of CKD. Aboriginal children have no increase in albuminuria, proteinuria, or persistent hematuria, which are more important markers for CKD. This suggests ESKD in Aboriginal people may be preventable during early adult life. PMID:17311073

  12. 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.

  13. 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

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

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    Glenn Kimberly

    2011-05-01

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

  15. 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.

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-11-15

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

  18. Comparative study of amlodipine versus ramipril and their effects on markers of renal disease in type 2 diabetes mellitus

    OpenAIRE

    Raj Kumar; KMDS Panag; Kavita Paul; Kamlesh Kohli; H. L. Kazal

    2016-01-01

    Background: Diabetes mellitus is a chronic metabolic condition and patients require long treatment for it. The aim of the study was to evaluate the effects of amlodipine and ramipril on the blood pressure and markers of renal disease (viz. serum creatinine, albuminuria and eGFR) in type 2 diabetes mellitus. Methods: This was a randomized, open labelled, parallel study conducted to assess the effect of Amlodipine (2.5-10 mg) and Ramipril (2.5-10 mg) daily for 24 weeks in T2DM patients (n=10...

  19. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Schievink, B; Kröpelin, T; Mulder, S; Parving, H-H; Remuzzi, G; Dwyer, J; Vemer, P; de Zeeuw, D; Lambers Heerspink, H J

    2016-01-01

    the BENEDICT, IRMA-2, RENAAL and IDNT trials that assessed effects of RAS intervention in patients with type 2 diabetes. We built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (eGFR). Using survival analyses, we assessed the effect of RAS......AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from...

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

    OpenAIRE

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

    2013-01-01

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

  1. Derivation and Validation of a New Cardiovascular Risk Score for People With Type 2 Diabetes

    OpenAIRE

    Elley, C. Raina; Robinson, Elizabeth; Kenealy, Tim; Bramley, Dale; Drury, Paul L

    2010-01-01

    OBJECTIVE To derive a 5-year cardiovascular disease (CVD) risk equation from usual-care data that is appropriate for people with type 2 diabetes from a wide range of ethnic groups, variable glycemic control, and high rates of albuminuria in New Zealand. RESEARCH DESIGN AND METHODS This prospective open-cohort study used primary-care data from 36,127 people with type 2 diabetes without previous CVD to derive a CVD equation using Cox proportional hazards regression models. Data from 12,626 peop...

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

    DEFF Research Database (Denmark)

    Jensen, T; Richter, E A; Feldt-Rasmussen, B;

    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 or the...

  3. 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-

  4. Assessment of Renal Pathology and Dysfunction in Pediatric Patients with Fabry Disease

    Science.gov (United States)

    Ramaswami, Uma; Najafian, Behzad; Schieppati, Arrigo; Mauer, Michael; Bichet, Daniel G.

    2016-01-01

    Overt renal disease often first presents in males with Fabry disease in early-to-mid adulthood, but proteinuria and reduced glomerular filtration rate may occur in adolescents and in young children. More recently, kidney biopsy data have shown early renal histological changes in pediatric patients. Renal investigations and their timing in children remain poorly defined. A consensus on renal investigations is necessary to understand the natural progression of the disease and to evaluate the efficacy of treatments such as enzyme replacement therapies. This manuscript addresses three main categories, including the use of glomerular filtration rates, measuring albuminuria and renal biopsies in children. PMID:20056758

  5. 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

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

    OpenAIRE

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Packham, David K; Wolfe, Rory; Reutens, Anne T; Berl, Tomas; Heerspink, Hiddo Lambers; Rohde, Richard; Ivory, Sara; Lewis, Julia; Raz, Itamar; Wiegmann, Thomas B; Chan, Juliana C N; de Zeeuw, Dick; Lewis, Edmund J; Atkins, Robert C; Thorsteinsson, Birger

    2012-01-01

    -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 of......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...... diabetes, renal impairment, and macroalbuminuria....

  8. Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

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    Antonio V Gaddi

    2010-07-01

    Full Text Available Antonio V Gaddi1, Arrigo FG Cicero1, Giovanni Gambaro21Atherosclerosis and Metabolic disease Research Unit, Internal Medicine, Aging and Kidney diseases Dept., University of Bologna, Italy; 2Nephrology and Dialysis Unit, Gemelli University Hospital, Sacred Heart Catholic University, Rome, ItalyAbstract: A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin–angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment.Keywords: glycosaminoglycans, sulodexide, albuminuria, proteinuria, diabetic nephropathy

  9. Nephrotoxicity of cadmium & lead.

    Science.gov (United States)

    Gonick, H C

    2008-10-01

    Cadmium and lead are divalent cations with a propensity to settle in the proximal tubule of the nephron, leading to nephrotoxicity. The pathophysiological results, however, tend to diverge. Cadmium in sufficient cumulative dosage leads to the production of the Fanconi syndrome, a generalized proximal tubular reabsorptive defect thought to be related to inhibition of both ATP production and Na-K-ATPase activity. On the other hand, lead accumulation in the proximal tubule leads to hyperuricaemia and gout, presumably by inhibiting uric acid secretion, and diminished glomerular filteration rate (GFR). Fanconi syndrome is seen unusually only in children and experimental animals. Cadmium nephrotoxicity is heralded by increased excretion of beta2-microglobulin, retinol binding protein and alpha1-microglobulin, indicative of decreased proximal tubule function. Beta2-microglobulinuria is not found in lead nephropathy. In lead nephropathy albuminuria is absent or minimal whereas in cadmium nephropathy albuminuria is variable. From the standpoint of pathology, both entities are characterized by tubulointerstitial disease and fibrosis, but only early lead nephropathy is characterized by the presence of proximal tubule nuclear inclusion bodies, due to the combination of lead with a lead binding-protein. PMID:19106433

  10. Th1 and Th17 cells induce proliferative glomerulonephritis.

    Science.gov (United States)

    Summers, Shaun A; Steinmetz, Oliver M; Li, Ming; Kausman, Joshua Y; Semple, Timothy; Edgtton, Kristy L; Borza, Dorin-Bogdan; Braley, Hal; Holdsworth, Stephen R; Kitching, A Richard

    2009-12-01

    Th1 effector CD4+ cells contribute to the pathogenesis of proliferative and crescentic glomerulonephritis, but whether effector Th17 cells also contribute is unknown. We compared the involvement of Th1 and Th17 cells in a mouse model of antigen-specific glomerulonephritis in which effector CD4+ cells are the only components of adaptive immunity that induce injury. We planted the antigen ovalbumin on the glomerular basement membrane of Rag1(-/-) mice using an ovalbumin-conjugated non-nephritogenic IgG1 monoclonal antibody against alpha3(IV) collagen. Subsequent injection of either Th1- or Th17-polarized ovalbumin-specific CD4+ effector cells induced proliferative glomerulonephritis. Mice injected with Th1 cells developed progressive albuminuria over 21 d, histologic injury including 5.5 +/- 0.9% crescent formation/segmental necrosis, elevated urinary nitrate, and increased renal NOS2, CCL2, and CCL5 mRNA. Mice injected with Th17 cells developed albuminuria by 3 d; compared with Th1-injected mice, their glomeruli contained more neutrophils and greater expression of renal CXCL1 mRNA. In conclusion, Th1 and Th17 effector cells can induce glomerular injury. Understanding how these two subsets mediate proliferative forms of glomerulonephritis may lead to targeted therapies. PMID:19820122

  11. 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.

  12. 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.

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

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    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

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

  14. Can we target tubular damage to prevent renal function decline in diabetes?

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    Bonventre, Joseph V

    2012-09-01

    The glomerulus has been at the center of attention as the primary site of injury in diabetic nephropathy (DN). Although there is no question that there are changes seen in the glomerulus, it is also well known that tubulointerstitial changes are a prominent component of the disease, especially in patients with type 2 diabetes. The level of albuminuria and DN disease progression best correlate with tubular degeneration and interstitial fibrosis. Nephrotoxicity studies in animals reveal that albuminuria is a highly sensitive marker of early tubular toxicity even in the absence of glomerular pathology. Urinary biomarker data in human beings support the view that proximal tubule injury contributes in a primary way, rather than in a secondary manner, to the development of early DN. I present a model in which very specific injury to the proximal tubule in vivo in the mouse results in severe inflammation, loss of blood vessels, interstitial fibrosis, and glomerulosclerosis. Increased glucose levels, free glycation adducts, reactive oxygen species, and oxidized lipids result in toxicity to tubule epithelia. This results in loss of cells with a stimulus to repair the epithelium. However, because of sublethal injury there is cell-cycle arrest in epithelial cells attempting to replace damaged cells. This leads to epithelial secretion of both profibrogenic growth factors, collagens, and factors that cause pericytes to proliferate and differentiate into myofibroblasts, leading to endothelial destabilization and capillary rarefaction. Local ischemia ensues with further injury to the tubules, more profibrogenic mediators, matrix protein deposition, fibrosis, and glomerulosclerosis. PMID:23062986

  15. Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria

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    Jauregui, Alexandra; Mintz, Daniel H; Mundel, Peter; Fornoni, Alessia

    2010-01-01

    Purpose of review In diabetic nephropathy (DN), insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of DN will be discussed. Recent findings While normal podocytes uptake glucose in response to insulin, diabetic podocytes become insulin resistant in experimental DN prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independently of their systemic effects on the metabolic control of diabetes. Summary We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of DN in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of DN. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of DN. Understanding the role of podocyte in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of DN, it may affect current strategies for prevention and treatment of DN, and it may allow for the identification of novel therapeutic targets. PMID:19724224

  16. Proteomic identification of vanin-1 as a marker of kidney damage in a rat model of type 1 diabetic nephropathy.

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    Fugmann, Tim; Borgia, Beatrice; Révész, Csaba; Godó, Mária; Forsblom, Carol; Hamar, Peter; Holthöfer, Harry; Neri, Dario; Roesli, Christoph

    2011-08-01

    At present, the urinary albumin excretion rate is the best noninvasive predictor for diabetic nephropathy (DN) but major limitations are associated with this marker. Here, we used in vivo perfusion technology to establish disease progression markers in an animal model of DN. Rats were perfused with a reactive ester derivative of biotin at various times after streptozotocin treatment. Following homogenization of kidney tissue and affinity purification of biotinylated proteins, a label-free mass spectrometry-based proteomic analysis of tryptic digests identified and relatively quantified 396 proteins. Of these proteins, 24 and 11 were found to be more than 10-fold up- or downregulated, respectively, compared with the same procedure in vehicle-treated rats. Changes in the expression of selected differentially regulated proteins were validated by immunofluorescence detection in kidney tissue from control and diabetic rats. Immunoblot analysis of pooled human urine found that concentrations of vanin-1, an ectoenzyme pantetheinase, distinguished diabetic patients with macroalbuminuria from those with normal albuminuria. Uromodulin was elevated in the urine pools of the diabetic patients, regardless of the degree of albuminuria, compared with healthy controls. Thus, in vivo biotinylation facilitates the detection of disease-specific changes in the abundance of potential biomarker proteins for disease monitoring and/or pharmacodelivery applications. PMID:21544065

  17. Mining the genome for susceptibility to diabetic nephropathy: the role of large-scale studies and consortia.

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    Iyengar, Sudha K; Freedman, Barry I; Sedor, John R

    2007-03-01

    Approximately 30% of individuals with type 1 and type 2 diabetes develop persistent albuminuria, lose renal function, and are at increased risk for cardiovascular and other microvascular complications. Diabetes and kidney diseases rank within the top 10 causes of death in Westernized countries and cause significant morbidity. Given these observations, genetic, genomic, and proteomic investigations have been initiated to better define basic mechanisms for disease initiation and progression, to identify individuals at risk for diabetic complications, and to develop more efficacious therapies. In this review we have focused on linkage analyses of candidate genes or chromosomal regions, or coarse genome-wide scans, which have mapped either categorical (chronic kidney disease or end-stage renal disease) or quantitative kidney traits (albuminuria/proteinuria or glomerular filtration rate). Most loci identified to date have not been replicated, however, several linked chromosomal regions are concordant between independent samples, suggesting the presence of a diabetic nephropathy gene. Two genes, carnosinase (CNDP1) on 18q, and engulfment and cell motility 1 (ELMO1) on 7p14, have been identified as diabetic nephropathy susceptibility genes, but these results require authentication. The availability of patient data sets with large sample sizes, improvements in informatics, genotyping technology, and statistical methodologies should accelerate the discovery of valid diabetic nephropathy susceptibility genes. PMID:17418689

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

    Science.gov (United States)

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

    2006-11-01

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

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

    Science.gov (United States)

    Wong, Chee Wai; Teo, Boon Wee; Lamoureux, Ecosse; Ikram, Mohammad Kamran; Wang, Jie Jin; Tai, E. Shyong; Sethi, Sunil; Wong, Tien Yin; Sabanayagam, Charumathi

    2015-01-01

    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. PMID:26576434

  20. 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.

  1. Clinical significance of combined detection of serum CRP, IL-6, IL-8 and TNF-α levels for diagnosis of type 2 diabetic nephropathy

    International Nuclear Information System (INIS)

    Objective: To investigate the significance of changes of serum CRP, IL-6, IL-8 and TNF-α levels in the development of nephropathy in patients with type 2 diabetic nephrosis. Methods: Serum CRP, IL-6, IL-8 and TNF-α levels were measured with RIA in 112 patients with DM2 and 30 controls. The 112 diabetic patients fell into three groups: (1) Group A: without albuminuria (urine albumin excretion rate UAER200 μg/min, n=34). Results: Serum levels of CRP, IL-6, IL-8 and TNF were significantly higher in all the patients with type 2 diabetes than those in controls (P<0.01). Serum levels of CRP, IL-6, IL-8 and TNF were significantly higher in DM patients with microalbminuria than those in patients without albuminuria (P<0.01). Serum levels of CRP, IL-6, IL-8 and TNF were significantly higher in diabetic patients with macroalbumlnuria than those in patients with microalbuminuria (P<0.01). Conclusion: Determination of serum TNF-α, IL-6 and IL-8 levels might be helpful for early detection of diabetic nephropathy and monitoring the progress of the disease process. (authors)

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

    Science.gov (United States)

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

    2015-09-01

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

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

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    S. V. Malchikova

    2009-01-01

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

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

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    S. V. Malchikova

    2016-01-01

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

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

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    Eddy, A.A.; McCulloch, L.; Liu, E.; Adams, J. (Hospital for Sick Children, Toronto, ON (Canada))

    1991-05-01

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

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

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

    2014-03-03

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

  7. The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes

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    Hyun Hee Chung

    2013-04-01

    Full Text Available BackgroundRecently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C, albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes.MethodsWe enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day and we compared cancer incidence using analysis of covariance.ResultsLDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574. In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day (P=0.00.ConclusionThese results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. Síndrome metabólico en un grupo de pacientes diabéticos tipo 1. ¿Una nueva variedad de diabetes?

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    María Soledad Báez

    2009-07-01

    Full Text Available Background: Metabolic Syndrome (MS is related to insulin resistance and to type 2 diabetes mellitus. However, patients with type 1 diabetes mellitus (T1DM may also develop this condition. Aim: To determine the prevalence of MS in patients with T1DM. Material and methods: Cross sectional study of 52 patients with T1DM aged 18 to 72 years (27 females with 5 years or more since their diagnosis of T1DM. MS presence was defined according to the Adult Treatment Panel III criteria. Acanthosis nigricans (AN, waist circumference (WC, daily dose of insulin, glycosylated hemoglobin (HbAlc and micro albuminuria were evaluated. Results: The prevalence of MS was 25% (13/52. A higher daily dose of insulin was required in patients with MS (p =0.018, with AN (p =0.022 and with obesity (p =0.002. A direct association between WC and the dose of insulin was observed (r =0.51; p <0.0001. No association was observed between MS, time of evolution of T1DM, HbAlc or micro albuminuria. Conclusions: In this group of patients with T1DM there was a high prevalence of MS.

  12. Síndrome metabólico en un grupo de pacientes diabéticos tipo 1. ¿Una nueva variedad de diabetes? Presence of metabolic syndrome among patients with type 1 diabetes mellitus

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    María Soledad Báez

    2009-07-01

    Full Text Available Background: Metabolic Syndrome (MS is related to insulin resistance and to type 2 diabetes mellitus. However, patients with type 1 diabetes mellitus (T1DM may also develop this condition. Aim: To determine the prevalence of MS in patients with T1DM. Material and methods: Cross sectional study of 52 patients with T1DM aged 18 to 72 years (27 females with 5 years or more since their diagnosis of T1DM. MS presence was defined according to the Adult Treatment Panel III criteria. Acanthosis nigricans (AN, waist circumference (WC, daily dose of insulin, glycosylated hemoglobin (HbAlc and micro albuminuria were evaluated. Results: The prevalence of MS was 25% (13/52. A higher daily dose of insulin was required in patients with MS (p =0.018, with AN (p =0.022 and with obesity (p =0.002. A direct association between WC and the dose of insulin was observed (r =0.51; p <0.0001. No association was observed between MS, time of evolution of T1DM, HbAlc or micro albuminuria. Conclusions: In this group of patients with T1DM there was a high prevalence of MS.

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

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    Junghyun Kim

    2012-01-01

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

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

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    Daqing Hong

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

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

    Directory of Open Access Journals (Sweden)

    Miguel A Salinero-Fort

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

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

    International Nuclear Information System (INIS)

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

  17. 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 (

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Urinary gamma-glutamyl transferase (GGT) as a marker of tubular proteinuria in dogs with canine leishmaniasis, using sodium dodecylsulphate (SDS) electrophoresis as a reference method.

    Science.gov (United States)

    Ibba, F; Mangiagalli, G; Paltrinieri, S

    2016-04-01

    In order to assess if urinary γ- glutamyl transferase (GGT) identify tubular proteinuria in leishmaniotic dogs, the GGT/urinary creatinine (UC) ratio was calculated in 39 leishmaniotic dogs. According to sodium dodecylsulphate-agarose gel electrophoresis, the dogs had albuminuria (A, n = 10), glomerular (G, n = 3), tubular (T, n = 4) or mixed proteinuria (M, n = 22). The median GGT/UC ratio was 0.3, 0.3, 2.2, and 7.5, in groups G, A, M, and T, respectively. Statistically significant differences were found between groups G and M (P = 0.002), G and T (P GGT/UC values >0.81 or >2.64 could identify dogs in the M/T or T groups, respectively. Therefore, GGT/UC might be useful for the management of leishmaniotic dogs. PMID:26897435

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

    DEFF Research Database (Denmark)

    Lauszus, Finn

    2016-01-01

    high-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....... Studies on these issues suggest 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...... 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...

  1. G/T substitution in intron 1 of the UNC13B gene is associated with increased risk of nephropathy in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Tregouet, D.A.; Groop, P.H.; McGinn, S.; Forsblom, C.; Hadjadj, S.; Marre, M.; Tarnow, L.; Telgmann, R.; Godefroy, T.; Nicaud, V.; Rousseau, R.; Parkkonen, M.; Hoverfalt, A.; Gut, I.; Heath, S.; Matsuda, F.; Cox, R.; Kazeem, G.; Farrall, M.; Gauguier, D.; Brand-Herrmann, S.M.; Cambien, F.; Lathrop, M.; Vionnet, N.; Parving, Hans-Henrik

    2008-01-01

    for association with diabetic nephropathy (persistent albuminuria >/=300 mg/24 h) in a large type 1 diabetes case/control (1,176/1,323) study from three European populations. RESULTS: Only one SNP, rs2281999, located in the UNC13B gene, was significantly associated with nephropathy after correction......OBJECTIVE: Genetic and environmental factors modulate the susceptibility to diabetic nephropathy, as initiating and/or progression factors. The objective of the European Rational Approach for the Genetics of Diabetic Complications (EURAGEDIC) study is to identify nephropathy susceptibility genes....... We report molecular genetic studies for 127 candidate genes for nephropathy. RESEARCH DESIGN AND METHODS: Polymorphisms were identified through sequencing of promoter, exon, and flanking intron gene regions and a database search. A total of 344 nonredundant SNPs and nonsynonymous variants were tested...

  2. 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.

  3. Galectin 3

    DEFF Research Database (Denmark)

    Stoltze Gaborit, Freja; Bosselmann, Helle; Kistorp, Caroline;

    2016-01-01

    Gal-3 reflects echocardiographic measures, neurohumoral activity and renal function. The aim of this study was to evaluate the relationship between plasma concentrations of Gal-3 and neurohumoral activity, myocardial and renal function in patients with HF, including advanced echocardiographic measures...... % (27-39 %) and 30 % were in NYHA class III-IV. RESULTS: Patients with plasma concentrations of Gal-3 above the median had significantly lower estimated glomerular filtration rate (eGFR) and this association remained significant in multivariate regression analysis (β: -0.010; 95 % CI -0.012--0.008; P...... < 0.001), adjusted for age, gender, medical treatment. Plasma concentrations of Gal-3 were not associated with albuminuria (Beta: 0.008; 95 % CI:-0.028-0.045; P = 0.652). There were no association between plasma concentrations of Gal-3 and myocardial function or structure estimated by LVEF, LVmass...

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

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2015-04-01

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

  5. 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...... injection 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...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    AIM: To describe the incidence, clinical presentation and paraclinical findings in childhood sarcoidosis in Denmark, 1979-1994. METHODS: Patients (n = 5536) with a diagnosis of sarcoidosis were drawn from the nationwide Patient Registry; 81 patients were < or = 15 y of age. The diagnosis of...... sarcoidosis was reconfirmed in 48/81 (59%) patients. In 35/48 (73%) patients, diagnosis was verified by histology, and in 13 it was substantiated by paraclinical/clinical findings. RESULTS: The series comprised 26 boys and 22 girls (male/female ratio 1.18). Median age at diagnosis was 13 y (range 0.7-15). In...... examination (glucose, albumin, haemoglobin) was normal in 96% of the patients; the patient with nephrocalcinosis had albuminuria and haematuria. CONCLUSION: The incidence of sarcoidosis in Danish children is low and increases with age. Sarcoidosis in young children may present clinical features that are...

  7. 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...

  8. 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...

  9. Exenatide induced acute kidney injury.

    Science.gov (United States)

    Aijazi, Ishma; Abdulla, Fadhil M; Zuberi, Beyla J; Elhassan, Ahmed

    2014-01-01

    Exenatide is an incretin mimetic. It was approved by the federal drug authority in 2005 for the treatment of type-2 diabetes. Since it is a relatively new medicine clinicians have limited experience with regards to its side effects and safety profile. We report a 47 year old lady who presented with exenatide associated acute kidney injury. She had type-2 diabetes for 10 years with mild micro albuminuria and normal renal functions. She was also taking a stable dose of metformin, gliclazide, angiotensin converting enzyme inhibitor and diuretic for over a year and there was no history of any recent use of non-steroid anti-inflammatory medications. One week after starting exenatide, she developed severe vomiting, followed by hypotension. She presented with acute renal insufficiency and severe lactic acidosis and had to be dialyzed on emergency basis. To our knowledge this is probably the first case reported in the local United Arab Emirate (U.A.E) population. PMID:25672206

  10. Telemedicine compared with standard care in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Rasmussen, Ole Winther; Lauszus, Finn; Loekke, M

    2015-01-01

    INTRODUCTION: Good metabolic control is important in type 2 diabetes mellitus to improve quality of life, work ability and life expectancy, and the use of telemedicine has proved efficient as an add-on to the usual treatment. However, few studies in type 2 diabetes patients have directly compared...... telemedicine with conventional outpatient treatment, and we wanted to evaluate whether telemedicine, compared with standard care, provides equivalent clinical outcomes. METHODS: Forty patients with type 2 diabetes mellitus allocated from October 2011-July 2012 were randomized to either treatment at home by...... video conferences only or standard outpatient treatment. Primary outcomes were HbA1c and blood glucose levels and secondary outcomes were 24-hour blood pressure, cholesterol levels and albuminuria. The video-telephone was a broadband solution installed and serviced by the Danish Telephone Company (TDC...

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

    Science.gov (United States)

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

    2001-01-01

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

  12. 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

    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 in......BACKGROUND/AIMS: Microalbuminuria is associated with diabetes and is an independent risk factor for developing diabetic nephropathy. We have previously reported the overall prevalence of normoalbuminuria, microalbuminuria, and macroalbuminuria to be 51, 39, and 9.8%, respectively, in an unselected...... population of patients with type 2 diabetes. Renal dysfunction was present in a large proportion of these patients without proteinuria, assessed by a single random albumin-to-creatinine ratio (ACR). We therefore undertook to characterize the nature of this association of non-proteinuric renal dysfunction in...

  13. Angiopoietins and diabetic nephropathy.

    Science.gov (United States)

    Gnudi, Luigi

    2016-08-01

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

  14. Application of serum TGF-β1 determination for early diagnosis of diabetic nephropathy

    International Nuclear Information System (INIS)

    Objective: To investigate the feasibility of obtaining early diagnosis of diabetic nephropathy (DN) with determination of serum transforming growth factor-β1 (TGF- β1 ). Methods: Serum TGF-β1 (with ELISA) and β2-microglobulin (β2-m, with RIA) levels as well as urinany β2-m, albumin and mciro-amount of proteins were determined in 35 controls and 84 diabetic patients with different degrees of albuminuria (Group A: urinary albumin excretion UAE 300mg/24h, n=28). Results: The serum TGF-β1, β2-m and urinary β2-m contents were correlated well with UAE in the diabetic patients. Conclusion: TGF-β1 and β2-m were sensitive markers for early renal function injury in diabetic patients and determination of serum TGF-β1 levels was clinically useful for diagnosis of early DN. (authors)

  15. YKL-40--an emerging biomarker in cardiovascular disease and diabetes

    DEFF Research Database (Denmark)

    Rathcke, Camilla N; Vestergaard, Henrik

    2009-01-01

    . Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated...... with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating...... YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial...

  16. 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

    control in T1DM patients without known heart disease was examined. METHODS: Cross-sectional study of 1093 T1DM patients from the outpatient clinic at Steno Diabetes Center. Physical examination, questionnaires, and echocardiography were performed in all patients. Investigators were blinded to all...... 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...... impaired glycemic control. A causal relationship cannot be determined from this study. Given the benefit on cardiovascular outcome, this should not cause patients to stop statin treatment, but may indicate a need to revisit dose of insulin when starting statin treatment....

  17. European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy

    DEFF Research Database (Denmark)

    Tarnow, L.; Groop, P.H.; Hadjadj, S.;

    2008-01-01

    was performed by direct sequencing. RESULTS: In total, 1176 cases with diabetic nephropathy and 1323 diabetic controls with longstanding normoalbuminuria were included from three European populations (Denmark, Finland, France). Data were collected on HbA(1c), blood pressure, urinary albumin excretion rate......BACKGROUND: Diabetic nephropathy is likely to be a complex genetic trait. To date, most diabetic nephropathy candidate gene studies have tested a limited number of genes and variants in small sized populations, or in populations that were poorly matched or phenotyped. The main objective...... of the EURAGEDIC study was to address these problems. METHODS: Single nucleotide polymorphisms (SNPs) in candidate genes were tested for association with overt diabetic nephropathy (persistent albuminuria >300 mg/24 h) in a large (n=2499) Type 1 diabetes case/control study. Testing for transmission disequilibrium...

  18. 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.

  19. 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.

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

    Science.gov (United States)

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

    2007-09-01

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

  1. 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; Fuller, John; Klein, Ronald; Orchard, Trevor; Porta, Massimo; Parving, Hans-Henrik

    2009-01-01

    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......, caregivers, and researchers were blinded to treatment assignment. During a median follow-up of 4.7 years, 793 patients discontinued therapy and 63 were lost to follow-up. MEASUREMENTS: Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 microg/min or greater, then 2...

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

  3. 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......INTRODUCTION: Vitamin D may ameliorate hypertension and kidney disease through genomic and extra-genomic pathways. OBJECTIVE: To investigate the impact of vitamin D in a transgenic rat model of angiotensin II-mediated hypertensive organ failure. METHODS: In 4-week-old age-matched rats...... 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...

  4. Asymptomatic coronary artery disease in Type-2 diabetes

    International Nuclear Information System (INIS)

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

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

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    Anubhav Thukral

    2011-01-01

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

  6. 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

  7. Neonatal Fc receptor promotes immune complex-mediated glomerular disease.

    Science.gov (United States)

    Olaru, Florina; Luo, Wentian; Suleiman, Hani; St John, Patricia L; Ge, Linna; Mezo, Adam R; Shaw, Andrey S; Abrahamson, Dale R; Miner, Jeffrey H; Borza, Dorin-Bogdan

    2014-05-01

    The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex-mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex-mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG. PMID:24357670

  8. A STUDY OF MICROALBUMINURIA IN ESSENTIAL HYPERTENSION AND ITS CORRELATION WITH THE TARGET ORGAN DAMAGE

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    Ramakrishna

    2015-12-01

    Full Text Available Hypertension is one of the most common disease afflicting humans throughout the world. Target organ damage resulting from hypertension includes those affecting the brain, heart, kidneys and the eyes. Focal neurological deficits, dyspnoea, chest pain, headache, loss of vision are considered as the commonest symptoms with which patients having hypertension related acute target organ damage present. OBJECTIVES To assess the prevalence of micro-albuminuria among the non-diabetic hypertensive patients and to assess the relationship between micro-albuminuria and target organ damage. MATERIALS AND METHODS A cross-sectional study was conducted in 100 hypertensive patients microalbuminuria was measured in these patients by micral dipstick method. Chi-square test was used to study the relationship between microalbuminuria and other variables. P value was calculated for all the variables. RESULTS The prevalence of microalbuminuria was 23% among the non-diabetic hypertensive patients. A positive correlation between microalbuminuria and target organ damage was found in these patients. The odds ratio for microalbuminuric patients having retinopathy was 8.3% (95% confidence interval 2.4-37.5. Prevalence of microalbuminuria was higher among patients with Cerebrovascular Accidents (P < 0.001 with the odds ratio of 15.3 (95% confidence interval 4.9-47.5 and it was observed that there was significant correlation between the prevalence of microalbuminuria and the presence of LVH (P <0.001 with the odds ratio of 10.4 (95% confidence interval 3.52-30.8 in hypertensive patients. CONCLUSION Microalbuminuria had a statistically significant correlation with the target organ damage. Extensive screening for microalbuminuria is required in hypertensive subjects to assess the cardiovascular risk.

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

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

    2015-10-01

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

  10. Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC

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    Natarajan Rama

    2010-11-01

    Full Text Available Abstract Background Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative properties, and depending upon the experimental circumstances, may be pro- or anti-apoptotic. Many of these biological actions could ameliorate diabetic nephropathy. Methods/Design Mouse podocytes, cultured in basal or high glucose conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX-2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and DNase I assays for F- to G- actin cleavage were performed for in vitro analyses. In vivo studies examined the effects of dietary curcumin on the development of diabetic nephropathy in streptozotocin (Stz-induced diabetes in DBA2J mice. Urinary albumin to creatinine ratios were obtained, high performance liquid chromatography was performed for urinary curcuminoid measurements, and Western blots for p38-MAPK and total HSP25 were performed. Results Curcumin enhanced the phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited the activation of caspase-3 in vitro. In curcumin-treated DBA2J mice with Stz-diabetes, HPLC measurements confirmed the presence of urinary curcuminoid. Nevertheless, dietary provision of curcumin either before or after the induction of diabetes failed to attenuate albuminuria. Conclusions Apart from species, strain, early differences in glycemic control, and/or dosing effects, the failure to modulate albuminuria may have been due to a decrement in renal HSP25 or stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In addition, these studies suggest that timed urine collections may be useful for monitoring curcumin dosing and renal pharmacodynamic effects.

  11. 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.

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

    International Nuclear Information System (INIS)

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

  13. Silent cerebral infarction is associated with the development and progression of nephropathy in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease in patients with diabetes. The relationship between renal manifestations of CKD (albuminuria and decreased glomerular filtration rate) and silent cerebral infarction (SCI) has attracted attention; however, most studies examined the effects of components of CKD on prevalence of SCI. We sought to assess the relationship between SCI and the development and progression of nephropathy in type 2 diabetic patients. We studied 366 type 2 diabetic patients with normoalbuminuria (urinary albumin-to-creatinine ratio [ACR] -1, N=246) or microalbuminuria (ACR=30-299 mg g-1, N=120). SCI was defined by cranial MRI. The primary end point was progression from normo- to microalbuminuria or from micro- to macroalbuminuria. The cumulative incidence of the primary end point was estimated using the Kaplan-Meier method. Risk estimates for reaching the end point were calculated using Cox proportional hazard model analyses. During a median follow-up period of 3.9 years, 23 normoalbuminuric and 24 microalbuminuric patients reached the primary end point. Patients with SCI (N=171) had a greater incidence of reaching the end point than those without SCI (N=195, P=0.020 by the log-rank test), with a hazard ratio of 2.02 (95% confidence interval=1.09-3.72, P=0.025) in the multivariate Cox regression model. Although the common pathogenesis of SCI and albuminuria in diabetic patients is still unclear, SCI may be a predictor of progression of nephropathy in type 2 diabetic patients. (author)

  14. 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. PMID:27053688

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

    Science.gov (United States)

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

    2016-03-01

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

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

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    Moradi S

    2012-01-01

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

  17. 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.

  18. 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.

  19. Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice.

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    Nakamura, Takashi; Murase, Takayo; Nampei, Mai; Morimoto, Nobutaka; Ashizawa, Naoki; Iwanaga, Takashi; Sakamoto, Ryusuke

    2016-06-01

    Topiroxostat, a xanthine oxidoreductase (XOR) inhibitor, has been shown to decrease the urinary albumin-to-creatinine ratio compared with placebo in hyperuricemic patients with stage 3 chronic kidney disease. Thus, we aimed to ascertain the albuminuria-lowering effect of topiroxostat in diabetic mouse. Db/db mice were fed standard diets with or without topiroxostat (0.1, 0.3, 1, and 3mg/kg/day) and febuxostat (0.1, 0.3, and 1mg/kg/day) for four weeks. Urinary albumin and purine bodies levels, XOR activities, and drug concentrations in the liver, kidney, and plasma were measured. Moreover, the XOR inhibitory activity of each XOR inhibitor was evaluated with or without an exogenous protein in vitro. Topiroxostat decreased dose-dependently the urinary albumin excretion, but febuxostat did not show such a tendency. Treatment with topiroxostat inhibited plasma XOR activity with dose-dependent increase in plasma purine levels, which was not observed by febuxostat. Pharmacokinetic/pharmacodynamic analysis revealed that topiroxostat and febuxostat concentration in each tissue showed a good correlation with both the hypouricemic effect and plasma drug concentration, whereas the change in albuminuria correlated neither with the change in uric acid nor with drug concentration in plasma. However, the change in urinary albumin and plasma XOR activity showed good correlation in topiroxostat group. The 50% inhibitory concentration (IC50 value) of febuxostat against plasma XOR in vitro was 12-fold higher than that of topiroxostat, and increased by approximately 13-fold by interfering with an exogenous protein. Topiroxostat caused reduced urinary albumin excretion, in which potent inhibition of the plasma XOR activity might be involved. PMID:27038523

  20. 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.

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

    Science.gov (United States)

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

    2016-06-01

    Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases. PMID:26567242

  2. Reduction of microalbuminuria by using losartan in normotensive patients with type 2 diabetes mellitus: A randomized controlled trial

    International Nuclear Information System (INIS)

    Type 2 diabetes mellitus (T2DM) is a worldwide pandemic that may lead to diabetic kidney disease (DKD), a complication which is the single most important and globally prevalent cause of chronic kidney disease. Microalbuminuria has been shown to be an early indicator of DKD and data suggest that angiotensin receptor blockers (ARBs) reduce urinary albumin excretion and retard the progression of renal disease in hypertensive T2DM patients. However, the effects of ARBs on preventing microalbuminuria and ensuing DKD in normotensive patients with T2DM is yet to be fully established. The objective of this study is to assess the anti-microalbuminuric effects of losartan therapy versus placebo in normotensive T2DM patients. This randomized single blinded controlled trial was performed at the Diabetic Clinic, Jinnah Hospital, Lahore over a period of 10 months. A total of 361 normotensive patients with T2DM and microalbuminuria were selected; of them, 171 patients were randomly allocated to the test group and 190 enrolled into the control group. The patients in the test group were started on losartan 50 mg/day for a six month period while those in the control group were put on vitamin B-12 500 mcg/day. The patients as well as the primary attending physicians/lab evaluators were blinded to the study. All study patients were followed up on a monthly basis. Quantitative microalbuminuria was tested at the beginning and at the end of the study. Out of the 171 patients in the test group, 149 (87.1%) had significant reduction of albuminuria by > 30% of their baseline (mean 101.9 +- 21.7 baseline and, 47.5 + - 12.9 post-therapy). The corresponding values for albuminuria in the 190 patients in the control group was mean 104.7 +- 26.3 baseline and post 6-month mean 103.9 +- 22.9, with P< 0.0001. The anti-albuminuric effect of losartan was reversible as seen on re-checking the urinary albumin two months after discontinuation of treatment. Our study shows that losartan was well tolerated

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

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

    2016-04-01

    This study proposed to validate a prediction model and risk-stratification tool of 2-year mortality rates of individuals in the general population suitable for office practice use. A risk indicator (R) derived from data in the literature was based on only 6 variables: to calculate R for an individual, starting with 0, for each year of age above 60, add 0.14; for a male, add 0.9; for diabetes mellitus, add 0.7; for albuminuria >30 mg/g of creatinine, add 0.7; for stage ≥3 chronic kidney disease (CKD), add 0.9; for cardiovascular disease (CVD), add 1.4; or for both CKD and CVD, add 1.7. We developed a univariate logistic regression model predicting 2-year individual mortality rates. The National Health and Nutrition Examination Survey (NHANES) data set (1999-2004 with deaths through 2006) was used as the target for validation. These 12,515 subjects had a mean age of 48.9±18.1 years, 48% males, 9.5% diabetes, 11.7% albuminuria, 6.8% CVD, 5.4% CKD, and 2.8% both CKD and CVD. Using the risk indicator R alone to predict mortality demonstrated good performance with area under the receiver operating characteristic (ROC) curve of 0.84. Dividing subjects into low-risk (R=0-1.0), low intermediate risk (R>1.0-3.0), high intermediate risk (R>3.0-5.0) or high-risk (R>5.0) categories predicted 2-year mortality rates of 0.52%, 1.44%, 5.19% and 15.24%, respectively, by the prediction model compared with actual mortality rates of 0.29%, 2.48%, 5.13% and 13.40%, respectively. We have validated a model of risk stratification using easily identified clinical characteristics to predict 2-year mortality rates of individuals in the general population. The model demonstrated performance adequate for its potential use for clinical practice and research decisions. PMID:26951378

  4. 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

  5. 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

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

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    Browne Gemma M

    2012-11-01

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

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Managing the asymptomatic diabetic patient with silent myocardial ischaemia.

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    Doubell, A F

    2002-01-01

    Coronary artery disease is common in diabetic patients and remains the major cause of death in these patients. However myocardial ischaemia resulting from coronary lesions does not always give rise to symptoms. The managing physician must therefore consider the benefit of screening for silent myocardial ischaemia in diabetic patients. Screening all diabetic patients is not recommended. The challenge to the physician is to select the patient subgroups likely to benefit from screening. Patients with more than one cardiac risk factor (dyslipidaemia, hypertension, smoking, family history, micro-albuminuria) in addition to diabetes, as well as patients with established macrovascular disease, e.g. peripheral vascular disease, will benefit most from screening. A standard treadmill stress ECG is the recommended screening test. A number of additional tests have been proposed to select high-risk patients for screening. Of these, testing for microalbuminuria and elevated CRP levels are most likely to influence decision-making. Once silent ischaemia has been detected in a diabetic patient, the mainstay of treatment remains the aggressive control of risk factors, improvement of glycaemic control and aspirin therapy. The use of beta-blockers and ACE-inhibitors often need consideration. The attending physician must then consider referring the patient to a cardiologist for angiography and possible intervention. This decision is based on the presence of poor prognostic signs during the stress ECG and the number of risk factors present. Microalbuminuria and elevated CRP levels are helpful in assisting with the risk stratification process. PMID:12389062

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

    International Nuclear Information System (INIS)

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

  13. Intravenous injection of ioxilan, iohexol and diatrizoate

    International Nuclear Information System (INIS)

    Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan. (orig.)

  14. ANTIHYPERGLYCEMIC ACTIVITY OF Exacum wightianum Arn. AN ENDEMIC MEDICINAL PLANT.

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    Madathupatti Ramanathan Udhayasankar

    2012-07-01

    Full Text Available An attempt was made to study the beneficial effects of ethanol extract of Exacum wightianum Arn. (Gentianaceae on its antihyperglycemic activity in streptozotocin induced diabetic rats. The pilot studies were carried after oral administration at doses of ethanolic extract of E. wightianum 100, 200, 500 and 1000 mg/kgb.wt. in sub-acute study. In diabetic induced rats fed with E. wightianum ethanol extract at 100 and 200 mg/kg body b.wt., the fasting plasma glucose levels were reduced to normal body and liver weight were found to be increased. Where as blood glucose, protein, albumin and creatinine levels were estimated after two weeks. Theextract significantly inhibited the induction of albuminuria, proteinemia and uremia. The present study clearly indicated a significant antidiabetic activity with the ethanol extract of E. wightianum supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Also the extract is useful in preventing the incidence of long term complications of diabetes mellitus.

  15. Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.

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    Laczy, Boglárka; Cseh, Judit; Mohás, Márton; Markó, Lajos; Tamaskó, Mónika; Koszegi, Tamás; Molnár, Gergo A; Wagner, Zoltán; Wagner, László; Wittmann, István

    2009-06-01

    Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients. PMID:18839054

  16. Renal function in diabetic nephropathy.

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    Dabla, Pradeep Kumar

    2010-05-15

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  17. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

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    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. PMID:25896609

  18. Murine membranous nephropathy: immunization with α3(IV) collagen fragment induces subepithelial immune complexes and FcγR-independent nephrotic syndrome.

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    Zhang, Jun-Jun; Malekpour, Mahdi; Luo, Wentian; Ge, Linna; Olaru, Florina; Wang, Xu-Ping; Bah, Maimouna; Sado, Yoshikazu; Heidet, Laurence; Kleinau, Sandra; Fogo, Agnes B; Borza, Dorin-Bogdan

    2012-04-01

    Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and a significant cause of end-stage renal disease, yet current therapies are nonspecific, toxic, and often ineffective. The development of novel targeted therapies requires a detailed understanding of the pathogenic mechanisms, but progress is hampered by the lack of a robust mouse model of disease. We report that DBA/1 mice as well as congenic FcγRIII(-/-) and FcRγ(-/-) mice immunized with a fragment of α3(IV) collagen developed massive albuminuria and nephrotic syndrome, because of subepithelial deposits of mouse IgG and C3 with corresponding basement membrane reaction and podocyte foot process effacement. The clinical presentation and histopathologic findings were characteristic of MN. Although immunized mice produced genuine anti-α3NC1 autoantibodies that bound to kidney and lung basement membranes, neither crescentic glomerulonephritis nor alveolitis ensued, likely because of the predominance of mouse IgG1 over IgG2a and IgG2b autoantibodies. The ablation of activating IgG Fc receptors did not ameliorate injury, implicating subepithelial deposition of immune complexes and consequent complement activation as a major effector pathway. We have thus established an active model of murine MN. This model, leveraged by the availability of genetically engineered mice and mouse-specific reagents, will be instrumental in studying the pathogenesis of MN and evaluating the efficacy of novel experimental therapies. PMID:22371398

  19. Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways.

    Science.gov (United States)

    Gomez, Ivan G; MacKenna, Deidre A; Johnson, Bryce G; Kaimal, Vivek; Roach, Allie M; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B Nelson; Duffield, Jeremy S

    2015-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti-miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti-miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β-induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  20. Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

    Science.gov (United States)

    Gomez, Ivan G.; MacKenna, Deidre A.; Johnson, Bryce G.; Kaimal, Vivek; Roach, Allie M.; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J.; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B. Nelson; Duffield, Jeremy S.

    2014-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti–miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti–miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β–induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  1. A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways.

    Science.gov (United States)

    Ka, Shuk-Man; Kuoping Chao, Louis; Lin, Jung-Chen; Chen, Shui-Tein; Li, Wen-Tai; Lin, Chien-Nan; Cheng, Jen-Che; Jheng, Huei-Ling; Chen, Ann; Hua, Kuo-Feng

    2016-02-01

    Uncontrolled inflammation is a leading cause of various chronic diseases. Cinnamaldehyde (CA) is a major bioactive compound isolated from the essential oil of the leaves of Cinnamomum osmophloeum kaneh that exhibits anti-inflammatory activity; however, the use of CA is limited by its cytotoxicity. Here, we synthesized three CA derivatives and identified 4-hydroxycinnamaldehyde-galactosamine (HCAG) as a low toxicity anti-inflammatory compound in vitro (HCAG IC50 ≫ 1600 µM; CA IC50=40 µM) and in vivo. HCAG reduced pro-inflammatory mediator expression in LPS-activated macrophages by inhibiting MAPK and PKC-α/δ phosphorylation, decreasing ROS generation and reducing NF-κB activation. HCAG also reduced NLRP3 inflammasome-derived IL-1β secretion by inhibiting the ATP-mediated phosphorylation of AKT and PKC-α/δ. In a mouse model of LPS-induced renal inflammation, we observed reduced albuminuria and a mild degree of glomerular proliferation, glomerular sclerosis and periglomerular inflammation in the HCAG-treated mice compared with the vehicle-treated mice. The underlying mechanisms for these renoprotective effects involved: (1) inhibited NLRP3 inflammasome activation; (2) decreased superoxide anion levels and apoptosis; and (3) suppressed activation of NF-κB and related downstream inflammatory mediators. PMID:26675345

  2. Treatment and Prevention of Common Complications of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sheikh Salahuddin Ahmed

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a worldwide public health problem with an increasing incidence and prevalence. Outcomes of CKD include not only complications of decreased kidney function and cardiovascular disease but also kidney failure causing increased morbidity and mortality. Unfortunately, CKD is often undetected and undertreated because of its insidious onset, variable progression, and length of time to overt kidney failure. Diabetes is now the leading cause of CKD requiring renal replacement therapy in many parts of the world, and its prevalence is increasing disproportionately in the developing countries. This review article outlines the current recommendations from various clinical guidelines and research studies for treatment, prevention and delaying the progression of both CKD and its common complications such as hypertension, anemia, renal osteodystrophy, electrolyte and acid-base imbalance, and hyperlipidemia. Recommendations for nutrition in CKD and measures adopted for early diabetic kidney disease to prevent further progression have also been reviewed. There is strong evidence that early detection and management of CKD can prevent or reduce disease progression, decrease complications and improve outcomes. Evidence supports that achieving optimal glucose control, blood pressure, reduction in albuminuria with a multifactorial intervention slows the progression of CKD. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria, a factor important for the progression of CKD.

  3. 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. PMID:26984204

  4. Sequential and functional renal scintiscanning in diabetic and hypertensive patients

    International Nuclear Information System (INIS)

    47 diabetics (94 kidneys), 30 diabetics with concurrent hypertension (60 kidneys), and 23 hypertensives (46 kidneys) were examined by renal serial functional scintiscanning with 131I-ortho-iodo-hippuric acid. For evaluation, camera nephrographs of the whole kidney, renal hemispheres, and renal cortex were used according to the technique of 'regions of interest', and the parameters of secretory value, maximum secretion, and elimination half-life were determined on this basis. With regard to the extent of hypertension, there are significant differences between all three groups for the elimination half-life; as far as the secretory value was concerned, there was a difference between the group with high hypertension and the two other groups. Significant differences in secretory value and elimination half-life were also observed in hypertensives with and without changes in the fundus of the eye. There was no noticeable difference between the three parameters in groups with and without albuminuria. (orig./AJ) 891 AJ/orig.- 892 MKO

  5. Spontaneous remission of membranous glomerulonephritis with successful fetal outcome: A case report and literature review.

    Science.gov (United States)

    Huang, Yan-Mei; Zhou, Hui-Rong; Zhang, Ling; Yang, Ke-Ke; Luo, Jiang-Xi; Zhao, Hai-Lu

    2016-06-01

    Membranous glomerulonephritis (MGN) represents an immunologically mediated disease characterized by deposition of immune complexes in the glomerular subepithelial space. Persistent proteinuria at diagnosis predicts poor prognosis. Pregnancy with MGN is a risk of fetal loss and may worsen maternal renal function.Here, we report a lady with MGN and proteinuria achieved spontaneous remission and successful fetal outcome naive to any medications. The 26-year old woman had 1-year history of persistent proteinuria (5.5-12.56 g/24 hours) and biopsy-proven MGN. Histopathological characteristics included glomerular basement membrane spikes, subepithelial monoclonal IgG immunofluorescence, and diffuse electron dense deposits. She was sticking to a regular morning exercise routine without any medications. After successful delivery of a full-term baby girl, the mother had improved proteinuria (0.56 g/24 hours) and albuminuria (351.96 g/24 hours contrasting 2281.6 g/24 hours before pregnancy). The baby had normal height and body weight at 4 months old.We identified more pregnancies with MGN in 5 case reports and 5 clinical series review articles (7-33 cases included). Spontaneous remission of maternal MGN with good fetal outcome rarely occurred in mothers on immunosuppressive therapy.Mothers naive to immunosuppressive therapy may achieve spontaneous remission of maternal membranous glomerulonephritis and successful fetal outcome. Theoretically, fetus might donate stem cells to heal mother's kidney. PMID:27368022

  6. Hypertension in Chronic Glomerulonephritis.

    Science.gov (United States)

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Liu, Chungang; Song, Jingjing; Teng, Meiyu; Zheng, Xiaoyi; Li, Xiangmei; Tian, Yue; Pan, Minlian; Li, Yuhuan; Lee, Robert J; Wang, Di

    2016-01-01

    Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet-streptozotocin- (STZ-) induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-β-d-glucosaminidase verified CM's renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3β in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats. PMID:27274781

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

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    Chungang Liu

    2016-01-01

    Full Text Available Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM in diet-streptozotocin- (STZ- induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-β-d-glucosaminidase verified CM’s renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3β in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats.

  11. Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients.

    Science.gov (United States)

    Fiseha, Temesgen

    2015-01-01

    Diabetic nephropathy (DN) is a serious complication of diabetes associated with increased risk of mortality, and cardiovascular and renal outcomes. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney function and improve patient outcomes. Urinary biomarkers may be elevated in diabetic patients even before the appearance of microalbuminuria, and can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early DN). We reviewed some new and important urinary biomarkers, such as: Neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase (NAG), Cystatin C, alpha 1-microglobulin, immunoglobulin G or M, type IV collagen, nephrin, angiotensinogen and liver-type fatty acid-binding protein (L-FABP) associated with early DN in type 2 diabetic patients. Our search identified a total of 42 studies that have been published to date. Urinary levels of these biomarkers were elevated in type 2 diabetic patients compared with non-diabetic controls, including in patients who had no signs indicating nephropathy (without microalbuminuria), and showed positive correlation with albuminuria. Despite the promise of these new urinary biomarkers, further large, multicenter prospective studies are still needed to confirm their clinical utility as a screening tool for early type 2 DN in every day practice. PMID:26146561

  12. 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.

  13. Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress.

    Science.gov (United States)

    Zheng, Jing; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; McCarty, Mark F; Fujii, Masakazu; Ikeda, Noriko; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-01-15

    We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy. PMID:23115122

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

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    Vladu Mihaela

    2014-09-01

    Full Text Available Background and Aims: Diabetes mellitus (DM is a chronic disease which can evolve towards devastating micro and macro-vascular complications. Chronic kidney disease (CKD is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD and premature death. The aim of our study was to evaluate the prognosis in patients with DM and CKD, depending on estimated glomerular filtration rate (eGFR and albuminuria, according to the classification of Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (KDIGO from 2013 Materials and Methods: The study was epidemiological, transversal, non interventional type, with 600 subjects unselected patients divided into three subgroups: 200 patients with T1DM, 200 patients with T2DM and 200 age matched subjects without DM. The recorded data have been analyzed using the Statistic Package for Social Sciences (SPSS, the 17.00 software (IBM Corporation, Armonk, NY, United States of America. Results:. We found a statistically significant difference among the three study groups (p < 0.0001 regarding the prognosis of CKD. Conclusions: DM represents an important risk factor for the appearance of CKD but also a negative prognosis factor for the patients with CKD.

  15. YKL-40 - an emerging biomarker in cardiovascular disease and diabetes

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    Rathcke Camilla

    2009-01-01

    Full Text Available Abstract Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis. Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial dysfunction, atherosclerosis, cardiovascular disease and diabetes and look ahead on future perspectives of YKL-40 research.

  16. Risks of rapid decline renal function in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Yi-Jing; Sheen; Wayne; HH; Sheu

    2014-01-01

    Progressive rising population of diabetes and related nephropathy, namely, diabetic kidney disease and associated end stage renal disease has become a major global public health issue. Results of observational studies indicate that most diabetic kidney disease progresses over decades; however, certain diabetes patients display a rapid decline in renal function, which may lead to renal failure within months. Although the definition of rapid renal function decline remained speculative, in general,it is defined by the decrease of estimated glomerular filtration rate(e GFR) in absolute rate of loss or percent change. Based on the Kidney Disease: Improving Global Outcomes 2012 clinical practice guidelines, a rapid decline in renal function is defined as a sustained declinein e GFR of > 5 m L/min per 1.73 m2 per year. It has been reported that potential factors contributing to a rapid decline in renal function include ethnic/genetic and demographic causes, smoking habits, increased glycated hemoglobin levels, obesity, albuminuria, anemia, low serum magnesium levels, high serum phosphate levels, vitamin D deficiency, elevated systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity values, retinopathy, and cardiac autonomic neuropathy. This article reviews current literatures in this area and provides insight on the early detection of diabetic subjects who are at risk of a rapid decline in renal function in order to develop a more aggressive approach to renal and cardiovascular protection.

  17. Experimental gentamicin-induced nephrotoxicity in the sheep

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    Fartashvand Majid

    2014-12-01

    Full Text Available The aim of the study was to investigate the nephrotoxic effects of gentamicin in adult male sheep, and to identify the earliest signs of toxicity and the extent of clinical and biochemical changes. Twenty clinically healthy yearling male Iranian fattailed sheep were injected with gentamicin sulfate at a daily dose of 80 mg/kg for 9-10 d when nephrotoxicosis was induced. Blood samples were collected weekly before and after induction of nephrotoxicosis. Gentamicin-induced nephrotoxicity was characterised by increased creatinine and urea levels in serum, electrolyte imbalances, occurrence of albuminuria, and renal dysfunction. Significant elevation in respiratory and heart rates were observed one week after treatment (P < 0.05. There was a noticeable increase in water consumption, lethargy, and loss of appetite in treated sheep. There were significant correlations between serum creatinine and potassium (P = 0.004, r = 0.759, sodium (P = 0.017, r = 0.501, and urea (P = 0.021, r = 0.617 levels. Additionally, significant negative correlations between serum total protein and albumin and creatinine (P = 0.023, r = -0.484 and urea (P = 0.036, r = -0.381 were found. At necropsy, the kidneys were pale, swollen, and wet on the cut surface, especially perirenal tissues and ureters were oedematous. These findings confirmed the previous reports in other species.

  18. Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes

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    Thomas Bernd Dschietzig

    2015-03-01

    Full Text Available Background/Aims: In diabetic nephropathy (DN, the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC, there is no specific remedy available. Relaxin-2 (Rlx - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 µg/kg/day and high-dose (320 µg/kg/day Rlx were tested against vehicle (n = 20 each and non-diabetic controls (n = 14 for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-β pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-β-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.

  19. Growth arrest specific protein 6 participates in DOCA-induced target-organ damage.

    Science.gov (United States)

    Park, Joon-Keun; Theuer, Stefanie; Kirsch, Torsten; Lindschau, Carsten; Klinge, Uwe; Heuser, Arnd; Plehm, Ralph; Todiras, Mihai; Carmeliet, Peter; Haller, Hermann; Luft, Friedrich C; Muller, Dominik N; Fiebeler, Anette

    2009-08-01

    Growth arrest-specific protein 6 (Gas 6) is involved in inflammatory kidney diseases, vascular remodeling, cell adhesion, and thrombus formation. We explored a role for Gas 6 in aldosterone-induced target organ damage. We observed that Gas 6 was upregulated in rats with high aldosterone levels. Mineralocorticoid receptor blockade prevented target organ damage and decreased the elevated Gas 6 expression. Vascular smooth muscle cells given aldosterone increased their Gas 6 expression in vitro. To test the pathophysiological relevance, we investigated the effects of deoxycorticosterone acetate (DOCA) on Gas 6 gene-deleted ((-/-)) mice. After 6 weeks DOCA, Gas 6(-/-) mice developed similar telemetric blood pressure elevations compared to wild-type mice but were protected from cardiac hypertrophy. Cardiac expression of interleukin 6 and collagen IV was blunted in Gas 6(-/-) mice, indicating reduced inflammation and fibrosis. Gas 6(-/-) mice also had an improved renal function with reduced albuminuria, compared to wild-type mice. Renal fibrosis and fibronectin deposition in the kidney were also reduced. Gas 6 deficiency reduces the detrimental effects of aldosterone on cardiac and renal remodeling independent of blood pressure reduction. Gas 6 appears to play a role in mineralocorticoid receptor-mediated target organ damage. Furthermore, because warfarin interferes with Gas 6 protein expression, the findings could be of clinical relevance for anticoagulant choices. PMID:19564549

  20. 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.

  1. Association between serum cystatin C levels and cardiovascular disease in type 2 diabetic patients.

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    Triki, Sonia; Fekih, Ons; Hellara, Ilhem; Neffati, Fadoua; Douki, Wahiba; Hamda, Khaldoun Ben; Maatouk, Faouzi; Najjar, Mohamed Fadhel

    2013-01-01

    Serum cystatin C concentration was recently reported as a marker of cardiovascular disease (CVD). In the present study, we evaluated the association between the increase of serum cystatin C levels and the risk of CVD in type 2 diabetes. 42 patients with type 2 diabetes were included in the present study; 27 of them have CVD. The control group consisted of 30 healthy adults. Cystatin C, creatinine, microalbuminuria and CRP were measured on Cobas 6000(TM). Cystatine C level was significantly higher in patients with CVD. A significant difference in serum cystatin C was found in patients with and without CVD among albuminuria. No difference in serum cystatin C levels was found according to number of affected vessels. A cystatin C level above 1.10 mg/L was associated with increase of risk of CVD with significant difference (OR = 42.52; IC 95% 1.455 to 1242.827 and p = 0.029). Our results suggested that the increase of serum cystatin C concentrations is a potential marker for CVD in diabetes. PMID:23906571

  2. [Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?].

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    Dhia, Rym Ben; Hellara, Ilhem; Harzallah, Olfa; Neffati, Fadoua; Khochtali, Ines; Mahjoub, Sylvia; Najjar, Mohamed Fadhel

    2012-01-01

    Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients. PMID:22565176

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

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    Simon J Freeley

    Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

  4. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

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    Gluhovschi, Gheorghe; Petrica, Ligia; Timar, Romulus; Velciov, Silvia; Ionita, Ioana; Kaycsa, Adriana; Timar, Bogdan

    2016-01-01

    Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

  5. Epidemiology investigation and associated factors analysis of chronic kidney disease among adults older than 35 years in Tianshan district of Urumqi, Xinjiang%乌鲁木齐市天山区35岁以上成人慢性肾脏病流行病学调查及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    赵红娟; 徐钢; 刘晓城; 陆晨; 岳华; 姬佳妮; 马慧霞; 范淑英; 沙力汗.沙塔尔; 刘伟莉; 朱开春

    2010-01-01

    Objective To investigate the prevalence of chronic kidney disease (CKD)and risk factors in the adult population of Tianshan district in Urumqi, Xinjiang. Methods A total of 2131 residents from 4 communities in Tianshan district of Urumqi city were randomly selected using a stratified, multistage sampling. All the residents were interviewed and tested for morning spot urine of albumin to creatinine ratio (ACR) (abnormal ≥ 30 mg/g), morning spot urine dipstick of hematuria ( abnormal >3 red blood cells/HP or greater) and pyuria ( abnormal> 5 white blood cells/HP) confirmed by microscopy. Renal function was determined with abbreviated MDRD equation [reduced estimated glomerular filtration rate (eGFR)<60 ml ·min-1 ·(1.73 m2)-1]. The associations of kidney damage indicators with age, gender, hypertension, diabetes mellitus, income,education, cholesterol, triglyceride and smoking were examined. Results Eligible data of 2131 subjects were collected in the study. After the adjustment of age and gender component, the prevalence of albuminuria was found in 2.63% (95%CI:1.78%-3.48%) of subjects, hematuria in 7.43%(95%CI:6.11%-8.75%) and reduced renal function in 1.72%(95%CI:1.08%-2.35%).Approximately 9.99%(95%CI:8.47%-11.55%) of subjects had at least one indicator of kidney damage. Multivariate logistic regression revealed that albuminuria, hematuria, age and hyperuricemia were independently associated with reduced renal function. Hematuria and reduced renal function were independently associated with albuminuria. Albuminuria, reduced renal function and female were independently associated with hematuria. Conclusion In urban adult population over 35 years old of Urumqi, a big city in western China, the prevalence of CKD is 9.99%, the recognition is 2.44% and the risk factors of CKD are similar to those of other domestic big cities and western developed countries.%目的 了解乌鲁木齐市天山区35岁以上成人慢性肾脏

  6. The total urine protein-to-creatinine ratio can predict the presence of microalbuminuria.

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    Kyoko Yamamoto

    Full Text Available The Kidney Disease: Improving Global Outcomes chronic kidney disease (CKD guidelines recommend that CKD be classified based on the etiology, glomerular filtration rate (GFR and degree of albuminuria. The present study aimed to establish a method that predicts the presence of microalbuminuria by measuring the total urine protein-to-creatinine ratio (TPCR in patients with cardiovascular disease (CVD risk factors.We obtained urine samples from 1,033 patients who visited the cardiovascular clinic at St. Luke's International Hospital from February 2012 to August 2012. We measured the TPCR and the urine albumin-to-creatinine ratio (ACR from random spot urine samples. We performed correlation, receiver operating characteristic (ROC curve, sensitivity, and subgroup analyses. There was a strong positive correlation between the TPCR and ACR (R2 = 0.861, p<0.001. A ROC curve analysis for the TPCR revealed a sensitivity of 94.4%, a specificity of 86.1%, and an area under the curve of 0.903 for detecting microalbuminuria for a TPCR cut-off value of 84 mg/g of creatinine. The subgroup analysis indicated that the cut-off value could be used for patients with CVD risk factors.These results suggest that the TPCR with an appropriate cut-off value could be used to screen for the presence of microalbuminuria in patients with CVD risk factors. This simple, inexpensive measurement has broader applications, leading to earlier intervention and public benefit.

  7. Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

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    Takahashi, S; Katada, J; Daida, H; Kitamura, F; Yokoyama, K

    2016-09-01

    Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia. PMID:26674759

  8. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease.

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    Paola Krall

    Full Text Available Mutations in the TRPC6 calcium channel (Transient receptor potential channel 6 gene have been associated with familiar forms of Focal and Segmental Glomerulosclerosis (FSGS affecting children and adults. In addition, acquired glomerular diseases are associated with increased expression levels of TRPC6. However, the exact role of TRPC6 in the pathogenesis of FSGS remains to be elucidated. In this work we describe the generation and phenotypic characterization of three different transgenic mouse lines with podocyte-specific overexpression of the wild type or any of two mutant forms of Trpc6 (P111Q and E896K previously related to FSGS. Consistent with the human phenotype a non-nephrotic range of albuminuria was detectable in almost all transgenic lines. The histological analysis demonstrated that the transgenic mice developed a kidney disease similar to human FSGS. Differences of 2-3 folds in the presence of glomerular lesions were found between the non transgenic and transgenic mice expressing Trpc6 in its wild type or mutant forms specifically in podocytes. Electron microscopy of glomerulus from transgenic mice showed extensive podocyte foot process effacement. We conclude that overexpression of Trpc6 (wild type or mutated in podocytes is sufficient to cause a kidney disease consistent with FSGS. Our results contribute to reinforce the central role of podocytes in the etiology of FSGS. These mice constitute an important new model in which to study future therapies and outcomes of this complex disease.

  9. Evaluation of microalbuminuria in obese children and its relation to metabolic syndrome.

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    Sanad, Mohammed; Gharib, Amal

    2011-12-01

    Several epidemiologic studies have clearly demonstrated that obesity increases the risk of kidney diseases. We have attempted to evaluate the association of obesity with albuminuria, an early marker of kidney disease, among obese children and its relation to metabolic syndrome. This study included 150 obese children. Blood pressure, fasting blood glucose, plasma insulin and the lipid profile were assessed. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate in vivo insulin resistance. Urinary albumin and creatinine were estimated. Microalbuminuria was detected in 22 (14.7%) of the obese children. Waist circumference, blood pressure, triglyceride, low-density lipoprotein (LDL), insulin resistance and fasting blood glucose were significantly higher in obese children with microalbuminuria than in those with normoalbuminuria and showed significant positive correlations with microalbuminuria. High-density lipoprotein (HDL) was significantly lower in obese children with microalbuminuria than in those with normoalbuminuria, with a significant negative correlation with microalbuminuria. We found that body mass index, abdominal obesity, hypertension, impaired fasting glucose level and insulin resistance significantly increased the odds of microalbuminuria in the obese children enrolled in this study. Moreover, high triglyceride, high LDL and low HDL were significantly associated with microalbuminuria. In our patient group, childhood obesity was a risk factor for the development of microalbuminuria, which in turn was significantly associated with metabolic syndrome and its different constituents. PMID:21638155

  10. The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications.

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    Avogaro, Angelo; Fadini, Gian Paolo

    2014-10-01

    We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: ("diabetes" OR "diabetic") AND ("retinopathy" OR "retinal" OR "nephropathy" OR "renal" OR "albuminuria" OR "microalbuminuria" OR "neuropathy" OR "ulcer" OR "wound" OR "bone marrow"); ("dipeptidyl peptidase-4" OR "dipeptidyl peptidase-IV" OR "DPP-4" OR "DPP-IV"); and ("inhibition" OR "inhibitor"). Experimentally, DPP4-I appears to improve inflammation, endothelial function, blood pressure, lipid metabolism, and bone marrow function. Several experimental studies report direct potential beneficial effects of DPP4-I on all microvascular diabetes-related complications. These drugs have the ability to act either directly or indirectly via improved glucose control, GLP-1 bioavailability, and modifying nonincretin substrates. Although preliminary clinical data support that DPP4-I therapy can protect from microangiopathy, insufficient evidence is available to conclude that this class of drugs directly prevents or decreases microangiopathy in humans independently from improved glucose control. Experimental findings and preliminary clinical data suggest that DPP4-I, in addition to improving metabolic control, have the potential to interfere with the onset and progression of diabetic microangiopathy. Further evidence is needed to confirm these effects in patients with diabetes. PMID:25249673

  11. Interaction of the renin angiotensin and cox systems in the kidney.

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    Quadri, Syed S; Culver, Silas A; Li, Caixia; Siragy, Helmy M

    2016-01-01

    Cyclooxygenase-2 (COX-2) plays an important role in mediating actions of the renin-angiotensin system (RAS). This review sheds light on the recent developments regarding the complex interactions between components of RAS and COX-2; and their implications on renal function and disease. COX-2 is believed to counter regulate the effects of RAS activation and therefore counter balance the vasoconstriction effect of Ang II. In kidney, under normal conditions, these systems are essential for maintaining a balance between vasodilation and vasoconstriction. However, recent studies suggested a pivotal role for this interplay in pathology. COX-2 increases the renin release and Ang II formation leading to increase in blood pressure. COX-2 is also associated with diabetic nephropathy, where its upregulation in the kidney contributes to glomerular injury and albuminuria. Selective inhibition of COX-2 retards the progression of renal injury. COX-2 also mediates the pathologic effects of the (Pro)renin receptor (PRR) in the kidney. In summary, this review discusses the interaction between the RAS and COX-2 in health and disease. PMID:27100703

  12. MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy.

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    Qiao, Yingjin; Berg, Anna-Lena; Wang, Pei; Ge, Yan; Quan, Songxia; Zhou, Sijie; Wang, Hai; Liu, Zhangsuo; Gong, Rujun

    2016-01-01

    Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms. PMID:27270328

  13. Continuous versus intermittent exercise effects on urinary excretion of albumin and total protein.

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    Montelpare, W J; Klentrou, P; Thoden, J

    2002-09-01

    Several studies have reported post-exercise increases of urinary concentrations of plasma proteins. However, under normal conditions, through mechanisms of size and electrical charge selection, the kidney restricts the clearance of molecules as large as albumin. Post-exercise increases in albuminuria occur following the physiological stress of intense exercise, most likely as a result of the exercise induced blood acidity changes which lead to a change in the arrangement of the albumin molecule, and subsequently the filtration characteristics of the glomerular capillary wall. The purpose of the present study was therefore to determine the extent to which different types of exercise could induce a transient condition of post-exercise increases in the urinary output of total protein and albumin. All 14 males, who agreed to participate in the study, performed a continuous and an intermittent cycling protocol on a stationary bicycle ergometer. The results showed that: a) intermittent exercise had a greater influence than continuous exercise on the total output of urine albumin, and of urine total protein; b) concentrations of blood pH and blood lactate, were associated with changes in the clearance of urine albumin and urine total protein. Post-exercise proteinuria response seems to be transient and therefore renal trauma is not suspected at the early stages of observation. Furthermore, these results indicate that the kidney undergoes distinct physiological adjustments during exercise, and that these adjustments are relative to the intensity of the exercise stress. PMID:12413038

  14. Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase.

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    Peng, Chiung-Huei; Yang, Yi-Sun; Chan, Kuei-Chuan; Wang, Chau-Jong; Chen, Mu-Lin; Huang, Chien-Ning

    2014-10-01

    The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy. PMID:25226384

  15. Metabolic syndrome and incident coronary heart disease in Australian indigenous populations.

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    Li, Ming; McCulloch, Brad; McDermott, Robyn

    2012-06-01

    This report aims to compare the prediction of the metabolic syndrome (MetS) and its components for morbidity and mortality of coronary heart disease (CHD) in a cohort of Australian Aboriginal and Torres Strait Islander adults (TSIs). A total of 2,100 adults (1,283 Aborigines and 817 TSIs) was followed up for 6 years from 2000. Outcome measures were all CHD events (deaths and hospitalizations). Baseline anthropometric measurements, blood pressure (BP), fasting blood lipids and glucose were collected. Smoking and alcohol intake was self-reported. We found MetS was more prevalent in TSI (50.3%) compared to Aborigines (33.0%). Baseline MetS doubled the risk of a CHD event in Aborigines. Increased fasting triglycerides was stronger in predicting CHD (hazard ratio (HR): 2.8) compared with MetS after adjusted for age, sex, tobacco and alcohol consumption, and baseline diabetes and albuminuria for Aborigines but not among TSIs. MetS was not more powerful than its components in predicting CHD event. In Australian Aborigines, the "triglyceridemic waist" phenotype strongly predicts CHD event, whereas among TSI, baseline diabetes mediated the prediction of increased fasting glucose for CHD event. PMID:21660075

  16. Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006

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    Sturniolo Antonio

    2010-06-01

    Full Text Available Abstract Background Environmental factors have been associated with the outbreak of chronic kidney disease (CKD. We evaluated the association of Cadmium (Cd exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES. Methods 5426 subjects ≥ 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB after adjustment for age, gender, race/ethnicity, body mass index and smoking habits. Results Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001. Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046 and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007. An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014. Conclusions Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population.

  17. Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

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    Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

    2014-01-01

    VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

  18. 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.

  19. P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or to N-acetylcysteine supplementation [corrected].

    Science.gov (United States)

    Rodrigues, Adelson M; Bergamaschi, Cassia T; Fernandes, Maria Jose S; Paredes-Gamero, Edgar J; Buri, Marcus V; Curi, Marcus V; Ferreira, Alice T; Araujo, Sergio R R; Punaro, Giovana R; Maciel, Fabiane R; Nogueira, Guilherme B; Higa, Elisa M S

    2014-01-01

    Previous studies in our laboratory showed that N-acetylcysteine supplementation or aerobic training reduced oxidative stress and the progression of diabetic nephropathy in rats. The P2X(7 receptor is up-regulated in pathological conditions, such as diabetes mellitus. This up-regulation is related to oxidative stress and induces tissue apoptosis or necrosis. The aim of the present study is to assess the role of P2X(7) receptor in the kidneys of diabetic rats submitted to aerobic training or N-acetylcysteine supplementation. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg, i.v.) and the training was done on a treadmill; N-acetylcysteine was given in the drinking water (600 mg/L). By confocal microscopy, as compared to control, the kidneys of diabetic rats showed increased P2 × 7 receptor expression and a higher activation in response to 2'(3')-O-(4-benzoylbenzoyl) adenosine5'-triphosphate (specific agonist) and adenosine triphosphate (nonspecific agonist) (all prats treated with N-acetylcysteine, exercise or both. We also observed measured proteinuria and albuminuria (early marker of diabetic nephropathy) in DM groups. Lipoperoxidation was strongly correlated with P2X(7) receptor expression, which was also correlated to NO•, thus associating this receptor to oxidative stress and kidney lesion. We suggest that P2X(7) receptor inhibition associated with the maintenance of redox homeostasis could be useful as coadjuvant treatment to delay the progression of diabetic nephropathy. PMID:24940871

  20. 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.

  1. [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). PMID:7148252

  2. JAK inhibition in the treatment of diabetic kidney disease.

    Science.gov (United States)

    Brosius, Frank C; Tuttle, Katherine R; Kretzler, Matthias

    2016-08-01

    Diabetic kidney disease (DKD) is the most common cause of kidney failure in many countries today, but treatments have not improved in the last 20 years. Recently, systems biology methods have allowed the elucidation of signalling pathways and networks involved in the progression of DKD that were not well appreciated previously. A prominent pathway found to be integrally associated with DKD progression is the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Increased expression of JAK-STAT genes was found in multiple cells in the kidney, including glomerular podocytes, in both early and progressive DKD. Subsequent experiments in a mouse diabetic model showed that enhanced expression of JAK2 selectively in glomerular podocytes increased functional and pathological features of DKD. Finally, a yet unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled study of the efficacy of a selective JAK1 and JAK2 inhibitor has been conducted in type 2 diabetic participants with DKD. In this trial there was a reduction of albuminuria in participants who received the active inhibitor compared with those who received a placebo These results support the further study of JAK inhibitors as a new therapy for DKD. This review summarises a presentation given at the 'Anti-inflammatory interventions in diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by an overview by the Session Chair, Hiddo Heerspink (DOI: 10.1007/s00125-016-4030-4 ). PMID:27333885

  3. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.

    Science.gov (United States)

    Inzucchi, Silvio E; Zinman, Bernard; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Hantel, Stefan; Espadero, Rosa-Maria; Woerle, Hans-Jürgen; Broedl, Uli C; Johansen, Odd Erik

    2015-03-01

    Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia. In this review, we outline those CV risk factors that this class appears to influence and provide the design features and trial characteristics of six ongoing outcome trials involving more than 41,000 individuals with T2DM. Those risk factors beyond glucose that can potentially be modulated positively with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity, hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels and oxidative stress. On the other hand, small increases in low-density lipoprotein (LDL)-cholesterol levels have also been observed for the class, which theoretically might offset some of these benefits. The potential translational impact of these effects is being tested with outcome trials, also reviewed in this article, powered to assess both macrovascular as well as certain microvascular outcomes in T2DM. These are expected to begin to report in late 2015. PMID:25589482

  4. [Management of uncomplicated arterial hypertension in pregnancy].

    Science.gov (United States)

    Gullotti, D; Gullotti, A; Schillaci, L; Lo Genco, A; Figlioli, F; Pira, M; Rotolo, G

    2006-02-01

    In the management of uncomplicated arterial hypertension in pregnancy, blood pressure (BP) values of pregnant women should be treated in order to reduce risks of both maternal and fetal complications. To reduce these risks, it is necessary to monitor BP, some hematochemical parameters and albuminuria, to try to prevent more serious clinical complications. Moreover, repeated measurements of BP, as well as frequent ambulatory blood pressure monitoring (ABPM) over 24 h are necessary. In the treatment of hypertension in pregnancy, if there are no high risks, it is possible to try a non pharmacological antihypertensive therapy consisting of a suitable diet, reduction of weight, abolition of some lifestyles (smoking, excessive alcohol consumption and heavy physical exercises). If these measures are not sufficient or the risk is high, a pharmacological therapy with neither toxic nor teratogenic drugs for the fetus will be administered in order to normalize BP without reducing perfusion of the uterus/placenta. Only in case of severe hypertension, a more aggressive pharmacological treatment should be carried out and, if necessary, hospitalization. The drugs suggested in these cases are those which have already been recognised as presenting low side effects. Antihypertensive drugs used in pregnancy can be classified as: suitable (methyldopa, clonidine, long acting calcioantagonists); cautiously used (alpha-blockers, beta-betablockers); contraindicated (ACE-inhibitors, sartans, short acting calcioantagonists). Hyper-tensive crises should be treated with an injection therapy (clonidine, labetalol), with hospital admission if necessary, or if preeclampsia or eclampsia may occur. PMID:16565702

  5. Perindopril/indapamide combination in the first-line treatment of hypertension and end-organ protection.

    Science.gov (United States)

    Gosse, Philippe

    2006-05-01

    This article examines evidence-based findings in the literature on the efficacy of perindopril 2 mg/indapamide 0.625 mg, a first-line, low-dose antihypertensive drug combination. In regulatory Phase II and III trials, perindopril/indapamide significantly lowered blood pressure compared with other first-line therapies (atenolol, losartan and irbesartan). This was also the case in STRAtegies of Treatment in Hypertension: Evaluation, a postregistration study versus current monotherapies and stepped-care therapy with different classes of antihypertensive agents. The efficacy/safety ratio (both clinical and with regard to laboratory parameters) of perindopril/indapamide was good. Perindopril/indapamide provides additional antihypertensive efficacy compared with each component used alone and with current monotherapies, with major efficacy on systolic blood pressure, an important predictor of cardiovascular risk. It also reduces pulse pressure, an independent cardiovascular risk factor, large-vessel arterial stiffness and microcirculatory alterations. The fixed dosage of a once-daily tablet, ensures optimal ease of use and enhances patient compliance. Perindopril/indapamide also reduces target organ damage in patients at high cardiovascular risk, such as patients with cardiac hypertrophy and Type 2 diabetics with albuminuria. These benefits, together with the good efficacy/tolerability ratio, fulfill the requirements of the European Society of Hypertension and of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines for low-dose, first-line combination therapy in hypertension. PMID:16716093

  6. Biomarkers of Renal Disease and Progression in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Radovan Hojs

    2015-05-01

    Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

  7. Clinical significance of determination of GFR, urinary albumin and UAlb/UCr in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Objective: To study the diagnostic value of determination of glomerular filtration rate (GFR), Urinary albumin (UAlb) and UAlb/UCr for early diabetic nephropathy in patients with type 2 Diabetes. Methods: UAlb, UAlb/UCr were measured with radioimmunoassay (RIA) and GFR measured with Tcm DTPA dynamic renal imaging in 102 DM2 patients with diabetic nephropathy (DN) and 23 DM2 patients without nephropathy. Results: In diabetics with nephropathy with a disease course of less than five years (n=38), the GFR, UAlb/UCr were significantly higher than those in diabetics without nephropathy. With prolongation of the disease, GFR gradually declined and UAlb/UCr rose further and in patients with nephropathy with disease courses over 10 years, the GFR was significantly lower and UAlb/UCr significantly higher than those in diabetics without nephropathy (all P<0.05). The GFR was negatively correlated with course of disease, BMI and UAlb/UCr (r=-0.691, -0.631, -0.698, respectively, P<0.01). Conclusion: GFR can reflect the degree of renal damage of diabetic patients,and may be helpful for evaluation of progression of DN when combined with assay of albuminuria. (authors)

  8. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease. PMID:27029428

  9. LONG-TERM THERAPY WITH INDAPAMIDE IN ELDERLY AND SENILE PATIENTS WITH HYPERTENSION: CARDIORENOPROTECTIVE EFFECTS AND INFLUENCE ON QUALITY OF LIFE

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Aim. To estimate cardiorenoprotective effect of 12-month therapy by indapamide in elderly and senile patients with arterial hypertension (HT and its influence on quality of life.Material and methods. 40 elderly and senile patients with HT were examined. 70% of patients received monotherapy by indapamide 2,5 mg once daily and 30% of patients were treated with indapamide and lisinopril combination. Duration of observation was 12 months. Ambulatory blood pressure (BP monitoring, echocardiography, plasma lipid profile, glycemia and uricemia levels and potassium serum level was evaluated initially and after 12 months of therapy. Glomerular filtration rate and albuminuria as well as patient quality of life also was evaluated.Results. Target BP level was reached in all patients during 12 month therapy. Reduction of average 24-hour, day and night BP, BP load, rate of morning BP rising was observed. Negative influence on BP variability was not found. Improvement of daily BP profile also was found. The indapamide reduced left ventricle mass, improved renal function, vessel resistance and quality of life. Negative influence of long-term therapy with indapamide on lipid, glucose, purine metabolism and serum potassium level was not observed.Conclusion. Indapamide is an effective antihypertensive drug for long-term treatment of elderly and senile patients with HT of 1-2 degree.

  10. Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats.

    Science.gov (United States)

    Ma, Song-Tao; Liu, Dong-lian; Deng, Jing-jing; Niu, Rui; Liu, Rui-bin

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. PMID:23147865

  11. Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease.

    Science.gov (United States)

    Piccoli, Giorgina B; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M; Pani, Antonello; Veltri, Andrea

    2015-01-01

    The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID:26676663

  12. The early modern kidney--nephrology in and about the nineteenth century. Part 1.

    Science.gov (United States)

    Eknoyan, Garabed

    2013-01-01

    The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789-1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816-1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816-1895) and for active tubular transport by Rudolf Heidenhain (1834-1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis). PMID:23278189

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We...... 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.......2 [8.1-123.4], P < 0.05 for all comparisons). U-LFABP correlates with the urinary albumin-to-creatinine ratio (R(2) = 0.54, P < 0.001). In the intervention study, all doses of lisinopril significantly reduced urinary albumin excretion rate and U-LFABP from baseline. The reductions in U-LFABP were 43...

  14. 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.; Stehouwer, C.D.; Schalkwijk, C.G.; Tarnow, L.; Parving, Hans-Henrik

    2008-01-01

    molecule-1 (sICAM-1), sE-selectin, transforming growth factor-beta (TGF-beta) and AGE peptides. Mean standard deviation scores (Z-scores) were used to combine biomarker information. RESULTS: In a Cox enter model with combined Z-scores for biomarkers of endothelial dysfunction (vWf, sVCAM-1, sICAM-1, sE-selectin......) and for biomarkers of inflammation (hs-CRP, IL-6, fibrinogen), endothelial dysfunction (hazard ratio for a 28 % increase ( = 1 SD) in Z-score) 3.20 (1.56 to 6.56), p = 0.001) and UAER (HR for a 75 % increase ( = 1 SD) in UAER) 2.61 (1.30 to 5.23), p = 0.007) were found as independent predictors....... Independently, IL-6 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...

  15. Sequential RAAS blockade: is it worth the risk?

    Science.gov (United States)

    Persson, Frederik; Rossing, Peter

    2014-03-01

    Soon after the emergence of the renin-angiotensin-aldosterone system (RAAS) blocking treatment as the cornerstone of renoprotective treatment in the prevention and treatment of diabetic and nondiabetic CKD, it was investigated if a higher degree of achievable RAAS blockade by combining more than one compound is feasible and advantageous. Regardless of the benefits from using monotherapy for diabetic kidney disease, there is still much improvement to wish for in terms of kidney prognosis in these populations. A great deal of research has gone into evaluating combinations of the RAAS blocking treatments in different populations and with different drugs and doses. Studies have mostly been short-term and use surrogate endpoints such as albuminuria. Side effects have been well known and expected in terms of increasing potassium levels and hypotension, but to an acceptable extent. With recent disappointing results from major hard endpoint trials using dual RAAS blockade the concept is now under scrutiny. In this review we will discuss the pros and cons of dual RAAS blockade, with facts and findings from smaller studies, endpoint trials, and meta-analyses. PMID:24602465

  16. Relationship of endothelial dysfunction with degree of renal function damage and lipidemic profile in patients with type 2 diabetes mellitus and hypertension

    Directory of Open Access Journals (Sweden)

    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.

  17. [Headache caused by pesticides--a review of the literature].

    Science.gov (United States)

    Titlić, Marina; Josipović-Jelić, Zeljka; Punda, Ante

    2008-05-01

    Headache makes one of the most common side effects of frequently pesticide application. This is to be taken care of in rural areas. Headaches have been reported with the use of ivermectin, ivermectin-diethylcarbamazine, organophosphates, and also with the fungicide maneb and copper sulfate, carbofuran, hexonal, dioxin, methomyl and its salts, as well as rare cases of poisoning with the fungicide combination of propineb and cymoxanil. Headache often occurs after long term work with pesticides and/or in laboratories. There are numerous symptoms accompanying headache in pesticide poisoning the most common being elevated body temperature, lassitude, dizziness, irritability, nausea, vomiting, epigastric pain, diarrhea, myalgia, pains in the arms and legs, sleepiness, pains in joints, irritation of eyes/face/skin, sweating. Much less common are respiratory disturbances, tachycardia, tachypnea and other cardiac distur bances, fall of blood pressure, gastrointestinal discomforts, constipation, poor appetite, significant decrease in leukocyte count, anemia, albuminuria, azotemia, fasciculations, miosis, blurred vision, memory disturbances and other neurologic disturbances, postural tremor, signs of cerebral function damage, bradykinesia, etc. PMID:18710090

  18. Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.

    Science.gov (United States)

    Chen, Zhuo; Miao, Feng; Paterson, Andrew D; Lachin, John M; Zhang, Lingxiao; Schones, Dustin E; Wu, Xiwei; Wang, Jinhui; Tompkins, Joshua D; Genuth, Saul; Braffett, Barbara H; Riggs, Arthur D; Natarajan, Rama

    2016-05-24

    We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory. PMID:27162351

  19. Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.

    Science.gov (United States)

    Hale, L J; Welsh, G I; Perks, C M; Hurcombe, J A; Moore, S; Hers, I; Saleem, M A; Mathieson, P W; Murphy, A J; Jeansson, M; Holly, J M; Hardouin, S N; Coward, R J

    2013-05-01

    Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species. PMID:23299523

  20. SGLT2 Inhibitors: Glucotoxicity and Tumorigenesis Downstream the Renal Proximal Tubule?

    Science.gov (United States)

    Bertinat, Romina; Nualart, Francisco; Yáñez, Alejandro J

    2016-08-01

    At present, diabetes mellitus is the main cause of end-stage renal disease. Effective glycaemic management is the most powerful tool to delay the establishment of diabetic complications, such as diabetic kidney disease. Together with reducing blood glucose levels, new anti-diabetic agents are expected not only to control the progression but also to restore known defects of the diabetic kidney. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising anti-diabetic agents that reduce hyperglycaemia by impairing glucose reabsorption in proximal tubule of the kidney and increasing glucosuria. SGLT2 inhibitors have shown to reduce glucotoxicity in isolated proximal tubule cells and also to attenuate expression of markers of overall kidney damage in experimental animal models of diabetes, but the actual renoprotective effect for downstream nephron segments is still unknown and deserves further attention. Here, we briefly discuss possible undesired effects of enhanced glucosuria and albuminuria in nephron segments beyond the proximal tubule after SGLT2 inhibitor treatment, offering new lines of research to further understand the renoprotective action of these anti-diabetic agents. Strategies blocking glucose reabsorption by renal proximal tubule epithelial cells (RPTEC) may be protective for RPTEC, but downstream nephron segments will still be exposed to high glucose and albumin levels through the luminal face. The actual effect of constant enhanced glucosuria over distal nephron segments remains to be established. J. Cell. Physiol. 231: 1635-1637, 2016. © 2015 Wiley Periodicals, Inc. PMID:26661279

  1. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders

  2. Increased Oxidative DNA Damage in Placenta Contributes to Cadmium-Induced Preeclamptic Conditions in Rat.

    Science.gov (United States)

    Zhang, Xiaojie; Xu, Zhangye; Lin, Feng; Wang, Fan; Ye, Duyun; Huang, Yinping

    2016-03-01

    To explore the possible mechanisms of cadmium (Cd)-induced preeclamptic conditions in rats. In the present study, we introduced the in vivo model of preeclampsia by giving intraperitoneal injections of cadmium chloride (CdCl2) to pregnant rats from gestational day (GD) 4 to 19. Maternal body weights were recorded on GD 0, 14, and 20, while their systolic blood pressures (SBPs) monitored on GD 3, 11, and 18. On GD 20, rats were sacrificed and the specimens were collected. The morphological changes of placenta and kidney tissues of pregnant rats were examined by hematoxylin and eosin staining assay. Blood Cd level was detected by inductively coupled plasma mass spectrometry. Total antioxidant capacity (TAC) was evaluated using FRAP method and total nitrite (NOx) was detected with Griess reagent. Antioxidative factors and DNA damage/repair biomarkers were measured by real-time qPCR, western blot or immunohistochemistry study. The current results showed that CdCl2-treated pregnant rats developed preeclampsia (PE)-like manifestations, such as hypertension, albuminuria, with decreased TAC and increased blood Cd level, and pro-oxidative/antioxidative or DNA damage/repair biomarkers. Our study demonstrated that increased oxidative DNA damage in placenta could contribute to Cd-induced preeclamptic conditions in rat. PMID:26194818

  3. Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes

    Science.gov (United States)

    Ortega Moreno, Lorena; Lamacchia, Olga; Copetti, Massimiliano; Salvemini, Lucia; De Bonis, Concetta; De Cosmo, Salvatore; Cignarelli, Mauro; Trischitta, Vincenzo; Menzaghi, Claudia

    2015-01-01

    High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients. The association between serum adiponectin levels and estimated glomerular filtration rate (eGFR by Chronic Kidney Disease-Epidemiology Collaboration CKD-EPI equation) was investigated in 1,243 patients with T2D from two cross-sectional Italian studies: 878 from San Giovanni Rotondo (SGR) and 365 from Foggia (FG). Serum adiponectin was inversely associated with eGFR in SGR [β (standard error, SE) for 1 standard deviation (SD) of adiponectin = -3.26 (0.64)] and in FG [β(SE)=-5.70(1.28)] sample, as well as in the two studies combined [β(SE)=-3.99(0.59)];(p<0.0001 for all). In this combined analysis, the association was still significant after adjusting for sex, smoking habits, body mass index (BMI), waist circumference, diabetes duration, glycated hemoglobin (HbA1c), albumin creatinine ratio (ACR) and anti-hyperglycemic, anti-hypertensive and anti-dyslipidemic treatments [β (SE)= -2.19 (0.59), p = 0.0001]. A stronger association between each SD adiponectin increment and low eGFR was observed among patients with micro-/macro-albuminuria, as compared to those with normo-albuminuria [adjusted β(SE)=-4.42(1.16) ml/min/1.73m2 vs. -1.50 (0.67) ml/min/1.73m2, respectively; p for adiponectin-by-albuminuric status = 0.022]. For each adiponectin SD increment, the odds of having eGFR < 60 ml/min/1.73m2 increased by 41% (odds ratio, OR = 1.41; 95% confidence interval, CI 1.21–1.64) in SGR sample, 53% (OR = 1.53; 95% CI 1.21–1.94) in FG sample, and 44% (OR = 1.44; 95%CI 1.27–1.64) in the two studies considered together (p<0.0001 for all). In the combined sample, further adjustment for the

  4. Epidemiologic Investigation of Chronic Kidney Disease in Changchun Adult Male Population%长春市成年男性慢性肾脏病流行病学调查

    Institute of Scientific and Technical Information of China (English)

    李银辉; 佟丹梅; 王晶; 刘水仙; 刘宝玲; 魏宇鹏; 闫利

    2015-01-01

    Objective To investigate the prevalence and risk factors of chronic kidney disease(CKD)in Changchun adult male population . MethodsQuestionnaire(anamnesis, smoking, drink)of risk factors of CKD; Physical Examination (blood pressure, height and body mass);Kidney related testing (uromicroprotein/creatinine ratio; urine and sediment;serum creatinine; and to estimate glomerular ifltration rate). Detection of risk factors including blood sugar, blood uric acid blood lipid. Through statistical analysis , to investigate the prevalence and risk factors of CKD in Changchun adult male population .ResultsEligible data of 3694 subjects were enrolled in the study. The prevalence of albuminuria was 15.29%. reduced of eGFR was 1.32%, hematuria was 4.87%. and CKD was16.24% ,the recognition was 6.17%.Independent risk factors of albuminuria were age, hypertension, high uric acid, high cholesterol and high BMI.Independent risk factors of CKD were age, hypertension, high uric acid, high cholesterol and high BMI.Conclusions The prevalence of CKD is quite high and the recognition rate is low in Changchun adult male population. Risk factors of CKD were age, hypertension, high uric acid, high cholesterol and high BMI.%目的:探讨长春市成年男性人群中慢性肾脏病(CKD)的患病情况和相关危险因素。方法通过对长春市成年男性健康体检,进行CKD及相关危险因素的问卷调查(既往史、吸烟、饮酒等)、体格检查(血压、身高和体重质量)和肾脏相关检测(尿微量白蛋白/肌酐比值;尿常规及沉渣;血清肌酐;并估算肾小球滤过率)。同时还进行危险因素相关检测包括血糖;血尿酸;血脂水平检测。了解长春市成年男性CKD的患病情况及相关危险因素。结果在3694例资料完整的人群中,白蛋白尿的患病率为15.29%,肾功能下降的患病率为1.32%,血尿的患病率为4.87%。该人群中CKD的患病率为16.24%,知晓率为6.17%。多因

  5. Determinants of arterial stiffness in chronic kidney disease stage 3.

    Directory of Open Access Journals (Sweden)

    Natasha J McIntyre

    Full Text Available BACKGROUND: Early chronic kidney disease (CKD is associated with increased cardiovascular (CV risk but underlying mechanisms remain uncertain. Arterial stiffness (AS is associated with increased CV risk in advanced CKD, but it is unclear whether AS is relevant to CV disease (CVD in early CKD. STUDY DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: 1717 patients with previous estimated glomerular filtration rate (eGFR 59-30 mL/min/1.73 m(2; mean age 73±9y, were recruited from 32 general practices in primary care. OUTCOMES: Increased arterial stiffness. MEASUREMENTS: Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Carotid to femoral pulse wave velocity (PWV was determined as a measure of AS, using a Vicorder™ device. RESULTS: Univariate analysis revealed significant correlations between PWV and risk factors for CVD including age (r = 0.456; p<0.001, mean arterial pressure (MAP (r = 0.228; p<0.001, body mass index (r = -0.122; p<0.001, log urinary albumin to creatinine ratio (r = 0.124; p<0.001, Waist to Hip ratio (r = 0.124, p<0.001, eGFR (r = -0.074; p = 0.002, log high sensitivity c-reactive protein (r = 0.066; p = 0.006, HDL (r = -0.062; p = 0.01 and total cholesterol (r = -0.057; p = 0.02. PWV was higher in males (9.6 m/sec vs.10.3 m/sec; p<0.001, diabetics (9.8 m/sec vs. 10.3 m/sec; p<0.001, and those with previous CV events (CVE (9.8 m/s vs. 10.3 m/sec; p<0.001. Multivariable analysis identified age, MAP and diabetes as strongest independent determinants of higher PWV (adjusted R² = 0.29. An interactive term indicated that PWV increased to a greater extent with age in males versus females. Albuminuria was a weaker determinant of PWV and eGFR did not enter the model. LIMITATIONS: Data derived from one study visit, with absence of normal controls. CONCLUSION: In this cohort, age and traditional CV risk factors were

  6. Time Dependent Relative Risks in Life Insurance Medical Underwriting.

    Science.gov (United States)

    Kneepkens, Robert F

    2015-01-01

    Introduction .- Life insurance medicine focuses on mortality hazards in specified periods. People are free to insure their lives for shorter or longer terms. Because the chosen terms range from 1 year to a life time, life insurers have to take into account the fact that the predictive value of risk indicators can and will change over time. The time a risk indicator keeps its predictive value, will be dependent on its biological effects, volatility, and treatability. For a given applicant this implies that the relative hazard (RH) calculated for his/her medical condition should be dependent on the term of the insurance. The main objective of this study is to determine if some commonly used risk indicators - previously used to study age dependency of relative risks - have a predictive value that increases with the observation period. (1) Methods .- This population-based cohort study uses NHANES-data files from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES Linked Mortality Files 2010. Only participants aged 20 to 69 that were examined in mobile examination centers, without a history of some prevalent high risk diseases were included. The observed mortality was compared to the expected mortality in a Generalized Linear Model (GLM) with Poisson error structure with two reference populations, which both can serve as preferred reference for life insurers: The United States Life Tables 2008 (USLT) and the 2008 Valuation Basic Tables (VBT) based on the insured population of 35 US Life insurers. The time dependency of the RHs of the systolic blood pressure (SBP), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), serum albumin and albuminuria, was assessed, with correction for ethnicity, household income, history of diabetes mellitus, BMI and serum cholesterol. To be able to compare the results with the results of the Age Dependency Study (ADS), the same data, risk indicators, statistical analysis method, and the

  7. Acid sphingomyelinase gene knockout ameliorates hyperhomocysteinemic glomerular injury in mice lacking cystathionine-β-synthase.

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    Krishna M Boini

    Full Text Available Acid sphingomyelinase (ASM has been implicated in the development of hyperhomocysteinemia (hHcys-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs and Asm mouse gene by cross breeding Cbs(+/- and Asm(+/- mice. Given that the homozygotes of Cbs(-/-/Asm(-/- mice could not survive for 3 weeks. Cbs(+/-/Asm(+/+, Cbs(+/-/Asm(+/- and Cbs(+/-/Asm(-/- as well as their Cbs wild type littermates were used to study the role of Asm(-/- under a background of Cbs(+/- with hHcys. HPLC analysis revealed that plasma Hcys level was significantly elevated in Cbs heterozygous (Cbs(+/- mice with different copies of Asm gene compared to Cbs(+/+ mice with different Asm gene copies. Cbs(+/-/Asm(+/+ mice had significantly increased renal Asm activity, ceramide production and O(2.(- level compared to Cbs(+/+/Asm(+/+, while Cbs(+/-/Asm(-/- mice showed significantly reduced renal Asm activity, ceramide production and O(2.(- level due to increased plasma Hcys levels. Confocal microscopy demonstrated that colocalization of podocin with ceramide was much lower in Cbs(+/-/Asm(-/- mice compared to Cbs(+/-/Asm(+/+ mice, which was accompanied by a reduced glomerular damage index, albuminuria and proteinuria in Cbs(+/-/Asm(-/- mice. Immunofluorescent analyses of the podocin, nephrin and desmin expression also illustrated less podocyte damages in the glomeruli from Cbs(+/-/Asm(-/- mice compared to Cbs(+/-/Asm(+/+ mice. In in vitro studies of podocytes, hHcys-enhanced O(2.(- production, desmin expression, and ceramide production as well as decreases in VEGF level and podocin expression in podocytes were substantially attenuated by prior treatment with amitriptyline, an Asm inhibitor. In conclusion, Asm gene knockout or corresponding enzyme

  8. Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1-7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats.

    Science.gov (United States)

    Husková, Zuzana; Kopkan, Libor; Červenková, Lenka; Doleželová, Šárka; Vaňourková, Zdeňka; Škaroupková, Petra; Nishiyama, Akira; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kramer, Herbert J; Červenka, Luděk

    2016-04-01

    The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin-converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 μg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis. PMID:26833491

  9. Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators) - A pilot study

    International Nuclear Information System (INIS)

    There are no available data about the prevalence of chronic kidney disease (CKD) and its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and blood and urine samples were collected. Participants were categorized to their CKD stage according to their estimated Modification of Diet in Renal Disease (MDRD3)-based, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the presence of albuminuria. The sample comprised 491 (49.9% were males) adult Saudi nationals. The mean age was 37.4 ± 11.3 years. The overall prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mellitus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD. Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients (Author).

  10. Periodontitis predicts elevated C-reactive protein levels in chronic kidney disease.

    Science.gov (United States)

    Ioannidou, E; Swede, H; Dongari-Bagtzoglou, A

    2011-12-01

    Based on the existing evidence supporting a state of chronic inflammation in chronic kidney disease (CKD), we hypothesized that periodontal infection may affect the systemic inflammatory status of a nationally representative CKD population as measured by serum C-reactive protein (CRP). We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) dataset including 2303 individuals. We followed the American Academy of Periodontology (AAP)/Centers for Disease Control and Prevention (CDC) case definition for periodontitis. We used a cutoff point of 30% sites with (PD) ≥ 5 mm and (CAL) ≥ 4 mm to define generalized periodontitis cases. We estimated glomerular filtration rate based on cystatin C levels using the relevant equation. Urinary albumin-to-creatinine ratio was calculated in milligrams per gram with a cutoff point of 30 mg/g. CKD was defined based on eGFR < 60 mL/min/1.73 m(2) and albuminuria ≥ 30 mg/g. Periodontitis was found in 427 (12.3%) individuals. Of individuals with periodontitis, 41.8% had serum CRP higher than 0.3 mg/dL compared with 27.1% of non-periodontitis and 53.1% of edentulous individuals (p = 0.001 for all comparisons). When the extent of periodontitis was used as one of the independent variables, the parsimonious model showed a strong independent association between extent of periodontitis and serum CRP levels (OR = 2.0, CI95% = 1.2-3.6). PMID:21940520

  11. Blood pressure-independent effect of candesartan on cardio-ankle vascular index in hypertensive patients with metabolic syndrome

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    Kanako Bokuda

    2010-07-01

    Full Text Available Kanako Bokuda1, Atsuhiro Ichihara1,2, Mariyo Sakoda1, Asako Mito1, Kenichiro Kinouchi1, Hiroshi Itoh11Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Endocrinology and Anti-Aging Medicine, Keio University School of Medicine, Tokyo, JapanAbstract: Angiotensin receptor blockers (ARBs are known to reduce the cardiovascular risk in hypertensive patients. This study was designed to examine the effect of an ARB candesartan on subclinical atherosclerosis assessed by cardio-ankle vascular index (CAVI in comparison with calcium channel blockers (CCBs alone in hypertensive patients with metabolic syndrome (MetS. A total of 53 consecutive hypertensive patients with MetS were randomly assigned to the candesartan group, in which candesartan was added on, or the CCBs group, in which CCBs were added on. Clinical and biological parameters were obtained before and after the 12-month treatment period. The primary measure of efficacy was the %change in CAVI. When treated with candesartan, but not CCBs, CAVI significantly decreased from 8.7 to 7.7 by 11%. Blood pressure (BP significantly decreased with both treatments, but the differences between groups were not significant. The changes in other parameters remained unchanged in both the groups. Analysis of covariance found that both the BP reduction and the therapy difference contributed to the decrease in CAVI, but the BP reduction was not involved in the decrease in CAVI caused by the difference in the therapy. Candesartan may be a better antihypertensive drug than CCBs to that subclinical atherosclerosis of patients with MetS.Keywords: albuminuria, ambulatory blood pressure, calcium channel blockers, carotid ­intima-media thickness

  12. Evaluation of microalbuminuria in relation to asymptomatic bacteruria in Nigerian patients with sickle cell anemia

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    B A Iwalokun

    2012-01-01

    Full Text Available Studies have identified microalbuminuria (MA and asymptomatic bacteruria (ASB as co-morbid factors in sickle cell anemia (SCA. However, the relationship between these comorbid factors remains unclear and data are lacking for Nigerian patients. This study determined the prevalence of MA and ASB in a cohort of patients with SCA in a steady state, in Lagos, Nigeria. Early morning mid-stream urine samples were collected in sterile bottles from 103 patients comprising 48 males and 55 females with a mean age of 10.4 years. Aerobic culture and colony count of organisms was done using conventional methods. Serum creatinine and hematological indices, including irreversibly sickled cells (ISC, were also assayed. Of the 103 urine samples screened, 23 (22.3% had albuminuria (ALB, and consisted of nine males and 14 females (P > 0.05; 16.5% of the cases had MA (P 0.05. The prevalence of confirmed ASB was 14.6%, with females accounting for 14 of 19 probable ASB cases (P <0.05. Univariate regression analysis demonstrated a significant (P <0.05 association between age at onset of MA, hemoglobin level, reticulocyte count, ISC and occurrence of ASB, but with only ISC evolving as an independent predictor. Twenty-eight bacterial isolates predominated by Escherichia coli (39.3%; P <0.05, of whom 89.3% were multi-drug resistant, were recovered from the ASB urine samples. In conclusion, both MA and ASB are common in Nigerian SCA patients, with the former occurring from the first decade of life.

  13. Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin.

    Science.gov (United States)

    Munusamy, Shankar; do Carmo, Jussara M; Hosler, Jonathan P; Hall, John E

    2015-10-15

    We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R-/-), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R-/- mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R-/- mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R-/- mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin. PMID:26290368

  14. Circulating adipocytokines and chronic kidney disease.

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    Katherine T Mills

    Full Text Available BACKGROUND: Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD, but their relationship with CKD has not been well characterized. METHODS: We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m(2 or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors. RESULTS: Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001 and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001 were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9 for leptin and 12.7 (6.5, 24.6 for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6. In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels. CONCLUSIONS: These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

  15. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

    LENUS (Irish Health Repository)

    Luo, Xiaoyan

    2011-11-01

    Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-\\/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg\\/dl) was prevented for >6 months by the dsAAV2\\/7, dsAAV2\\/8, and dsAAV2\\/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2\\/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2\\/7 and dsAAV2\\/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2\\/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-\\/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2\\/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2\\/9 vector. Hepatorenal correction in G6pase (-\\/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

  16. Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model

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    Mi Young Lee

    2011-04-01

    Full Text Available BackgroundWhile there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.MethodsThirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5, spironolactone-treated (n=10, losartan-treated (n=9, and combination of spironolactone- and losartan-treated (n=9.ResultsAt week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.ConclusionThese results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

  17. Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

    Science.gov (United States)

    Mehdi, Uzma F.; Adams-Huet, Beverley; Raskin, Philip; Vega, Gloria L.

    2009-01-01

    Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio ≥300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, −51.0%, −11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, −37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial. PMID:19926893

  18. Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators - A pilot study

    Directory of Open Access Journals (Sweden)

    Alsuwaida Abdulkareem

    2010-01-01

    Full Text Available There are no available data about the prevalence of chronic kidney disease (CKD and its risk factors in the general population of the kingdom of Saudi Arabia. To estimate the prevalence of CKD and its associated risk factors in the Saudi population, we conducted a pilot community-based screening program in commercial centers in Riyadh, Saudi Arabia. Candidates were interviewed and blood and urine samples were collected. Participants were categorized to their CKD stage according to their estimated Modification of Diet in Renal Disease (MDRD3-based, the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation and the presence of albuminuria. The sample comprised 491 (49.9% were males adult Saudi nationals. The mean age was 37.4 ± 11.3 years. The over-all prevalence of CKD was 5.7% and 5.3% using the MDRD-3 and CKD-EPI glomerular filtration equations, respectively. Gender, age, smoking status, body mass index, hypertension and diabetes mel-litus were not significant predictors of CKD in our cohort. However, CKD was significantly higher in the older age groups, higher serum glucose, waist/hip ratio and blood pressure. Only 7.1% of the CKD patients were aware of their CKD status, while 32.1% were told that they had protein or blood in their urine and 10.7% had known kidney stones in the past. We conclude that prevalence of CKD in the young Saudi population is around 5.7%. Our pilot study demonstrated the feasibility of screening for CKD. Screening of high-risk individuals is likely to be the most cost-effective strategy to detect CKD patients.

  19. Linagliptin: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Doupis J

    2014-05-01

    Full Text Available John DoupisIatriko Palaiou Falirou Medical Center, Division of Diabetes, Athens, GreecePurpose: The nature of biomedical research affords a broad range of investigational topics at the preclinical stage, not all of which may be explored in subsequent clinical studies. To provide a comprehensive perspective on the physiologic effects of the dipeptidyl peptidase-4 inhibitor linagliptin, this review will discuss the results of both preclinical and clinical research, summarizing data describing outcomes associated with its use.Summary: Clinical studies demonstrate an overall favorable safety profile, low risk for hypoglycemia, weight neutrality, primarily nonrenal clearance, and efficacy for glycosylated hemoglobin reduction, typically ranging from 0.6% to 0.8% depending on baseline levels. In addition to these characteristics, preclinical research on linagliptin has yielded several interesting findings such as improved wound healing, reduced hepatic fat content, decreased infarct size following myocardial infarction or intracranial stroke, and improved vascular function with decreased oxidative stress. In accordance with its preclinical profile, linagliptin is unique among available dipeptidyl peptidase-4 compounds because it does not require dose adjustment when used in patients with renal dysfunction. Reduction of albuminuria with linagliptin on top of inhibitors of the renin–angiotensin–aldosterone system in both preclinical and post hoc clinical analysis serves as the foundation for ongoing clinical trials.Conclusion: In addition to its efficacy for glycemic control, current literature points to other potential opportunities associated with linagliptin therapy. These results warrant further investigation and underscore the importance of translational study based on findings from preclinical research. Moving forward, we can expect that future research on linagliptin and other incretin-based therapies will continue to expand their

  20. End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899

    Institute of Scientific and Technical Information of China (English)

    Matthias; L?hn; Oliver; Plettenburg; Aimo; Kannt; Markus; Kohlmann; Armin; Hofmeister; Dieter; Kadereit; Peter; Monecke; Alexander; Schiffer; Anke; Schulte; Hartmut; Ruetten; Yuri; Ivashchenko

    2015-01-01

    AIM: To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme(ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage. METHODS: Long-term pharmacological characterization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition and the other is insensitive [deoxycorticosterone acetate(DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension. RESULTS: Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calciumchannel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension. CONCLUSION: Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.

  1. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice.

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    Gai, Zhibo; Gui, Ting; Hiller, Christian; Kullak-Ublick, Gerd A

    2016-01-29

    Activation of the farnesoid X receptor (FXR) has indicated a therapeutic potential for this nuclear bile acid receptor in the prevention of diabetic nephropathy and obesity-induced renal damage. Here, we investigated the protective role of FXR against kidney damage induced by obesity in mice that had undergone uninephrectomy, a model resembling the clinical situation of kidney donation by obese individuals. Mice fed a high-fat diet developed the core features of metabolic syndrome, with subsequent renal lipid accumulation and renal injury, including glomerulosclerosis, interstitial fibrosis, and albuminuria. The effects were accentuated by uninephrectomy. In human renal biopsies, staining of 4-hydroxynonenal (4-HNE), glucose-regulated protein 78 (Grp78), and C/EBP-homologous protein, markers of endoplasmic reticulum stress, was more prominent in the proximal tubules of 15 obese patients compared with 16 non-obese patients. In mice treated with the FXR agonist obeticholic acid, renal injury, renal lipid accumulation, apoptosis, and changes in lipid peroxidation were attenuated. Moreover, disturbed mitochondrial function was ameliorated and the mitochondrial respiratory chain recovered following obeticholic acid treatment. Culturing renal proximal tubular cells with free fatty acid and FXR agonists showed that FXR activation protected cells from free fatty acid-induced oxidative stress and endoplasmic reticulum stress, as denoted by a reduction in the level of reactive oxygen species staining and Grp78 immunostaining, respectively. Several genes involved in glutathione metabolism were induced by FXR activation in the remnant kidney, which was consistent with a decreased glutathione disulfide/glutathione ratio. In summary, FXR activation maintains endogenous glutathione homeostasis and protects the kidney in uninephrectomized mice from obesity-induced injury. PMID:26655953

  2. Evaluation on changes of early renal function in patients with diabetic nephropathy with contrast-enhanced ultrasound and its clinical significance

    International Nuclear Information System (INIS)

    Objective: To quantitatively assess the parameter alteration of renal blood flow in patients with diabetic nephropathy (DN) with the contrast-enhanced ultrasound (CEUS), and to evaluate value of the technique in diagnosis of early renal function changes of DN patients. Methods: 40 diabetic patients were equally divided into two group according to Mogensen's staging criteria: normal albuminuria group (group Ⅰ) and early DN group (group Ⅱ); and 15 cases of healthy volunteers were used as control group (N group) (n=15). All subjects were performed renal CEUS perfusion imaging, and QontraXt image analysis software was applied to select the region of interest (ROI) in the renal cortex. Then the time intensity curve (TIC) and kidney blood perfusion parameters were collected. Results: The renal blood perfusion was clearly shown in real time CEUS; compared with N group, the time to peak (TTP), regional blood volume (RBV), and mean transit time (MTT) of the patients in group Ⅰ were increased, there were significant differences (P<0.05); but there were no significant differences of derived peak intensity (DPI) and regional blood flow (RBF) between two groups (P>0.05). Compared with group Ⅰ and N group, the RBV, TTP and MTT of the patients were increased, the DPI and RBF were reduced in group Ⅱ, there were significant differences (P<0.05). Conclusion: The CEUS technical analysis can be used in evaluating renal abnormality of the DN patients in early period by showing the changes of renal perfusion parameters. (authors)

  3. Serum Lipid Profiles, Lipid Ratios and Chronic Kidney Disease in a Chinese Population

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    Liying Zhang

    2014-07-01

    Full Text Available Aim: To examine the association of serum lipids, lipid ratios with Chronic Kidney Disease (CKD in a Chinese population. Methods: Data were drawn from a cross-sectional survey in China. CKD was defined as estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2 or albuminuria-to-creatinine ratio (ACR > 30 mg/g. Multivariable logistic regressions and multivariate regression models were used. Serum lipids and lipid ratios included total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio. Results: In men, only logarithm-transformed (log TG was associated with CKD. The odds ratio (every SD increment was 1.39 (95% CI 1.03–1.87, P = 0.03. In women, none of the serum lipids and lipid ratios was associated with CKD. Using multivariate regression models, it was shown that log TG and log TG/HDL-C were negatively correlated with eGFR (P < 0.05 in men and LDL-C and log LDL-C/HDL-C ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05. All of serum lipid profiles and lipid related ratio were not correlated with ACR in women. Conclusion: Serum TG is the only suitable predictor for CKD in men. However, in women, none of serum lipids and lipid ratio can be used as a predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in both genders.

  4. Peripheral arterial disease among adult diabetic patients attending a large outpatient diabetic clinic at a national referral hospital in Uganda: a descriptive cross sectional study.

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    Raymond Mbayo Mwebaze

    Full Text Available BACKGROUND: Peripheral arterial disease (PAD is one of the recognised diabetic macro vascular complications. It is a marker of generalised systemic atherosclerosis and is closely associated with symptomatic coronary and cerebrovascular disease, hence significant morbidity and mortality. Among African adult diabetic populations, screening and diagnosis of PAD is frequently suboptimal. The aim of this study was to determine the prevalence and associated clinical factors of PAD in adult ambulatory diabetic patients attending the outpatient diabetic clinic of Mulago national referral and teaching hospital, Kampala Uganda. METHODS: In this descriptive cross sectional study, 146 ambulatory adult diabetic patients were studied. Information about their socio-demographic and clinical characteristics, fasting lipid profile status, blood pressure, glycated haemoglobin (HbA1c levels and presence of albuminuria was collected using a pre tested questionnaire. Measurement of ankle brachial index (ABI to assess for PAD, defined as a ratio less than 0.9 was performed using a portable 5-10 MHz Doppler device. Clinical factors associated with PAD were determined by comparing specific selected characteristics in patients with PAD and those without. RESULTS: The mean age/standard deviation of the study participants was 53.9/12.4 years with a male predominance (75, 51.4%. PAD was prevalent in 57 (39% study participants. Of these, 34 (59.6% had symptomatic PAD. The noted clinical factors associated with PAD in this study population were presence of symptoms of intermittent claudication and microalbuminuria. CONCLUSIONS: This study documents a high prevalence of PAD among adult ambulatory Ugandan diabetic patients. Aggressive screening for PAD using ABI measurement in adult diabetic patients should be emphasised in Uganda especially in the presence of symptoms of intermittent claudication and microalbuminuria.

  5. Hyperuricemia-induced NLRP3 activation of macrophages contributes to the progression of diabetic nephropathy.

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    Kim, Su-Mi; Lee, Sang-Ho; Kim, Yang-Gyun; Kim, Se-Yun; Seo, Jung-Woo; Choi, Young-Wook; Kim, Dong-Jin; Jeong, Kyung-Hwan; Lee, Tae-Won; Ihm, Chun-Gyoo; Won, Kyu-Yeoun; Moon, Ju-Young

    2015-05-01

    IL-1β-secreting nucleotide-binding oligomerization domain protein 3 (NLRP3) inflammasomes play a pivotal role in triggering innate immune responses in metabolic disease. We investigated the role of soluble uric acid in NLRP3 inflammasome activation in macrophages to demonstrate the effect of systemic hyperuricemia on progressive kidney damage in type 2 diabetes. THP-1 cells, human acute monocytic leukemia cells, were cultured to obtain macrophages, and HK-2 cells, human renal proximal tubule cells, were cultured and stimulated with uric acid. In vivo, we designed four rat groups as follows: 1) Long-Evans Tokushima Otsuka (LETO); 2) Otsuka Long-Evans Tokushima Fatty (OLETF); 3) OLETF+high-fructose diet (HFD) for 16 wk; and 4) OLETF+HFD+allopurinol (10 mg/dl administered in the drinking water). Soluble uric acid stimulated NLRP3 inflammasomes to produce IL-1β in macrophages. Uric acid-induced MitoSOX mediates NLRP3 activation and IL-1β secretion. IL-1β from macrophages activates NF-κB in cocultured proximal tubular cells. In vivo, intrarenal IL-1β expression and macrophage infiltration increased in HFD-fed OLETF rats. Lowering the serum uric acid level resulted in improving the albuminuria, tubular injury, macrophage infiltration, and renal IL-1β (60% of HFD-fed OLETF) independently of glycemic control. Direct activation of proximal tubular cells by uric acid resulted in (C-X-C motif) ligand 12 and high mobility group box-1 release and accelerated macrophage recruitment and the M1 phenotype. Taken together, these data support direct roles of hyperuricemia in activating NLRP3 inflammasomes in macrophages, promoting chemokine signaling in the proximal tubule and contributing to the progression of diabetic nephropathy through cross talk between macrophages and proximal tubular cells. PMID:25651569

  6. Podocytes degrade endocytosed albumin primarily in lysosomes.

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    Carson, John M; Okamura, Kayo; Wakashin, Hidefumi; McFann, Kim; Dobrinskikh, Evgenia; Kopp, Jeffrey B; Blaine, Judith

    2014-01-01

    Albuminuria is a strong, independent predictor of chronic kidney disease progression. We hypothesize that podocyte processing of albumin via the lysosome may be an important determinant of podocyte injury and loss. A human urine derived podocyte-like epithelial cell (HUPEC) line was used for in vitro experiments. Albumin uptake was quantified by Western blot after loading HUPECs with fluorescein-labeled (FITC) albumin. Co-localization of albumin with lysosomes was determined by confocal microscopy. Albumin degradation was measured by quantifying FITC-albumin abundance in HUPEC lysates by Western blot. Degradation experiments were repeated using HUPECs treated with chloroquine, a lysosome inhibitor, or MG-132, a proteasome inhibitor. Lysosome activity was measured by fluorescence recovery after photo bleaching (FRAP). Cytokine production was measured by ELISA. Cell death was determined by trypan blue staining. In vivo, staining with lysosome-associated membrane protein-1 (LAMP-1) was performed on tissue from a Denys-Drash trangenic mouse model of nephrotic syndrome. HUPECs endocytosed albumin, which co-localized with lysosomes. Choloroquine, but not MG-132, inhibited albumin degradation, indicating that degradation occurs in lysosomes. Cathepsin B activity, measured by FRAP, significantly decreased in HUPECs exposed to albumin (12.5% of activity in controls) and chloroquine (12.8%), and declined further with exposure to albumin plus chloroquine (8.2%, p<0.05). Cytokine production and cell death were significantly increased in HUPECs exposed to albumin and chloroquine alone, and these effects were potentiated by exposure to albumin plus chloroquine. Compared to wild-type mice, glomerular staining of LAMP-1 was significantly increased in Denys-Drash mice and appeared to be most prominent in podocytes. These data suggest lysosomes are involved in the processing of endocytosed albumin in podocytes, and lysosomal dysfunction may contribute to podocyte injury and

  7. Gender difference and relationship of insulin resistance with microalbuminuria type-2 diabetes

    International Nuclear Information System (INIS)

    To determine the relationship of insulin resistance with microalbuminuria in patients of type-2 Diabetes mellitus and observe gender difference if any. Study Design: A cross-sectional study. Place and Duration of Study: Diabetes Clinic of Combined Military Hospital, Malir Cantt, from April to August 2007. Methodology: One hundred and fifty five patients of type-2 Diabetes mellitus were included in the study who had either microalbuminuria or normo albuminuria. Body mass index, waist circumference and blood pressure were recorded. Fasting venous blood sample was collected for plasma glucose (FPG), serum insulin, total and HDL cholesterol, triglycerides, creatinine and HbA1c. Urine albumin excretion was determined using urine albumin to creatinine ratio. Insulin resistance was calculated from fasting plasma glucose and serum insulin levels, using homeostatic model assessment of insulin resistance (HOMA-IR). Correlation and association testing was carried out with significance at p < 0.05. Results: Microalbuminuria was found to be significantly correlated with HOMA-IR (r = 0.33, p < 0.001), serum insulin (r = 0.28, p = < 0.001), body mass index (r = 0.18, p = 0.02) and waist circumference (r = 0.21, p = 0.008). This correlation was more significant in women (n = 85, r = 0.48, p = < 0.0001) as compared to men (n = 70, r = 0.14, p = 0.12). The correlation between HOMA-IR and urine albumin excretion remained highly significant (p = 0.001) after controlling for gender, age, duration of diabetes, waist circumference, hypertension, triglycerides and HbA1c. Conclusion: Urinary albumin excretion in patients of type-2 diabetes is strongly associated with insulin resistance and related cardiovascular risk factors. This association appears to be stronger in women than the men, in our population. (author)

  8. TO STUDY THE SERUM LEVELS OF HSCRP IN PRE-DIABETES MELLITUS PATIENTS & TO COMPARE THAT OF NORMAL SUBJECTS

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    Ravish

    2015-12-01

    Full Text Available BACKGROUND Diabetes Complications is one of the major long-term complications of diabetes mellitus. Previous studies have proved that Type 2 Diabetes is frequently associated with an inflammatory status with increased levels of serum hsCRP, an inflammatory marker, but little information is available on the relationship between low-grade inflammation and diabetic early complications. OBJECTIVES 1. To determine the serum level of hsCRP in Type-2 Pre diabetics patients with and without early diabetic complications and to compare with that of normal subjects. 2. To study the association of serum hsCRP levels with glycosylated haemoglobin and AC ratio. METHODOLOGY 56 Type 2 Pre Diabetic patients in the age range of 50-60 years with >10years of duration of diabetes were recruited. Diabetic patients were divided into 2 groups, diabetic patients with AC ratio between 30-300 mg/gm and diabetic patients with AC ratio >300mg/gm. 24age and sex matched normal subjects were recruited for this study. Serum hsCRP levels were measured by turbidometry method. RESULTS There was a significant increase in serum hsCRP levels in both the diabetic groups (mean=4.77±3.95 compared to normal controls (mean=2.35±2.64. The hsCRP levels showed a positive correlation with HbA1c (r =0.38, p=0.007 and AC ratio (r= 0.33, p=0.01 in diabetic patients. CONCLUSION Serum hsCRP is increased in prediabetes patients and correlates with HbA1c and albuminuria. Thus, estimation of serum hsCRP levels helps in early intervention and prevention of further complications in diabetic prediabetes patients.

  9. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

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    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  10. The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

    Science.gov (United States)

    Davies, Melanie; Chatterjee, Sudesna; Khunti, Kamlesh

    2016-01-01

    Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of

  11. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  12. The influence of nutrition (diet treatment in streptozotocin – induced diabetic rats

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    Chrcheva-Nikolovska Radmila

    2013-07-01

    Full Text Available The present study was designated to evaluate the effect of special antidiabetic diet treatment upon oxidative stress parameters in the initial stages of the development of diabetes. Male Wistar strain rats were used as an experimental model, divided into five groups: group 1, control rats; group 2, antidiabetic diet group; group 3, rats with induced diabetes mellitus – diabetic control; group 4, rats with induced diabetes mellitus and diet food, and group 5, rats with induced diabetes mellitus and insulin treatment.A significant decrease in superoxide dismutase (SOD and total glutathione (GSH activities were observed in the liver of diabetic rats when compared with control animals. There was simple evidence that elevation in glucose concentration depress natural antioxidant defense such as SOD and GSH. The observed decrease in SOD activity could result from inactivation by H2O2 or by glycation of the enzyme, which have been reported to occur in diabetes. The possible source of oxidative stress in diabetes includes shifts in redox balance resulting from altered carbohydrate and lipid metabolism, increased generation of reactive oxygen species, and decreased level of antioxidant defences such as GSH and SOD. The plasma level of aminotransferases (ALT, AST, creatine kinase (CK, lactate dehydrogenase (LDH and urea were significantly increased after induction of diabetes, in all groups under treatment. In contrast, rats fed special diet food, have shown slight different, but not significant changes. The decrease in total protein and albumin fraction may be due to microproteinuria and albuminuria, which are important clinical markers of diabetic nephro­pathy, and­/or may be due to increased protein catabolism.The findings of the present study suggest that special diet formula useful for prevention of progressive hyperglycaemia in age induced diabetes in dogs, could not restore the imbalance of cellular defence mechanism provoked by streptozotocin.

  13. Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

    Science.gov (United States)

    Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

    2016-05-01

    Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations. PMID:27083286

  14. Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy.

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    Alaa Alkhalaf

    Full Text Available BACKGROUND: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN, urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66. Controls were matched for gender and diabetes duration (n = 82. METHODOLOGY/PRINCIPAL FINDINGS: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS. Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978. Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. CONCLUSIONS: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.

  15. Protein-induced changes in kidney function depend on the time of administration but not on the dietary source.

    Science.gov (United States)

    Buzio, C; Mutti, A; Perazzoli, F; Alinovi, R; Arisi, L; Negro, A

    1990-01-01

    Two separate experiments were carried out to study the effects of the same acute protein load given at different hours of the day and to assess the ability of proteins from different sources to induce hyperfiltration. In the first experiment, 9 healthy volunteers were kept at strict bedrest for 48 h, during which both a meat high-protein meal (protein load, PL) and a vegetable low-protein meal (control load, CL) were given either at lunch or at suppertime. As compared to a CL, PL determined a significant increase in GFR, total proteinuria (uTP), albuminuria (uA), and urinary retinol-binding protein (uRBP). These effects were much more significant after lunch PL than after supper PL, thus indicating an interaction between the PL and the time of the day. The existence of a circadian rhythm for GFR, uTP, uA, and uRBP was corroborated by spontaneous changes over baseline levels, which also were prominent after lunch CL as compared to those following supper CL. In the second experiment, 7 healthy volunteers ingested at lunch three protein-rich meals at 1-week intervals. The three protein loads consisted of about 80 g protein in the form of cooked red meat, cheese, and soya, respectively. The only significant differences between groups were urea appearance and urea clearance, lower and higher, respectively after soya load. These findings suggest that when evaluating the renal functional reserve after acute protein load both the spontaneous changes and the time-dependent sensitivity of kidney functions to acute challenges should be considered. Finally, the amount rather than quality of dietary proteins seems to be the determinant factor for protein-induced glomerular hyperfiltration. PMID:2077404

  16. Risk factors for the development of diabetic nephropathy

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    Antić Miodrag

    2009-01-01

    Full Text Available Introduction. Results of epidemiological analysis show that one third of patients with diabetes mellitus develop diabetic nephropathy (DN. Strategies used until now to slow down the progression of DN were initiated when the symptoms of DN were already present. Objective. Our objective was to analyze the prevalence and characteristics of DN and to determine the factors leading to DN. Methods. Fifty-two patients with diabetes mellitus (DM - 32 with type 1 aged 32 years and 20 with type 2 aged 59 years - were referred from the Institute of Endocrinology, Diabetes and Metabolic Diseases to the Department of Nephrology for kidney function evaluation. Apart from routine laboratory analyses, glomerular filtration rate was calculated using the MDRD formula (modification of diet in renal disease, the size of the kidney was measured by ultrasound, and kidney volume was calculated using the ellipsoid formula. Results Thirty percent of the patients revealed normal (eight patients with DM type 1 or satisfactory kidney function (eight patients with DM type 1 with physiological proteinuria. Micro-albuminuria (MAU or pathological proteinuria (PRT were found in 10 and 9 patients, respectively, with DM type 1, while decreased kidney function was found in one patient without proteinuria. MAU or PRT were found in four and eight patients, respectively, with DM type 2 and decreased kidney function in four patients without proteinuria. Kidney function was significantly lower in patients with DM type 2 in comparison to DM type 1, while the patients with decreased kidney function had a higher PRT. Compared to DM type 2, in DM type 1 patients, the kidney was longer, and parenchymal artery resistance index was lower in DM type 1 patients compared to DM type 2. Factors associated with DN were patient's age, duration of diabetes, systolic blood pressure, HbA1c and kidney volume. Conclusion. The prevalence of DN among the studied patients was 70%. Treatable factors

  17. C-peptide as a Therapy for Kidney Disease: A Systematic Review and Meta-Analysis.

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    James A Shaw

    Full Text Available C-peptide has intrinsic biological activity and may be renoprotective. We conducted a systematic review to determine whether C-peptide had a beneficial effect on renal outcomes. MEDLINE, EMBASE, and the Cochrane Central Databases were searched for human and animal studies in which C-peptide was administered and renal endpoints were subsequently measured. We identified 4 human trials involving 74 patients as well as 18 animal studies involving 35 separate experiments with a total of 641 animals. In humans, the renal effects of exogenously delivered C-peptide were only studied in type 1 diabetics with either normal renal function or incipient nephropathy. Pooled analysis showed no difference in GFR (mean difference, -1.36 mL/min/1.73 m2, p = 0.72 in patients receiving C-peptide compared to a control group, but two studies reported a reduction in glomerular hyperfiltration (p<0.05. Reduction in albuminuria was also reported in the C-peptide group (p<0.05. In diabetic rodent models, C-peptide led to a reduction in GFR (mean difference, -0.62 mL/min, p<0.00001 reflecting a partial reduction in glomerular hyperfiltration. C-peptide also reduced proteinuria (mean difference, -186.25 mg/day, p = 0.05, glomerular volume (p<0.00001, and mesangial matrix area (p<0.00001 in diabetic animals without affecting blood pressure or plasma glucose. Most studies were relatively short-term in duration, ranging from 1 hour to 3 months. Human studies of sufficient sample size and duration are needed to determine if the beneficial effects of C-peptide seen in animal models translate into improved long-term clinical outcomes for patients with chronic kidney disease. (PROSPERO CRD42014007472.

  18. Novel drugs and intervention strategies for the treatment of chronic kidney disease.

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    Lambers Heerspink, Hiddo Jan; de Zeeuw, Dick

    2013-10-01

    Chronic kidney disease (CKD) is a worldwide health problem. The disease is most often progressive of nature with a high impact on patients and society. It is increasingly recognized that CKD can be detected in the early stages and should be managed as early as possible. Treatment of the cause, but in particular control of the main risk markers, such as high blood pressure, glucose and albuminuria, has been instrumental in delaying the progression to end-stage renal disease (ESRD). However, despite the state of the art therapy, the absolute risk of renal and cardiovascular morbidity and mortality in CKD patients remains devastatingly high. Novel drugs are therefore highly desirable to halt effectively the progressive renal (and cardiovascular) function loss. Recently, several novel strategies have been tested targeting traditional risk factors such as blood pressure (combination therapy of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) and novel mineralocorticoid receptor antagonists) as well as dyslipidaemia (statins) with surprising results. In addition, drug targets specifically related to the kidney, such as vitamin D, uric acid, erythropoietin and phosphate, have been the subject of clinical trials, in some instances with unexpected results. Finally, novel targets including endothelin receptors and inflammatory pathways are increasingly explored as potential avenues to improve renal and cardiovascular protection, albeit that the drugs tested have not been unequivocally successful. In this article we review novel drugs or intervention strategies for the management of CKD, we try to provide explanations for the failure of some promising drugs and hypothesize on the potential success of new strategies. PMID:23802504

  19. Assessment of microalbuminuria for early diagnosis and risk prediction in dengue infections.

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    Nguyen Thi Hanh Tien

    Full Text Available BACKGROUND: Dengue is the most important arboviral infection of humans. Following an initial febrile period, a small proportion of infected patients develop a vasculopathy, with children at particular risk for severe vascular leakage and shock. Differentiation between dengue and other common childhood illnesses is difficult during the early febrile phase, and risk prediction for development of shock is poor. The presence of microalbuminuria is recognized as a useful early predictor for subsequent complications in a number of other disorders with vascular involvement. Significant proteinuria occurs in association with dengue shock syndrome and it is possible that early-phase microalbuminuria may be helpful both for diagnosis of dengue and for identification of patients likely to develop severe disease. METHODOLOGY/PRINCIPAL FINDINGS: We measured formal urine albumin to creatinine ratios (UACRs in daily samples obtained from a large cohort of children with suspected dengue recruited at two outpatient clinics in Ho Chi Minh City, Vietnam. Although UACRs were increased in the 465 confirmed dengue patients, with a significant time trend showing peak values around the critical period for dengue-associated plasma leakage, urine albumin excretion was also increased in the comparison group of 391 patients with other febrile illnesses (OFI. The dengue patients generally had higher UACRs than the OFI patients, but microalbuminuria, using the conventional cutoff of 30 mg albumin/g creatinine discriminated poorly between the two diagnostic groups in the early febrile phase. Secondly UACRs did not prove useful in predicting either development of warning signs for severe dengue or need for hospitalization. CONCLUSION/SIGNIFICANCE: Low-level albuminuria is common, even in relatively mild dengue infections, but is also present in many OFIs. Simple point-of-care UACR tests are unlikely to be useful for early diagnosis or risk prediction in dengue endemic areas.

  20. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy.

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    Hathaway, Catherine K; Chang, Albert S; Grant, Ruriko; Kim, Hyung-Suk; Madden, Victoria J; Bagnell, C Robert; Jennette, J Charles; Smithies, Oliver; Kakoki, Masao

    2016-02-23

    Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease. PMID:26858454

  1. Sexual dimorphism in renal heme-heme oxygenase system in the streptozotocin diabetic rats.

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    Bonacasa, Bárbara; Pérez, Cayetano; Salom, Miguel G; López, Bernardo; Sáez-Belmonte, Fara; Martinez, Pedro; Casas, Teresa; Fenoy, Fráncisco J; Rodriguez, Francisca

    2013-01-01

    Heme Oxygenase (HO) -1 and -2 exert antioxidant, cytoprotective and vascular actions in male diabetic rats. However, there is no information about the expression and functional significance of the renal HO system in diabetic females. The present study tested the hypothesis that the HO system is differentially regulated in the kidney of female Sprague Dawley diabetic rats, protecting it from nitrosative and glomerular functional damage. Two weeks after the administration of streptozotocin (STZ; 65 mg/kg. i.p), males (DM) and females (DF) showed hyperglycemia, polyuria and elevated kidney/body weight ratio, compared to their control males (CM) and females (CF). In conscious animals, creatinine clearance was higher (0.5 ± 00 vs. 0.3 ± 00; ml/min/100g BW; pSnMP 40 mol/kg, i.v.) induced a greater renal vasoconstrictor response in DF than in DM. Western blot analysis of renal tissue revealed higher renal cortex HO-1 protein levels in DF compared to all other groups; by immunohistochemistry this induction of HO-1 in DF was localized in tubular segments and glomeruli. Furthermore, renal cortical concentration of nitrosylated protein was higher in DM than in DF animals and inversely related with HO-1 levels in both renal cortex and medulla. These data demonstrate that the HO-1 protein is induced in females, associated with renal vasodilation, decreased renal nitrosative stress and reduced albuminuria, indicating that the HO system is protecting the kidney from diabetes-induced damage specifically in females. PMID:23092315

  2. Microalbuminuria in diabetic patients: prevalence and putative risk factors

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    Deepak Parchwani, S.P. Singh

    2011-01-01

    Full Text Available Microalbuminuria refers to the excretion of albumin in the urine at a rate that exceeds normal limits but is less than the detection level for traditional dipstick methods and is considered as a marker of diabetic nephropathy. The current study was conducted to establish the prevalence of elevated urinary albumin levels (microalbuminuria in a sequential sample of diabetic patients attending hospital diabetic clinics and to determine its relationship with known and putative risk factors, to identify micro- and normoalbuminuric patients in this sample for subsequent comparison of clinical characteristics of the micro- and normoalbuminuric patients identified and to ascertain relationship of serum angiotensin converting enzyme (ACE activity with diabetic incipient nephropathy. This cross-sectional analytical study was conducted at Gujarat Adani Institute of Medical Sciences Bhuj(Gujarat.Patients having clinical albuminuria and with other causes of proteinuria were excluded. Data was analyzed by SPSS software. Microalbuminuria was observed in 34.48% in patients with type 1 and 28.33% in patients with type 2 diabetes mellitus respectively. There was no statistically significant difference in the frequency of microalbuminuria between type 1 and type 2 diabetes mellitus patients. Having the condition was significantly associated with advanced age, poor glycaemic control, dyslipidemia (with respect to total cholesterol, triglycerides and LDL-C, smoking, body mass index and coexisting hypertension. The duration of diabetes was a significant correlate in type 1 DM subjects only. No significant association with gender, HDL-C levels, age at onset of DM, mode of treatment, socio-economic status and other lifestyle variations was found. All clinical and biochemical parameters in patient with microalbuminuria was more adversely affected than patients with normoalbuminuria. Serum angiotensin converting enzyme (ACE levels were significantly elevated (P<0.001 in

  3. Potentiation of cadmium nephrotoxicity by acetaminophen

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    Bernard, A.M.; Russis, R. de; Ouled Amor, A.; Lauwerys, R.R.

    1988-10-01

    The possible interactions between acetaminophen and cadmium (Cd) on the kidney were investigated in female Sprague-Dawley rats. Acetaminophen was administered in the food at an average dose of 900 mg/kg and Cd in drinking water at the concentration of 200 ppm. The treatment with acetaminophen and Cd lasted 2 and 10 months, respectively. No interaction between Cd and acetaminophen was observed during the period of their concomitant administration: the increase in albuminuria caused by Cd and acetaminophen was additive, while the tubular impairment caused by acetaminophen (increased ..beta../sub 2/-microglobulinuria and decreased kidney concentrating ability) was not exacerbated by Cd. None of these treatments affected the glomerular filtration rate. Four months after the end of acetaminophen treatment, the renal changes had almost completely disappeared in the rats which had received the analgesic alone. Those continously exposed to Cd had developed slight tubular damage, as evidenced by an increased urinary excretion of ..beta../sub 2/-microglobulin and ..beta..-N-acetylglucosaminidase. By contrast, rats pretreated with acetaminophen for 2 months and exposed to Cd showed a marked increase in urinary excretion of albumin and ..beta../sub 2/-microglobulin, suggesting an interaction between both treatments. At the end of the study, only the interaction with ..beta../sub 2/-microglobulin excretion was still evident; that with the urinary excretion of ..beta..-N-acetylglucosaminidase and albumin having been masked by the chronic progessive nephrosis affecting most animals at that stage. As acetaminophen had no effect on the renal accumulation of Cd, it may be concluded that pretreatment with this analygesic at a dose causing slight tubular dysfunction renders rat kidney more sensitive to the nephrotoxic action of Cd. This observation may be of clinical relevance for population groups occupationally or environmentally exposed to Cd.

  4. ENDOTHELIAL-TROPIC AND NEPHROPROTECTIVE EFFECTS OF COMBINED ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

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    M. E. Statsenko

    2015-09-01

    Full Text Available Aim. To assess the effect of the 24-week antihypertensive therapy with fixed-dose drug combination (lisinopril plus amlodipine on endothelial dysfunction and renal function in patients with arterial hypertension (HT and diabetes mellitus (DM type 2.Material and methods. 30 hypertensive patients with DM type 2 (aged 40-65 years were included into the study. Endothelial function (plasma and vascular components and renal function were studied.Results. Combined antihypertensive therapy significantly improved parameters of endothelial function in patients with HT and DM type 2: production of nitric oxide (NO in blood serum and urine increased by 122.8% and 65.8%, respectively. Along with these secretion of endothelin (ET-1 in serum and urine decreased by 26.1% and by 76.1%, respectively, p<0.05. A statistically significant redistribution of patients by type of microcirculation was established: the share of patients with normal type of microcirculation increased by 73.4%. There was a statistically significant reduction of proteinuria and albuminuria by 58% and 43.6%, respectively. The share of patients with chronic kidney disease with an estimated GFR 30-60 ml/min/1.73 m2 decreased by 16.7%.Conclusions. It has been shown that the prescription of a long-term antihypertensive therapy with dose-fixed combination (lisinopril plus amlodipine is safe and effective for endothelial function improvement, including renal endothelium, with no negative effect on glucose and lipid metabolism in patients with HT and DM type 2.

  5. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway.

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    Kuo-Feng Hua

    Full Text Available Renal reactive oxygen species (ROS and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation of IgA nephropathy (IgAN, which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L. Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1 reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2 inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3 decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4 inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5 inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

  6. A molecular signature of proteinuria in glomerulonephritis.

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    Heather N Reich

    Full Text Available Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 "albumin-regulated genes" differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25 could be distinguished from those of control subjects (n = 6 based solely upon the expression of these 231 "albumin-regulated genes." The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33 can be distinguished from controls (n = 21 based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.

  7. The goal of blood pressure in the hypertensive patient with diabetes is defined: now the challenge is go from recommendations to practice.

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    Lopez-Jaramillo, Patricio; Lopez-Lopez, Jose; Lopez-Lopez, Cristina; Rodriguez-Alvarez, Miguel I

    2014-01-01

    The recent Latin American and European guidelines published this year has proposed as a goal for blood pressure control in patients with diabetes type 2 a value similar or inferior to 140/90 mmHg. High blood pressure is the leading cause of cardiovascular diseases and deaths globally. Although once hypertension is detected, 80% of individuals are on a pharmacologic therapy only a minority is controlled. Diabetes also is a risk factor for other serious chronic diseases, including cardiovascular disease. Whether specifically targeting lower fasting glucose levels can reduce cardiovascular outcomes remains unknown. Hypertension is present in 20% to 60% of patients with type 2 diabetes, depending on age, ethnicity, obesity, and the presence of micro or macro albuminuria. High blood pressure substantially increases the risk of both macro and micro vascular complications, doubling the risk of all-cause mortality and stroke, tripling the risk of coronary heart disease and significantly hastening the progression of diabetic nephropathy, retinopathy, and neuropathy. Thus, blood pressure lowering is a major priority in preventing cardiovascular and renal events in patients with diabetes and hypertension. During many years the BP goals recommended in patients with diabetes were more aggressive than in patients without diabetes. As reviewed in this article many clinical trials have demonstrated not only the lack of benefits of lowering the BP below 130/80 mmHg, but also the J-shaped relationship in DM patients. Overall we discuss the importance of define the group of patients in whom significant BP reduction could be particularly dangerous and, on the other hand, those with a high risk of stroke who could benefit most from an intensive hypotensive therapy. In any case, the big challenge now is avoid the therapeutic inertia (leaving diabetic patients with BP values of 140/90 mmHg or higher) at all costs, as this would lead to an unacceptable toll in terms of human lives

  8. Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria

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    Mitra Basiratnia

    2012-01-01

    Full Text Available Diabetes mellitus (DM is now considered as the major cause of end-stage kidney failure, and hypertension (HTN is one of the main determinants of progression of renal disease. The aim of this study was to assess the role of blood pressure (BP by ambulatory blood pressure monitoring (ABPM in children and adolescents with type-1 DM and its correlation with micro-albuminuria (MA and diabetic control. Eighty-one patients with type-1 DM (mean age 13 ± 4 years, whose duration of DM was at least two years, were enrolled in this study. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN 11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN 30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were 33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4% had masked HTN, and 3.7% had white coat HTN. The pre-valence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. There was no correlation bet-ween HTN and both MA and HbA 1 c; also, no correlation was found between the duration of dia-betes and HbA 1 c. Moreover, no significant correlation was found between the duration of diabetes and MA (P = 0.080. Despite the high prevalence of abnormal BP profile among diabetic children, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have an impact on the progression to diabetic nephropathy, are recommended.

  9. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

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    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  10. Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced Nephropathy.

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    Min, Hye Sook; Cha, Jin Joo; Kim, Kitae; Kim, Jung Eun; Ghee, Jung Yeon; Kim, Hyunwook; Lee, Ji Eun; Han, Jee Young; Jeong, Lak Shin; Cha, Dae Ryong; Kang, Young Sun

    2016-09-01

    The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria. PMID:27510383

  11. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

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    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  12. Prevalence of chronic kidney disease and prediabetes and associated risk factors: a community-based screening in Zhuhai, Southern China

    Institute of Scientific and Technical Information of China (English)

    GU Dong-feng; SHI Yan-lin; CHEN You-ming; LIU Hong-mei; DING Ya-nan; LIU Xin-yu; LI Yong-qiang

    2013-01-01

    Background The prevalence of chronic kidney disease (CKD) and prediabetes has increased in China,and at different rates in different locations.Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes,and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.Methods A total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method.An estimated glomerular filtration rate (eGFR),albuminuria,fasting plasma glucose (FPG),and homeostatic model assessment of insulin resistance (HOMA-IR) were measured.Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006.Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes,and association of insulin resistance (IR) with CKD and prediabetes was analyzed.Results The age-standardized prevalence of CKD was 12.5%,eGFR <60 ml.min-1.1.73 m-2 was 2.7% and ACR (albumin to creatinine ratio) >30 mg/g was 10.3%.The age-standardized prevalence of prediabetes was 12.1%.Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes.Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.Conclusion CKD and prediabetes have become a major public health problem in Zhuhai,Southern China; insulin resistance may be an important risk factor.

  13. Documento de consenso para la detección y manejo de la enfermedad renal crónica

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    Alberto Martínez-Castelao

    2014-11-01

    Full Text Available La enfermedad renal crónica (ERC es un importante problema de salud pública que puede afectar en sus diferentes estadios a cerca del 10% de la población española y que supone una elevada morbimortalidad, así como un importante consumo de recursos al Sistema Nacional de Salud. Diez sociedades científicas involucradas en el manejo del paciente renal nos hemos puesto de acuerdo para hacer una puesta al día del anterior documento de consenso sobre ERC de 2007. El presente es la edición abreviada del documento general extenso, que puede ser consultado en las páginas Web de cada una de las sociedades firmantes. Contiene los siguientes aspectos: definición, epidemiología y factores de riesgo de la ERC; criterios de diagnóstico, evaluación y estadificación de la ERC, albuminuria y estimación del filtrado glomerular; concepto y factores de progresión; criterios de derivación a nefrología; seguimiento del paciente, actitudes y objetivos por especialidad; prevención de la nefrotoxicidad; detección del daño cardiovascular; actitudes, estilo de vida y tratamiento: manejo de la hipertensión arterial, dislipidemia, hiperglucemia, tabaquismo, obesidad, hiperuricemia, anemia, alteraciones del metabolismo mineral y óseo; seguimiento coordinado por atención primaria-otras especialidades-nefrología; manejo del paciente en tratamiento renal sustitutivo, hemodiálisis, diálisis peritoneal y trasplante renal; tratamiento paliativo de la uremia terminal. Esperamos que sirva de gran ayuda en el manejo multidisciplinar del paciente con ERC, a la vista de las recomendaciones más actualizadas.

  14. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

    Science.gov (United States)

    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome. PMID:26398482

  15. Linagliptin Limits High Glucose Induced Conversion of Latent to Active TGFß through Interaction with CIM6PR and Limits Renal Tubulointerstitial Fibronectin.

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    Muralikrishna Gangadharan Komala

    Full Text Available In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4 inhibitors have been shown to be antifibrotic. We have previously shown that cation independent mannose-6-phosphate receptor (CIM6PR facilitates the conversion of latent to active transforming growth factor β1 (GFß1 in renal proximal tubular cells (PTCs and linagliptin (a DPP4 inhibitor reduced this conversion with downstream reduction in fibronectin transcription.We wanted to demonstrate that linagliptin reduces high glucose induced interaction between membrane bound DPP4 and CIM6PR in vitro and demonstrate reduction in active TGFß mediated downstream effects in a rodent model of type 1 diabetic nephropathy independent of high glycaemic levels.We used human kidney 2 (HK2 cells and endothelial nitric oxide synthase knock out mice to explore the mechanism and antifibrotic potential of linagliptin independent of glucose lowering. Using a proximity ligation assay, we show that CIM6PR and DPP4 interaction was increased by high glucose and reduced by linagliptin and excess mannose-6-phosphate (M6P confirming that linagliptin is operating through an M6P-dependent mechanism. In vivo studies confirmed these TGFß1 pathway related changes and showed reduced fibronectin, phosphorylated smad2 and phosphorylated smad2/3 (pSmad2/3 with an associated trend towards reduction in tubular atrophy, which was independent of glucose lowering. No reduction in albuminuria, glomerulosclerotic index or cortical collagen deposition was observed.Linagliptin inhibits activation of TGFß1 through a M6P dependent mechanism. However this in isolation is not sufficient to reverse the multifactorial nature of diabetic nephropathy.

  16. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  17. A new mouse model to explore therapies for preeclampsia.

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    Abdulwahab Ahmed

    Full Text Available BACKGROUND: Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE. DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF signaling by soluble VEGF receptor 1 (sFlt-1 is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. CONCLUSIONS/SIGNIFICANCE: We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

  18. Albumin contributes to kidney disease progression in Alport syndrome.

    Science.gov (United States)

    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

  19. Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1α in db/db mice.

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    Yu Ah Hong

    Full Text Available Peroxisome proliferator-activated receptor (PPAR-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK, and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α-estrogen-related receptor (ERR-1α-phosphorylated acetyl-CoA carboxylase (pACC, and suppression of sterol regulatory element-binding protein (SREBP-1 and carbohydrate regulatory element-binding protein (ChREBP-1, key downstream effectors of lipid metabolism. Fenofibrate decreased the activity of phosphatidylinositol-3 kinase (PI3K-Akt phosphorylation and FoxO3a phosphorylation in kidneys, increasing the B cell leukaemia/lymphoma 2 (BCL-2/BCL-2-associated X protein (BAX ratio and superoxide dismutase (SOD 1 levels. Consequently, fenofibrate recovered from renal apoptosis and oxidative stress, as reflected by 24 hr urinary 8-isoprostane. In cultured mesangial cells, fenofibrate prevented high glucose-induced apoptosis and oxidative stress through phosphorylation of AMPK, activation of PGC-1α-ERR-1α, and suppression of SREBP-1 and ChREBP-1. Our results suggest that fenofibrate improves lipotoxicity via activation of AMPK-PGC-1α-ERR-1α-FoxO3a signaling, showing its potential as a therapeutic modality for diabetic nephropathy.

  20. Assessing Framingham cardiovascular risk scores in subjects with diabetes and their correlation with diabetic retinopathy

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    Deepali R Damkondwar

    2012-01-01

    Full Text Available Aim: To study the Framingham cardiovascular risk assessment scores in subjects with diabetes and their association with diabetic retinopathy in subjects with diabetes. Materials and Methods: In this population-based prospective study, subjects with diabetes were recruited (n=1248; age ≥40 years. The Framingham cardiovascular risk scores were calculated for 1248 subjects with type 2 diabetes. The scores were classified as high risk (>10%, and low risk (<10%. Results: Out of the 1248 subjects, 830 (66.5% patients had a low risk of developing cardiovascular disease (CVD in 10 years and 418 (33.5% had a high risk of developing CVD in 10 years. The risk of developing CVD was more in males than females (56.8% vs. 7% The prevalence of both diabetic retinopathy and sight-threatening retinopathy was more in the high-risk group (21% and 4.5%, respectively. The risk factors for developing diabetic retinopathy were similar in both the groups (low vs. high - duration of diabetes (OR 1.14 vs. 1.08, higher HbA1c (OR 1.24 vs. 1.22, presence of macro- and microalbuminuria (OR 10.17 vs. 6.12 for macro-albuminuria and use of insulin (OR 2.06 vs. 4.38. The additional risk factors in the high-risk group were presence of anemia (OR 2.65 and higher serum high density lipoprotein (HDL cholesterol (OR 1.05. Conclusion: Framingham risk scoring, a global risk assessment tool to predict the 10-year risk of developing CVD, can also predict the occurrence and type of diabetic retinopathy. Those patients with high CVD scores should be followed up more frequently and treated adequately. This also warrants good interaction between the treating physician/cardiologist and the ophthalmologist.

  1. Neonatal hypertension – a long-term pilot follow-up study

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    Chaudhari T

    2013-06-01

    Full Text Available Tejasvi Chaudhari,1 Michael C Falk,2,3 Rajeev Jyoti,2,4 Susan Arney,5 Wendy Burton,5 Alison L Kent1,2 1Department of Neonatology, Canberra Hospital, Woden, ACT, Australia; 2Australian National University Medical School, Canberra, ACT, Australia; 3Department of Nephrology, 4Medical Imaging Department, 5Centre for Newborn Care, Canberra Hospital, Woden, ACT, Australia Background: Neonatal hypertension occurs in up to 3% of neonates, more commonly in those admitted to neonatal intensive care. The aims of this study were to review renal function and renal volumes in children who had a history of neonatal hypertension. Methods: Children with a history of neonatal hypertension from January 2001 to December 2008 were included in the study during 2011. Blood pressure, weight, height, and body mass index were recorded. Renal ultrasound with 3D volume, urine for electrolytes, albumin, ß2 microglobulin, and blood for electrolytes, urea, creatinine, calcium, phosphate, renin, and aldosterone were collected depending on parental consent. Results: Of the 41 neonates with neonatal hypertension, eleven (27% were included in the study (six died; 24 moved interstate or declined involvement. One child (9% was still on antihypertensive medication and one was found to be hypertensive on review. This child had small volume kidneys and albuminuria. Three out of nine renal volume measurements were low (33% and two out of eleven had renal scarring (18%. The six available renin/aldosterone results were normal. Conclusion: This study suggests there are long-term renal and blood pressure implications for neonates with hypertension and ongoing surveillance of blood pressure and renal function should be performed throughout childhood and into early adulthood. Keywords: neonate, hypertension, renal ultrasound, 3D

  2. Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment

    International Nuclear Information System (INIS)

    Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m2) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie–Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response

  3. 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. PMID:26831938

  4. High prevalence of chronic kidney disease in a semi-urban population of Western India

    Science.gov (United States)

    Trivedi, Hargovind; Vanikar, Aruna; Patel, Himanshu; Kanodia, Kamal; Kute, Vivek; Nigam, Lovelesh; Suthar, Kamlesh; Thakkar, Umang; Sutariya, Harsh; Gandhi, Shruti

    2016-01-01

    Background Globally there is an increase in incidence of chronic kidney diseases (CKDs). Diabetes mellitus (DM), hypertension and stone diseases are the major risk factors for CKD. We organized kidney disease screening camps in a semi-urban population of Gujarat, India on the occasion of World Kidney Day (WKD). Methods Voluntary participants from six towns were screened. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and CKD was defined as an eGFR <60 mL/min/1.73 m2 or albuminuria ≥1+. Urogenital ultrasonography was performed with emphasis on stone burden. Participants with known diabetes, stone diseases, hypertension, kidney/liver/cardiac disease, hepatitis, HIV, transplant recipients, pregnant women and those <18 years were excluded from the study. Results Of the 2350 participants (1438 men), CKD was found in 20.93% and eGFR <60 mL/min/1.73 m2 was noted in 8.29% of participants. The prevalence of CKD peaked after the seventh decade of life in both genders. There was no significant difference in the prevalence of CKD between coastal and non-coastal regions, however, obesity, hypertension and diabetes were more common in the coastal belt, whereas stone burden was greater in the non-coastal region. Conclusions The prevalence of CKD in a semi-urban apparently healthy Indian population was higher than the reported prevalence in developed countries. Significant differences between regions point to the need to evaluate and correctregion-specific risk factors. PMID:27274831

  5. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

    Science.gov (United States)

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents. PMID:27431456

  6. Epidemiologic investigation of chronic kidney disease in Chengdu urban population%成都市城市人群慢性肾脏病流行病学调查

    Institute of Scientific and Technical Information of China (English)

    郭宗琳; 付平; 王启容; 周雅南; 梁江红; 董俊邑; 付彬; 杨福华; 卢小琼; 苏晓渝

    2012-01-01

    ,blood creatinine,uromicroprotein/creatinine ratio,routine urine examination,etc) were measured.The prevalence and risk factors of CKD in Chengdu urban population and the prevalence of CKD in risk population were elucidated.Results Eligible data of 5326 subjects were enrolled in the study.After the adjustment of age and gender component,the prevalence of albuminuria was 11.54%,reduced eGFR was 5.54%,hematuria was 3.87%,and CKD was 18.32%; the recognition was 1.93%.In addition,the prevalence of albuminuria was respectively 23.79%,28.00%,14.08%; prevalence of reduced eGFR was respectively 4.76%,4.53%,3.26%; prevalence of hematuria was respectively 2.94%,3.20%,2.37% in 3098 people with hypertension,diabetes or hyperlipaemia.Independent risk factors of albuminuria were female,hypertension,diabetes,hyperlipemia and high BMI.Independent risk factors of reduced eGFR were female,age,hyperuricemia and hypertension.Drink was negatively correlated with reduced eGFR.Independent risk factors of hematuria were female and age.Conclusions The prevalence of CKD is quite high and the recognition rate is low in the Chengdu urban populaton.Risk factors of CKD are age,female,diabetes,hypertension,hyperlipemia,hyperuricemia and high BMI.Control of the development of metabolic disease can reduce the CKD.

  7. Changes of urinary L-FABP, KIM-1, NGAL and serum cystatin C in diabetic nephropathy and its clinical value%尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    梁雅灵; 杨茂君; 李衍辉; 黎秋晗; 黄炜; 徐勇

    2016-01-01

    Objective To investigate the changes of urinary liver-type fatty acid binding protein (L-FABP),kidney injury molecule-1 (KIM-1),neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C in diabetic nephropathy and its clinical value.Methods A total of 118 patients diagnosed with type 2 diabetes in the Department of Endocrinology of Affiliated Hospital of Sichuan Medical University from October 2011 to October 2012 were recruited in this study.According to their urinary albumin-to-creatinine ratio(UACR),patients were divided into normal albuminuria group(n =45),microalbuminuria group (n =42),and macroalbuminuria group (n =43).A total of 41 healthy subjects were enrolled as normal control group(n =41).Enzyme-linked immunosorbent assays were used to measure the levels of urinary L-FABP,KIM-1 and NGAL.Turbidimetric inhibition immuno-assay was used to measure the expression of serum cystatin C.All the urinary indicators were adjusted by the level of urine creatinine.Changes of biomarkers in each group and their crrelations between UACR,eGFR were also compared.Results Compared with normal control group,urinary L-FABP and serum cystatin C were significantly increased in diabetic groups (x2 =77.959,104.003,all P < 0.05);urinary KIM-1 was also significantly increased (x2 =29.711,P < 0.05).Urinary NGAL was increased in microalbuminuria group and macroalbuminuria group compared with normal control group and normal albuminuria group(x2 =23.833,P < 0.05),but there were no significant difference between normal albuminuria group and normal control group.Urinary L-FABP,KIM-1,NGAL and serum cystatin C were positively correlated with UACR (r =0.719,0.427,0.327,0.726,all P < 0.01);while L-FABP and serum cystatin C were negatively correlated with eGFR (r =-0.301,-0.791,all P < 0.01).Conclusion Urinary L-FABP,KIM-1,NGAL and serum cystatin C are increased in early diabetic nephropathy,while urinary L-FABP and serum cystatin C may be the better biomarkers to

  8. 上海城市社区成年人群慢性肾脏病流行病学研究%Community-based study on adult chronic kidney diseases and its associated risk factors in Shanghai

    Institute of Scientific and Technical Information of China (English)

    黄燕萍; 樊绮诗; 陈楠; 王伟铭; 裴道灵; 沈平雁; 俞海瑾; 史浩; 章倩莹; 徐静; 吕轶伦

    2008-01-01

    Objective To investigate the prevalence, awareness and risk factors of chronic kidney disease (CKD) among community adult population in Shanghai, China, in order to provide early diagnosis and treatment of CKD, and informations for national health policy makers.Methods Two thousand five hundred and ninety six residents (≥ 18 years old) were randomly selected from community population in Changning district of Shanghai, China. They were interviewed and tested for albuminuria -morning spot urine albumin to creatinine ratio [ACR, abnormal: ≥ 17 mg/g (male), ≥25 mg/g (female)], reduced renal function-estimated GFR by abbreviated MDRD equation [abnormal: <60 ml ·rain-1 (1.73 m2)-1] and hematuria-morning spot urine dipstick confirmed by urine microscopy. The associations among demographic characteristics, healthy characteristics (e.g. diabetes and hypertension) and indicators of kidney damage were examined. The investigators and neighborhood committee were well trained. Those who had semiquantitative positive were detected again by albuminuria-morniag spot urine albumin to creatinine ratio after three months. Results Two thousand five hundred and fifty four residents with complete data were enrolled in the study. Albuminuria was detected in 6.3% of subjects, reduced renal function in 5.8%, hematuria in 1.2%. Approximately 11.8% of these subjects had at least one indicator of kidney damage. The awareness rate of CKD was 8.2%. The Logistic regression model showed that hyperuricemia, nephrolithiasis, anemia, diabetes, central obesity, hypertension and age contributed to the development of CKD. Conclusions The prevalence of CKD in community adult population in Shanghai is 11.8%, And the awareness rate of CKD is 8.2%. Hyperuricemia, nephrolithiasis, anemia, diabetes, central obesity, hypertension and age are risk factors of CKD.%目的 获取上海城市社区成年人群慢性肾脏病流行病学及其高危人群数据,有助于慢性肾脏病的早期发现、早

  9. 老年代谢综合征患者静息心率增加与靶器官损害的相关性%Study on the relationship between the resting heart rate and target organ damage in elderly patients with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    丁向东; 刘平; 魏国; 刘雅斐; 倪一虹

    2008-01-01

    Objective To investigate the relationship between the resting heart rate (RHR) and target organ damage (TOD) in elderly patients with metabolic syndrome(MS). Methods 264 elderly patients with MS were divided into four groups according to the level of RHR: RHR1 group, RHR<65 beats/minute (bpm) (46 cases) ;RHR2 group, 65≤RHR<75 bpm (77 cases);RHR3 group, 75 bpm≤RHR<85 bpm (89 cases);RHR4 group, RHR≥85 bpm (52 cases).Electrocardiography, echocardiography, carotid uhrasonography, crcatinine clearance rate (Ccr) and quantitative assay of 24 hours' albuminuria were performed. Results (1) Compared with RHR1, RHR2 and RHR3 groups, RHR4 group showed higher levels of carotid intima-medial thickness (IMT), carotid arterial diameter (CAD), left ventricular mass index (LVMI) and albuminuria(P< 0.05 or P<0.01), and lower levels of left ventricular ejection fraction (LVEF) and Ccr (all P< 0.01). (2) The IMT, CAD, LVMI and albuminuria were positively correlated with RHR (r=0.33, 0.23, 0.61, 0.58, respectively, all P<0.01). However, the LVEF and Ccr were negatively correlated with RHR (r=-0.59, -0.51, all P<0.01). (3) Logistic multivariate analysis showed that RHR and pulse pressure (PP) had effects on myocardial hypertrophy, coronary heart disease, heart failure, cerebral stroke and renal dysfunction(P<0.05 or P<0.01). Except heart failure, PP played a more important role than RHR. Coneinsions RHR may be an independent risk factors for TOD in elderly patients with MS,and RHR regulation is important for the development of MS in the elderly.%目的 探讨老年代谢综合征患者静息心率(RHR)与靶器官损害的关系. 方法 入选老年代谢综合征患者264例,按RHR水平分为4组:RHRl组;RHR<65次/min 46例;RHR2组:65次/min≤RHR<75次/min 77例;RHR3组:75次/min≤RHR<85次/min 89例;RHR4组:RHR≥85次/min 52例.对入选患者检查心电图、超声心动图、颈动脉超声、肌酐清除率(Ccr)及尿微量白蛋白. 结果 (1)RHR4组的颈动脉内膜

  10. [Nowe Miasto on the Pilica rier--the first XIXth Physiotherapeutic Institution in Polish Kingdom].

    Science.gov (United States)

    Kozera, Justyna Małgorzata

    2005-01-01

    The first nineteenth- century clinic of natural medicine in Poland was founded in 1874 in Nowe Miasto on the Pilica. The founder was Doctor Jan Kapistran Bieliński. The clinic being located by the riverside was fed with 5 springs of cold water and was surrounded by a big park. In the clinic following treatments were provided: hydrotherapy (a hot, cool, steam, salt, gas, aromatic bath, showers) kinesthesiotherapy (treatment by motion, gymnastics), electrotherapy (static electricity, electric bathing), massage and dietary and pharmacological treatment. In Nowe Miasto diseases of the nervous system (spinal neurasthenia, epilepsy, chorea, nervous palsy) were treated as well as of the vascular system (haemorrhage, anaemia, cardiovascular disorder), the respiratory system (bronchitis, pneumoitis, asthma), the digestive system (catarrh and ulceration of stomach and intestines), the sexual system (disorders of menstruation, infertility), urinary tracts (the atonia of bladder, albuminuria, glycosuria) and others (rheumatism, obesity, deafness, convalescence). The clinic had a good reputation and was still being extended. In 1896 it consisted of 26 buildings which housed 150 guest rooms. A very modern medicine department "Marylin" rated the clinic of Nowe Miasto among the top European clinics. The Bieliński's clinic employed following staff: 5 doctors, 2 paramedics, 10 male baths attendants (male nurses who worked in baths), 7 female baths attendants and between ten and twenty support staff. The clinic was open the whole year treating about 400 persons yearly. The patients came from the whole area of Congress Kingdom of Poland as well as from cities abroad: Moscow, St Petersburg, Smolensk, Cracow, London or New York. The majority of patients came from Lódź and Warsaw. The Doctor J.K. Bielinski's clinic was a cultural centre, too. In their spare time the clients of the clinic were offered trips, balls, lectures, stage performances, concerts and painting exhibitions. I

  11. Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients

    Science.gov (United States)

    Delić, Denis; Eisele, Claudia; Schmid, Ramona; Baum, Patrick; Wiech, Franziska; Gerl, Martin; Zimdahl, Heike; Pullen, Steven S.; Urquhart, Richard

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies. PMID:26930277

  12. Role of inflammation in diabetic nephropathy%炎性反应与糖尿病肾病

    Institute of Scientific and Technical Information of China (English)

    张红; 章向成; 朱大龙

    2015-01-01

    传统观点认为,代谢异常及血流动力学障碍是糖尿病肾病的主要原因.近来研究认为,天然免疫介导的慢性、低水平炎性反应在糖尿病肾病的发生及发展中起核心作用.细胞黏附分子、生长因子、趋化因子和促炎细胞因子在糖尿病患者肾组织的表达增多,且血清和尿中的细胞因子和黏附分子的水平与白蛋白尿相关.研究发现一些抗炎药物在糖尿病动物模型中有肾保护作用.因此深入了解糖尿病肾病的发病机制,并转化到临床开发相应的治疗策略,将可延缓甚至阻止糖尿病肾病的发生和发展.%Traditional opinions suggest that metabolic disorder and hemodynamic alterations are the critical causes of diabetic nephropathy.However,recent studies indicate that a chronic low-grade inflammation and an activation of the immune system are involved in development and progression of diabetic nephropathy.Expression of cell adhesion molecules,growth factors,chemokines and pro-inflammatory cytokines are increased in renal tissues of diabetic patients,and serum,urinary cytokines and cell adhesion molecules correlate with albuminuria.Several kinds of drugs that have anti-inflammatory actions show renal protective effects in diabetic animals.Therefore,investigating the role of inflammation in the development of diabetic nephropathy and translating it into new therapeutic strategies may be helpful in the prevention and treatment of diabetic nephropathy.

  13. Effect of a Long-Term Behavioral Weight Loss Intervention on Nephropathy in Overweight or Obese Adults with Type 2 Diabetes: the Look AHEAD Randomized Clinical Trial

    Science.gov (United States)

    Knowler, William C.; Bahnson, Judy L.; Bantle, John P.; Bertoni, Alain G.; Bray, George A.; Chen, Haiying; Cheskin, Lawrence; Clark, Jeanne M.; Egan, Caitlin; Evans, Mary; Foreyt, John P.; Glasser, Stephen P.; Greenway, Frank L.; Gregg, Edward W.; Hazuda, Helen P.; Hill, James O.; Horton, Edward S.; Hubbard, Van S.; Jakicic, John M.; Jeffery, Robert W.; Johnson, Karen C.; Kahn, Steven E.; Kitabchi, Abbas E.; Korytkowski, Mary; Krakoff, Jonathan; Kure, Anne; Lewis, Cora E.; Maschak-Carey, Barbara J.; Michaels, Sara; Montez, Maria G.; Nathan, David M.; Nyenwe, Ebenezer; Patricio, Jennifer; Peters, Anne; Pi-Sunyer, Xavier; Pownall, Henry; Wadden, Thomas A.; Wagenknecht, Lynne E.; Williamson, David F.; Wing, Rena R.; Wyatt, Holly; Yanovski, Susan Z.

    2015-01-01

    Background Long-term effects of behavioral weight loss interventions on diabetes complications are unknown. We assessed whether an intensive lifestyle intervention (ILI) affects the development of nephropathy in Look AHEAD, a multicenter randomized clinical trial in type 2 diabetes. Methods 5145 overweight or obese persons aged 45–76 years with type 2 diabetes were randomized to ILI designed to achieve and maintain weight loss through reduced caloric consumption and increased physical activity or to a diabetes support and education (DSE) group. Randomization to ILI or DSE, in a 1:1 ratio, was implemented in a central web-based data management system, stratified by clinical center, and blocked with random block sizes. Outcomes assessors and laboratory staff were masked to treatment. The interventions ended early because of lack of effect on the primary outcome of cardiovascular disease events. Albuminuria and estimated glomerular filtration rate were prespecified “other” outcomes and were assessed from baseline through 9.6 years (median) of follow-up until the interventions ended. They were combined post-hoc to define the main outcome for this report: very-high-risk chronic kidney disease (CKD) based on the 2013 Kidney Disease Improving Global Outcomes classification. Data were analyzed by intention to treat. The trial is registered as Clinicaltrials.gov NCT00017953. Findings The incidence rate of very-high-risk CKD was 31% lower in ILI than DSE with hazard rates of 0.90 cases/100 person-years in DSE and 0.63 in ILI (difference=0.27 cases/100 person-years, hazard ratio and 95% confidence interval: HR=0.69, 0.55 to 0.87). This effect was partly attributable to reductions in weight, HbA1c, and blood pressure. Interpretation Weight loss should be considered as an adjunct to medical therapies to prevent or delay progression of CKD in overweight or obese persons with type 2 diabetes. Primary Funding National Institute of Diabetes and Digestive and Kidney Diseases

  14. Compromiso renal en pacientes HIV+

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    María Marta Pernasetti

    2010-06-01

    Full Text Available Varias complicaciones nefrológicas pueden ocurrir durante la infección por el virus de la inmunodeficiencia humana (HIV especialmente en estadios avanzados de la enfermedad o relacionadas con otras infecciones o drogas. Poco conocida es la prevalencia de alteraciones renales subclínicas de pacientes HIV+ surgidas como complicación o relacionadas a la infección y/o tratamiento. Realizamos un corte transversal de pacientes asintomáticos HIV+ referidos en forma consecutiva al consultorio de nefrología para la detección de alteraciones nefrológicas. Se estudiaron 52 pacientes adultos mediante exámenes de sangre y orina, ultrasonido y biopsia renal. Edad media 39.9 ± 10.6 años, 88% varones, tiempo de diagnóstico de la infección: 53.2 ± 41.2 (2-127 meses. El 71% tenían síndrome de inmunodeficiencia adquirida (HIV-sida y el 77% recibían con antirretrovirales. La carga viral al momento del estudio fue 7043 ± 3322 copias y el recuento de CD4+ 484 ± 39 cel/mm³. El 30.7% presentó alteraciones del sedimento urinario: albuminuria: 16.6%, hematuria microscópica: 11.5%, hipercalciuria: 10.8% y cristaluria 6%. La media del filtrado glomerular fue 102.2 ± 22.9 ml/min (rango: 34-149. El 41% presentó anormalidades que corresponderían a enfermedad renal crónica (estadios 1 a 3. Los pacientes con alteraciones tenían mayor edad, con duración más prolongada de la infección. Las anomalías renales no se asociaron con mayor prevalencia de HIV-sida. Dos pacientes fueron biopsiados, con hallazgos de nefritis túbulo-intersticial crónica con cristales y glomerulonefritis por IgA. No hubo hallazgos de nefropatía por HIV. El amplio espectro y la alta prevalencia de anormalidades nefrológicas subclínicas encontradas sugieren que los pacientes asintomáticos HIV+ deberían realizar evaluaciones nefrológicas de rutina.

  15. Moderate antiproteinuric effect of add-on aldosterone blockade with eplerenone in non-diabetic chronic kidney disease. A randomized cross-over study.

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    Lene Boesby

    Full Text Available BACKGROUND: Reduction of proteinuria and blood pressure (BP with blockers of the renin-angiotensin system (RAS impairs the progression of chronic kidney disease (CKD. The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD. STUDY DESIGN: Open randomized cross-over trial. SETTING AND PARTICIPANTS: Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours. INTERVENTION: Eight weeks of once-daily administration of add-on 25-50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade. OUTCOMES & MEASUREMENTS: 24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance. RESULTS: The mean urinary albumin excretion was 22% [CI: 14,28], P < 0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p-potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia. LIMITATIONS: Open label, no wash-out period and a moderate sample size. CONCLUSIONS: In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium. TRIAL REGISTRATION: Clinicaltrials.gov NCT00430924.

  16. ORIGINAL ARTIC LE: LEUCOCYTOCLASTIC VASCULITIS: A CLINICOPATHOLOGICAL STUDY

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    Anila Sunandini

    2015-10-01

    Full Text Available Vasculitis is the inflammation of blood vessels weather it can be arteries , veins or both. In CSVV , the vasculitic process involves just the small blood vessels within the skin , primarily postcapillary venules. The etiology and clinical features are varied but histopathology is characterized by leucocytoclasia. AIMS AND OBJECTIVES : The present study was done to know t h e spectrum of variou s cutaneous manifestations and etiology of leucocytoclastic vasculitis. MATERIALS AND METHODS : The study was carried out on patients who were clinically diagnosed as cutaneous vasculitis , attending the outpatient department of dermatol ogy , venereology and leprosy , K ing George hospital , affiliated to Andhra medical college , Visakhapatnam from January 2013 to December 2013. It is a cross - sectional type of study and a total of 20 cases were studied. INCLUSION CRITERIA : All patients attendi ng to opd , clinically diagnosed as cutaneous vasculitis irrespective of age and sex were included in study. EXCLUSION CRITERIA : Patients with thrombocytopenic purpura , disorders of coagulation and on warfarin/heparin treatment . RESULTS : Out of 20 patients enrolled in study , most common age group is in between 20 - 40 years , female preponderance , and most of patients , 75% presented acutely with lesions less than 6 weeks duration , 70% of patients had symptoms of burning and itching in lesions , 40% had history of low grade fever , 45% had arthralgias , 50% had gastrointestinal symptoms , 20% had history of sore throat , 10% had history of significant drug exposure within 6 weeks of onset of lesions. Majority of patients had elevated ESR (75%. 25% of patients had AS O titres positive , of which only 15% has throat swab positive for beta - hemolytic streptococci , ANA titres were positive in 5% , renal involvement in the form of albuminuria was seen in 20% , hematuria in 10% , urinary tract infection in 10% of cases , histopat hology of all patients showed

  17. The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension.

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    Weiss, Sebastian; Rosendahl, Alva; Czesla, Daniel; Meyer-Schwesinger, Catherine; Stahl, Rolf A K; Ehmke, Heimo; Kurts, Christian; Zipfel, Peter F; Köhl, Jörg; Wenzel, Ulrich O

    2016-06-01

    Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here, we determined the role of anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this purpose, we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in ANG II-induced renal and cardiac injury. Expression of C5aR1 on infiltrating and resident renal as well as cardiac cells was determined using a green fluorescent protein (GFP)-C5aR1 reporter knockin mouse. Flow cytometric analysis of leukocytes isolated from the kidney of GFP-C5aR1 reporter mice showed that 28% of CD45-positive cells expressed C5aR1. Dendritic cells were identified as the major C5aR1-expressing population (88.5%) followed by macrophages and neutrophils. Using confocal microscopy, we detected C5aR1 in the kidney mainly on infiltrating cells. In the heart, only infiltrating cells stained C5aR1 positive. To evaluate the role of C5aR1 deficiency in hypertensive injury, an aggravated model of hypertension was used. Unilateral nephrectomy was performed followed by infusion of ANG II (1.5 ng·g(-1)·min(-1)) and salt in wild-type (n = 34) and C5aR1-deficient mice (n = 32). C5aR1-deficient mice exhibited less renal injury, as evidenced by significantly reduced albuminuria. In contrast, cardiac injury was accelerated with significantly increased cardiac fibrosis and heart weight in C5aR1-deficient mice after ANG II infusion. No effect was found on blood pressure. In summary, the C5a:C5aR1 axis drives end-organ damage in the kidney but protects from the development of cardiac fibrosis and hypertrophy in experimental ANG II-induced hypertension. PMID:27053686

  18. L-citrulline protects from kidney damage in type 1 diabetic mice.

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    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  19. Id proteins regulate capillary repair and perivascular cell proliferation following ischemia-reperfusion injury.

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    David Lee

    Full Text Available Acute kidney injury (AKI results in microvascular damage that if not normally repaired, may lead to fibrosis. The Id1 and 3 proteins have a critical role in promoting angiogenesis during development, tumor growth and wound repair by functioning as dominant negative regulators of bHLH transcription factors. The goal of this study was to determine if Id proteins regulate microvascular repair and remodeling and if increased Id1 expression results in decreased capillary loss following AKI. The effect of changes in Id expression in vivo was examined using Id1-/-, Id3RFP/+ (Id1/Id3 KO and Tek (Tie2-rtTA, TRE-lacz/TRE Id1 (TRE Id1 mice with doxycycline inducible endothelial Id1 and β-galactosidase expression. Id1 and 3 were co-localized in endothelial cells in normal adult kidneys and protein levels were increased at day 3 following ischemia-reperfusion injury (IRI and contralateral nephrectomy. Id1/Id3 KO mice had decreased baseline capillary density and pericyte coverage and increased tubular damage following IRI but decreased interstitial cell proliferation and fibrosis compared with WT littermates. No compensatory increase in kidney size occurred in KO mice resulting in increased creatinine compared with WT and TRE Id1 mice. TRE Id1 mice had no capillary rarefaction within 1 week following IRI in comparison with WT littermates. TRE Id1 mice had increased proliferation of PDGFRβ positive interstitial cells and medullary collagen deposition and developed capillary rarefaction and albuminuria at later time points. These differences were associated with increased Angiopoietin 1 (Ang1 and decreased Ang2 expression in TRE Id1 mice. Examination of gene expression in microvascular cells isolated from WT, Id1/Id3 KO and TRE Id1 mice showed increased Ang1 and αSMA in Id1 overexpressing cells and decreased pericyte markers in cells from KO mice. These results suggest that increased Id levels following AKI result in microvascular remodeling associated with

  20. Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

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    Bin Yi

    Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

  1. Diabetic Kidney Disease and Hypertension: A True Love Story

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    Verma, Anand; Vyas, Sony; Agarwal, Abhishek; Abbas, Shahid; Agarwal, Devi Prasad

    2016-01-01

    Introduction Diabetes Mellitus (DM) remains one of the commonest causes of structural and functional kidney abnormalities leading to End Stage Renal Disease (ESRD). The next most common cause is hypertension. It is utmost important to investigate the association between diabetic nephropathy and hypertension because it is a major causal factor of end-stage kidney failure in Type 2 Diabetes Mellitus (T2DM). Aim The aim of the present study was to investigate the association between albuminuria, hypertension and estimated glomerular filtration rate (eGFR) in a prospective cohort of T2DM patients in a developing country. Materials and Methods A total of 824 patients were enrolled from a tertiary healthcare center in central India. This study was performed in three groups: normal controls (232), type 2 diabetics without nephropathy (185) and type 2 diabetics with nephropathy (407). Diabetic nephropathy was clinically defined by the presence of persistent proteinuria of > 500mg/day in a diabetic patient in the absence of clinical or laboratory evidence of other kidney or urinary tract disease. Hypertension was categorized based on JNC 7 classification. Detailed clinical history was obtained from all subjects. Student’s t-test was applied to see the difference in mean values of quantitative data in two groups. Chi-Square test was applied to see the difference in frequency of discrete variables in two groups. Results A 66.3% diabetic nephropathy patients and 51.9% type 2 diabetics without nephropathy were found hypertensive in present study; In contrast only 14.7% controls had hypertension. No association of hypertension was found with age and gender in either group. Serum creatinine and eGFR was found significantly different in hypertensive diabetic nephropathy patients than normotensive (p=0.002 and <0.0001 respectively). Conclusion Our study found that hypertension was an independent risk factor for the Diabetic Kidney Disease (DKD). Along with this, a proportional

  2. Prevalence & Risk Factors of Nephropathy in Type 2 Diabetic Patients

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    Vimalkumar V K

    2011-08-01

    Full Text Available Background: 31.7 million people in India are suffering from diabetes. Diabetic nephropathy (Kimmelstiel-Wilson syndrome is the leading cause of end-stage renal disease (ESRD worldwide and a leading cause of DM-related morbidity and mortality. It is estimated that 79.4 million diabetic patients will be in India by 2030. So a study was done on the prevalence rate of diabetic nephropathy (DN and its associated risk factors.Aims and Objectives: This study is a small cross sectional study conducted in a tertiary hospital (Dr. Ambedkar institute of diabetes, Kilpauk medical college hospital, Chennai.. The objective is to analyze the prevalence of DN and to determine the factors leading to DN in type 2 diabetic patients (mainly containing urban Asian Indian populationMaterials and Methods: 200 Type 2 diabetic patients were randomly selected. All the patients were interviewed with a questionnaire. A detailed history including risk factors like age ,sex , socio economic status, duration of diabetes , smoking , alcohol , family history of DM and kidney disease, Ischemic heart disease(IHD, Oral Hypoglycemic Drugs(OHA , Insulin was taken followed by measurement of blood pressure, BMI assessment, urine analysis for albuminuria and microalbuminuria using dipsticks, lipid profile, GFR estimation, retinopathy screening. Statistical analysis was done by SPSS software. Univariate analysis, Chi-square and Binary Logistic Regression Model was used.Results: In this study prevalence rate of overt nephropathy is 2.5% and microalbuminuria is 13%, Using Binary logistic regression analysis, Woman gender, Duration of diabetes, family history of kidney disease, Hypertension, BMI, GFR, retinopathy were found to be significantly associated with overt DN. There was no increased risk among IHD patients, smokers, alcoholics and no significant relationship with treatment history.Limitations: This is a hospital based cross sectional study. Population based Case control studies

  3. Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan

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    Chien, Hung-Yu; Chen, Chang-Yi; Chiu, Yen-Hui; Lin, Yi-Chun; Li, Wan-Chun

    2016-01-01

    Objectives: Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. Methods: A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR300mg/g; N=21) as well as 18 low-eGFR (eGFR60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. Results: The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. Conclusion: Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.

  4. Association of urinary injury biomarkers with mortality and cardiovascular events.

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    Sarnak, Mark J; Katz, Ronit; Newman, Anne; Harris, Tamara; Peralta, Carmen A; Devarajan, Prasad; Bennett, Michael R; Fried, Linda; Ix, Joachim H; Satterfield, Suzanne; Simonsick, Eleanor M; Parikh, Chirag R; Shlipak, Michael G

    2014-07-01

    Kidney damage is a common sequela of several chronic pathologic conditions. Whether biomarkers of kidney damage are prognostic for more severe outcomes is unknown. We measured three urinary biomarkers (kidney injury molecule-1 [KIM-1], IL-18, and albumin) in 3010 individuals enrolled in the Health, Aging and Body Composition (Health ABC) study and used Cox proportional hazards models to investigate the associations of urinary KIM-1/creatinine (cr), IL-18/cr, and albumin/cr (ACR) with all-cause mortality and cardiovascular disease (CVD). Multivariable models adjusted for demographics, traditional CVD risk factors, and eGFR. Mean age of participants was 74 years, 49% of participants were men, and 41% of participants were black. During the median 12.4 years of follow-up, 1450 deaths and 797 CVD outcomes occurred. Compared with the lowest quartile, successive quartiles had the following adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) for mortality: KIM-1/cr: (1.21; 1.03 to 1.41), (1.13; 0.96 to 1.34), and (1.28; 1.08 to 1.52); IL-18/cr: (1.02; 0.88 to 1.19), (1.16; 0.99 to 1.35), and (1.06; 0.90 to 1.25); ACR: (1.08; 0.91 to 1.27), (1.24; 1.06 to 1.46), and (1.63; 1.39 to 1.91). In similar analyses, only ACR quartiles associated with CVD: (1.19; 0.95 to 1.48), (1.35; 1.08 to 1.67), and (1.54; 1.24 to 1.91). Urinary KIM-1 had a modest association with all-cause mortality but did not associate with CVD, and urinary IL-18 did not associate with either outcome. In contrast, albuminuria strongly associated with all-cause mortality and CVD. Future studies should evaluate reasons for these differences in the prognostic importance of individual kidney injury markers. PMID:24511130

  5. Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes.

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    Kawasaki, Takahiro; Ogata, Nobuyuki; Akanuma, Hiroshi; Sakai, Tadashi; Watanabe, Hiroyuki; Ichiyanagi, Kaoru; Yamanouchi, Toshikazu

    2004-05-01

    The aim of the present study was to investigate the association of fructose on microangiopathy in patients with diabetes. Postprandial plasma fructose concentrations and postprandial plasma glucose concentrations were simultaneously measured 3 times within a 24-hour period (2 hours after each meal) in 38 patients with type 2 diabetes that had been admitted to the hospital. The mean postprandial plasma fructose concentrations (MPPF) and the mean postprandial plasma glucose concentrations (MPPG) were calculated. Fructose was measured by gas chromatography-mass spectrometry (GCMS). Based solely on MPPF, we were able to divide the patients into three groups: the high MPPF (31.9 +/- 6.5 micromol/L) group (n = 12), the middle MPPF (21.2 +/- 1.8 micromol/L) group (n = 13), and the low MPPF (15.2 +/- 2.4 micromol/L) group (n = 13). Prevalence and degree of retinopathy and nephropathy were then evaluated in the 3 different groups. A significant correlation was observed in the prevalence of proliferative diabetic retinopathy (PDR) among the 3 MPPF groups (P =.024). The prevalence of PDR was higher in the high MPPF group (75.0%) than in the middle and low MPPF groups (23.1% and 38.5%, respectively). Although not significantly different statistically, the prevalence of all degrees of retinopathy showed a tendency to be higher in the high MPPF group (83.3%) than in the middle and low MPPF groups (46.2% and 46.2%, respectively) (P =.081). Nephropathy prevalence also showed a tendency to be higher in the high MPPF group (66.7%) than in the middle and low MPPF groups (38.5% and 30.8%, respectively), although the differences were not significant. The prevalence of clinical albuminuria was not significantly different among the 3 groups, but there was a tendency for it to be higher in the low MPPF group (30.8%) than in the high and middle MPPF groups (16.7% and 0%, respectively). No significant differences in glycemic indicators and mean duration of diabetes were observed among the 3

  6. Erythropoietin ameliorates podocyte injury in advanced diabetic nephropathy in the db/db mouse.

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    Loeffler, Ivonne; Rüster, Christiane; Franke, Sybille; Liebisch, Marita; Wolf, Gunter

    2013-09-15

    for a short time can ameliorate albuminuria and podocyte loss. PMID:23825071

  7. Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

    Science.gov (United States)

    Weir, Matthew R; Bakris, George L; Gross, Coleman; Mayo, Martha R; Garza, Dahlia; Stasiv, Yuri; Yuan, Jinwei; Berman, Lance; Williams, Gordon H

    2016-09-01

    Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors. PMID:27350174

  8. Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Ho, Wen-Chao [Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan (China); Caffrey, James L. [Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX (United States); Sonawane, Babasaheb [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States)

    2014-10-15

    Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues.

  9. DIABRISK - SL Prevention of cardio-metabolic disease with life style modification in young urban Sri Lankan's - study protocol for a randomized controlled trial

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    Viberti Giancarlo

    2011-09-01

    Full Text Available Abstract Background Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly lifestyle modification advice is superior to a less-intensive (12 monthly; control group lifestyle modification advice on a primary composite cardio-metabolic end point in 'at risk' urban subjects aged between 5-40 years. Methods/Design This is an open randomised controlled parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka. A cluster sampling strategy was used to select a large representative sample of subjects aged between 5-40 years at high risk of T2DM and CVD for the intervention study. We have screened 23,298 (males 47% females 53% healthy subjects for four risk factors: obesity, elevated waist circumference, family history of diabetes and physical inactivity, using a questionnaire and anthropometry. Those with two or more risk-factors were recruited to the intervention trial. We aim to recruit 4600 subjects for the intervention trial. The primary composite cardio-metabolic end point is; new onset T2DM, impaired glucose tolerance, impaired fasting glycaemia, new onset hypertension and albuminuria, following 5 years of intervention. The effect of the intervention on pre-specified secondary endpoints will also be evaluated. The study will be conducted according to good clinical and ethical practice, data analysis and reporting guidelines. Discussion DIABRISK-SL is a large population based trial to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk factors among young urban Sri-Lankans and the effect of a primary prevention strategy on cardio-metabolic disease end points. This work will enable country specific and regional cardio

  10. A maladaptive role for EP4 receptors in mouse mesangial cells.

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    Guang-xia Yang

    Full Text Available Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4 on extracellular matrix (ECM accumulation induced by TGF-β1 in mouse glomerular mesangial cells (GMCs remain unknown. Previously, we have identified that TGF-β1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox and EP4(+/- mice, cultured primary WT, EP4(Flox/Flox and EP4(+/- GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression and AD-Cre transfected EP4(Flox/Flox GMCs (EP4 deleted. We found that TGF-β1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-β1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-β1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx, WT and EP4(+/- mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr concentrations were significantly increased in WT mice as compared to those of EP4(+/- mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/- mice. The pathological changes in kidney of EP4(+/- mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/- mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-β1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis.

  11. Network of vascular diseases, death and biochemical characteristics in a set of 4,197 patients with type 1 diabetes (The FinnDiane Study

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    Wadén Johan

    2009-10-01

    Full Text Available Background Cardiovascular disease is the main cause of premature death in patients with type 1 diabetes. Patients with diabetic kidney disease have an increased risk of heart attack or stroke. Accurate knowledge of the complex inter-dependencies between the risk factors is critical for pinpointing the best targets for research and treatment. Therefore, the aim of this study was to describe the association patterns between clinical and biochemical features of diabetic complications. Methods Medical records and serum and urine samples of 4,197 patients with type 1 diabetes were collected from health care centers in Finland. At baseline, the mean diabetes duration was 22 years, 52% were male, 23% had kidney disease (urine albumin excretion over 300 mg/24 h or end-stage renal disease and 8% had a history of macrovascular events. All-cause mortality was evaluated after an average of 6.5 years of follow-up (25,714 patient years. The dataset comprised 28 clinical and 25 biochemical variables that were regarded as the nodes of a network to assess their mutual relationships. Results The networks contained cliques that were densely inter-connected (r > 0.6, including cliques for high-density lipoprotein (HDL markers, for triglycerides and cholesterol, for urinary excretion and for indices of body mass. The links between the cliques showed biologically relevant interactions: an inverse relationship between HDL cholesterol and the triglyceride clique (r P -16, a connection between triglycerides and body mass via C-reactive protein (r > 0.3, P -16 and intermediate-density cholesterol as the connector between lipoprotein metabolism and albuminuria (r > 0.3, P -16. Aging and macrovascular disease were linked to death via working ability and retinopathy. Diabetic kidney disease, serum creatinine and potassium, retinopathy and blood pressure were inter-connected. Blood pressure correlations indicated accelerated vascular aging in individuals with kidney disease

  12. Small dense low-density lipoprotein as a potential risk factor of nephropathy in type 2 diabetes mellitus

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    Essam Abd-Allha

    2014-01-01

    Full Text Available Background: The risk for diabetic nephropathy in type 2 diabetes is about 30-40%, and it is considered the leading cause of end-stage renal disease. Small dense low-density lipoprotein (sdLDL particles are believed to be atherogenic, and its predominance has been accepted as an emerging cardiovascular risk factor. This study aimed to assess small dense LDL as a potential risk factor and a possible predictor for diabetic nephropathy in type 2 diabetic patients. Patients and Methods: According to microalbuminuria test, 40 diabetic patients were categorized into two groups: Diabetic patients without nephropathy (microalbuminuria negative group and diabetic patients with nephropathy (microalbuminuria positive group, each group consists of 20 patients and all were non-obese and normotensive. The patients were re-classified into three sub-groups depending on the glomerular filtration rate (GFR. Results: The mean of small dense LDL level in the microalbuminuria positive group was higher than that in the microalbuminuria negative group, but without statistical significance. It was significantly higher in patients with either mild or moderate decrease in estimated GFR than in patients with normal estimated GFR. There was statistically significant correlation between small dense LDL and albuminuria and significant inverse correlation between small dense LDL and estimated GFR in all patients in the study. Based on microalbuminuria, the sensitivity and specificity of small dense LDL in the diagnosis of diabetic nephropathy was 40% and 80%, respectively, with cutoff values of small dense LDL >55.14 mg/dl. On the other hand, based on GFR, the sensitivity and specificity were 88.24% and 73.91% respectively, with cutoff values of small dense LDL >41.89 mg/dl. Conclusion: Small dense LDL is correlated with the incidence and severity of diabetic nephropathy in type 2 diabetic patients. It should be considered as a potential risk factor and as a diagnostic

  13. Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

    International Nuclear Information System (INIS)

    Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m2 and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214 had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues.

  14. Vascular endothelial growth factor-receptor 1 inhibition aggravates diabetic nephropathy through eNOS signaling pathway in db/db mice.

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    Keun Suk Yang

    Full Text Available The manipulation of vascular endothelial growth factor (VEGF-receptors (VEGFRs in diabetic nephropathy is as controversial as issue as ever. It is known to be VEGF-A and VEGFR2 that regulate most of the cellular actions of VEGF in experimental diabetic nephropathy. On the other hand, such factors as VEGF-A, -B and placenta growth factor bind to VEGFR1 with high affinity. Such notion instigated us to investigate on whether selective VEGFR1 inhibition with GNQWFI hexamer aggravates the progression of diabetic nephropathy in db/db mice. While diabetes suppressed VEGFR1, it did increase VEGFR2 expressions in the glomerulus. Db/db mice with VEGFR1 inhibition showed more prominent features with respect to, albuminuria, mesangial matrix expansion, inflammatory cell infiltration and greater numbers of apoptotic cells in the glomerulus, and oxidative stress than that of control db/db mice. All these changes were related to the suppression of diabetes-induced increases in PI3K activity and Akt phosphorylation as well as the aggravation of endothelial dysfunction associated with the inactivation of FoxO3a and eNOS-NOx. In cultured human glomerular endothelial cells (HGECs, high-glucose media with VEGFR1 inhibition induced more apoptotic cells and oxidative stress than did high-glucose media alone, which were associated with the suppression of PI3K-Akt phosphorylation, independently of the activation of AMP-activated protein kinase, and inactivation of FoxO3a and eNOS-NOx pathway. In addition, transfection with VEGFR1 siRNA in HGECs also suppressed PI3K-Akt-eNOS signaling. In conclusion, the specific blockade of VEGFR1 with GNQWFI caused severe renal injury related to profound suppression of the PI3K-Akt, FoxO3a and eNOS-NOx pathway, giving rise to the oxidative stress-induced apoptosis of glomerular cells in type 2 diabetic nephropathy.

  15. Catarata e diabetes mellitus tipo 1 Cataract and type 1 diabetes mellitus

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    Melissa Manfroi Dal Pizzol

    2008-08-01

    Full Text Available OBJETIVO: Avaliar a prevalência de catarata e seus fatores de risco em uma população portadora de diabetes mellitus tipo 1 (DM1. MÉTODOS: Estudo de casos e controles de um banco de dados de 181 pacientes (362 olhos com diagnóstico de diabetes mellitus tipo 1. Os pacientes foram classificados como casos quando apresentavam diagnóstico de catarata. As variáveis estudadas foram a presença ou não de retinopatia diabética, tratamento com panfotocoagulação, presença de hipertensão arterial sistêmica e neuropatia periférica, colesterol total, triglicerídios séricos, HDL, LDL, índice de massa corporal, creatinina sérica, albuminúria, hemoglobina glicosilada e glicemia de jejum. RESULTADOS: A prevalência de catarata foi de 19,9%. Na análise univariada foi encontrada associação estatisticamente significativa (pPURPOSE: To evaluate the prevalence of cataract and associated risk factors in a diabetic type 1 population. METHODS: 181 patients (362 eyes were evaluated in a case-control study. Cases were classified when cataract was present at the time of the examination. The studied outcomes were the presence of diabetic retinopathy, retinal panphotocoagulation, high blood pressure, peripheral neuropathy, total cholesterol levels, triglyceride levels, HDL, LDL, body mass index, creatinine levels, albuminuria, glycosylated hemoglobin and glycemia levels. RESULTS: Cataract was present in 19.9% of the studied patients. The association of the presence of cataract and diabetic retinopathy, peripheral neuropathy, elevated levels of creatinine, panphotocoagulation and high blood pressure were statistically significant (univariate analysis. After the logistic regression analysis the presence of cataract was significantly associated with the presence of diabetic retinopathy. CONCLUSION: The prevalence of cataract was 19.9% and the presence and severity of the diabetic retinopathy were the main risk factors for its development.

  16. The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

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    Davies M

    2016-06-01

    Full Text Available Melanie Davies,1,2 Sudesna Chatterjee,1,2 Kamlesh Khunti1,2 1Diabetes Research Centre, University of Leicester, 2Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK Abstract: Worldwide, an estimated 200 million people have chronic kidney disease (CKD, the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5 and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium

  17. Compromiso renal en pacientes HIV+ Renal abnormalities in HIV infected patients

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    María Marta Pernasetti

    2010-06-01

    Full Text Available Varias complicaciones nefrológicas pueden ocurrir durante la infección por el virus de la inmunodeficiencia humana (HIV especialmente en estadios avanzados de la enfermedad o relacionadas con otras infecciones o drogas. Poco conocida es la prevalencia de alteraciones renales subclínicas de pacientes HIV+ surgidas como complicación o relacionadas a la infección y/o tratamiento. Realizamos un corte transversal de pacientes asintomáticos HIV+ referidos en forma consecutiva al consultorio de nefrología para la detección de alteraciones nefrológicas. Se estudiaron 52 pacientes adultos mediante exámenes de sangre y orina, ultrasonido y biopsia renal. Edad media 39.9 ± 10.6 años, 88% varones, tiempo de diagnóstico de la infección: 53.2 ± 41.2 (2-127 meses. El 71% tenían síndrome de inmunodeficiencia adquirida (HIV-sida y el 77% recibían con antirretrovirales. La carga viral al momento del estudio fue 7043 ± 3322 copias y el recuento de CD4+ 484 ± 39 cel/mm³. El 30.7% presentó alteraciones del sedimento urinario: albuminuria: 16.6%, hematuria microscópica: 11.5%, hipercalciuria: 10.8% y cristaluria 6%. La media del filtrado glomerular fue 102.2 ± 22.9 ml/min (rango: 34-149. El 41% presentó anormalidades que corresponderían a enfermedad renal crónica (estadios 1 a 3. Los pacientes con alteraciones tenían mayor edad, con duración más prolongada de la infección. Las anomalías renales no se asociaron con mayor prevalencia de HIV-sida. Dos pacientes fueron biopsiados, con hallazgos de nefritis túbulo-intersticial crónica con cristales y glomerulonefritis por IgA. No hubo hallazgos de nefropatía por HIV. El amplio espectro y la alta prevalencia de anormalidades nefrológicas subclínicas encontradas sugieren que los pacientes asintomáticos HIV+ deberían realizar evaluaciones nefrológicas de rutina.Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious

  18. Study on the relationship of urinary liver-type fatty-acid binding protein and progression of nephropathy in diabetic patients%尿肝型脂肪酸结合蛋白与糖尿病肾病进展的关系研究

    Institute of Scientific and Technical Information of China (English)

    曾学辉; 李忠新; 张春雷; 宋林立

    2014-01-01

    Objective To investigate the relationship of urinary liver-type fatty-acid binding protein and progression of ne-phropathy in diabetic patients .Methods A total of 132 cases of type 1 and type 2 diabetic patients were recruited in this study , and were divided into four groups based on the urine albumin /creatinine and serum creatinine levels , including normal albuminuria group ( n =45), microalbuminuria group ( n =36), clinical albuminuria group ( n =30), and renal failure group ( n =21), Additional 65 healthy subjects were recruited as control group .The levels of urinary liver-type fatty-acid binding protein ( L-FABP) were measured with enzyme-linked immunosorbent assay (ELISA), and serum creatinine, urine creatinine, Liver function, hemoglobin, glycated he-moglobin (HbA1c), albumin (Alb), and 24h urinary protein were measured by respective biochemical or immunological methods . Results With the progression of diabetic nephropathy , the level of urinary L-FABP was gradually increased ( P 0.05).Conclusions The uri-nary L-FABP level can predict the occurrence of early diabetic nephropathy , and also monitor the progression of diabetic nephropathy .%目的:探讨尿肝型脂肪酸结合蛋白( L-FABP)与糖尿病肾病进展的关系。方法选择1型和2型糖尿病患者132例,依据尿蛋白/肌酐比(ACR)和血清肌酐水平分为正常蛋白尿组(45例),微量蛋白尿组(36例),临床白蛋白尿组(30例),肾功能衰竭组(21例),以65例健康体检者为对照组,酶联免疫吸附法( ELISA )测定尿L-FABP含量,同时检测血肌酐(Scr)、尿肌酐、肝功能、血红蛋白、糖化血红蛋白(HbA1c)、白蛋白(Alb)、24 h尿蛋白量、尿白蛋白等指标。结果随着糖尿病肾病的进展,尿L-FABP水平逐渐增高(各组间比较P <0.01),亚组分析显示正常白蛋白组尿L-FABP水平高于健康组( P<0.05),微量白蛋白组尿L-FABP水

  19. Avaliação do grau de inflamação vascular em pacientes com síndrome metabólica Evaluación del grado de inflamación vascular pacientes con síndrome metabólico Evaluation of the degree of vascular inflammation in patients with metabolic syndrome

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    Adriana Silva Monteiro Junqueira

    2009-10-01

    . Los marcadores inflamatorios se consideran factores de riesgo emergentes y pueden ser potencialmente utilizados en la estratificación clínica de las enfermedades cardiovasculares estableciendo valores pronósticos. OBJETIVO: Esta investigación tiene por objetivo evaluar qué componentes del síndrome metabólico presentan aumento de IL-6 y PCR-as, identificando el marcado que mejor expresa el grado de inflamación, y qué componente presenta en forma aislada mayor interferencia en los marcadores inflamatorios estudiados, a fin de identificar otros factores de riesgo importantes en la determinación de la inflamación arterial. METODOLOGIA: Se seleccionaron 87 pacientes, entre 26 y 85 años, hipertensos, diabéticos y dislipidémicos que obedecen a los criterios necesarios al diagnóstico de certidumbre de síndrome metabólico. Los pacientes se evaluaron mediante la MAPA de 24h y sometidos a análisis de PCR-as e IL-6, entre otras variables metabólicas. RESULTADOS: Los pacientes que presentaron PCR > 0,3mg/dl mostraron correlación significativa (P102/88 cm en el 83,7%; glicemia > 110mg/dl en el 88%; e IMC > 30kg/m² en el 60,5% de los individuos estudiados. CONCLUSIÓN: Se concluyó que la PCR fue el marcador inflamatorio de mayor expresión con relación a las variables estudiadas, siendo las de mayor relevancia estadística: tabaquismo, albuminuria, historia de cardiopatía personal previa, IMC, perímetro abdominal e hiperglicemia. La interleucina-6 no mostró correlación con ninguna variable estudiada.BACKGROUND: Metabolic Syndrome (MS is defined as a set of cardiovascular risk factors related to visceral obesity and insulin resistance that lead to an increase in general mortality, especially cardiovascular. The inflammatory markers are considered emergent risk factors and can be potentially used in the clinical stratification of cardiovascular diseases, establishing prognostic values. OBJECTIVE: This study aims at evaluating which components of the MS

  20. The Expression and Significance of Heparanase In Human chronic kidney diseases%乙酰肝素酶在慢性肾脏疾病患者肾组织中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    廖丹; 白云凯; 肖欢; 李红

    2012-01-01

    ,and contrasted with the Control Group,it has the statistics difference(P < 0.01).Dependablity between Hpa and clinical index: Hpa has positive correlation with 24 hour Urine protein quantitation r =0.5407(P < 0.01),negative correlation with plasma-albumin r =-0.6948(P < 0.01),which are statistics significance.It has no dependablity with serum creatinine,blood fat,immune globulin.Conclusions The express of Hpa has positive correlation with albuminuric extent,which demostrates that Hpa,one enzyme closely connected with albuminuria,has been arising the interests and reconstruction of the public and will become a new target of albuminuric therapy.

  1. 广西贺州城镇成人慢性肾脏病的流行病学调查%Epidemiologic investigation of chronic kidney disease in adult urban population of Hezhou Guangxi

    Institute of Scientific and Technical Information of China (English)

    廖蕴华; 彭育欢; 陈强文; 苏飞群; 周翠屏; 黎水莲; 潘玲; 陈青云; 黄莉; 霍冬梅; 宋雅珊; 陈莹; 唐曦平; 马健皓

    2008-01-01

    Objective To investigate the prevalence and risk factors of chronic kidney disease (CKD) in the adult urban population of Hezhou Guangxi. Methods One thousand and two hundred urban residents (older than 18 years) from Hezhou Guangxi were randomly selected using a random sampling. All the residents were interviewed. Their morning spot urine were tested to determine albumin to ereatinine ratio (abnormal:≥30 mg/g), and renal function [abnomal: eMDRD <60 ml·min-1·(1.73 m2)-1] was assessed. Morning spot urine dipstick of hematuria (abnormal:≥1 +) was confirmed by microscopy (abnormal: 3 red blood cells/HP). The associations among demographic characteristics, health eharacteristies and indicators of kidney damage were examined. Results Eligible data of 1069 subjects were enrolled in the study. The prevalence of albuminuria was 7.5%, hematuria 4.8%, and reduced eGFR 3.6%. The prevalence of kidney disease was 14.4% and the recognition was 1.4%. Age (OR 1.022, 95%CI 1.008-1.035), gender (OR 2.249, 95%CI 1.502-3.367), diabetes mellitus (OR 7.422, 95%CI 3.985-13.825) and hypertension (OR 4.397, 95% CI 2.601-7.432) were independently associated with CKD. Conclusions The prevalence of chronic kidney disease is 14.4% and the recognition is 1.4% in adult urban population of Hezhou Guangxi. Independent risk factors associated with chronic kidney disease are age, gender, diabetes mellitus and hypertension which is similar to those in developed countries and domestic big cities.%目的 探讨广西贺州城镇成人慢性肾脏病(CKD)的患病情况及危险因素.方法 在广西中小城市贺州,采用分层整群系统随机抽样的方法,抽取贺州部分城镇1200名18岁以上的常住居民,对其进行问卷调查、检测肾脏损伤指标及相关危险因素.结果 在资料完整的1069名居民中,白蛋白尿的患病率为7.5%;血尿的患病率为4.8%,肾功能下降的患病率为3.6%.该人群CKD的患病率为14.4%,知晓率为1.4%.二分类Logistic回

  2. The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II – Therapy

    Science.gov (United States)

    Khan, Nadia A; McAlister, Finlay A; Rabkin, Simon W; Padwal, Raj; Feldman, Ross D; Campbell, Norman RC; Leiter, Lawrence A; Lewanczuk, Richard Z; Schiffrin, Ernesto L; Hill, Michael D; Arnold, Malcolm; Moe, Gordon; Campbell, Tavis S; Herbert, Carol; Milot, Alain; Stone, James A; Burgess, Ellen; Hemmelgarn, B; Jones, Charlotte; Larochelle, Pierre; Ogilvie, Richard I; Houlden, Robyn; Herman, Robert J; Hamet, Pavel; Fodor, George; Carruthers, George; Culleton, Bruce; deChamplain, Jacques; Pylypchuk, George; Logan, Alexander G; Gledhill, Norm; Petrella, Robert; Tobe, Sheldon; Touyz, Rhian M

    2006-01-01

    mellitus or chronic kidney disease (regardless of the degree of proteinuria). Most adults with hypertension require more than one agent to achieve these target BPs. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers or angiotensin receptor antagonists. Other agents for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers or angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or in patients without albuminuria, thiazides or dihydropyridine calcium channel blockers) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy. VALIDATION All recommendations were graded according to strength of the evidence and voted on by the 45 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95

  3. Epidemiology investigation of chronic kidney disease among adults in Yongchuan of Chongqing%重庆市永川区成人慢性肾脏病流行病学调查

    Institute of Scientific and Technical Information of China (English)

    罗华丽; 蒋先洪; 文津; 马艳萍; 夏庆红; 黎洋; 胡煜琳; 孙劦义

    2014-01-01

    目的:探讨重庆市永川区成人体检人群中慢性肾脏病(CKD)的患病率及相关危险因素。方法抽取2012年1月至2013年10月于重庆医科大学附属永川医院、重庆永川区人民医院和重庆永川区中医院进行健康体检的10280例18岁以上的常住居民,筛选体检资料确定CKD人群,进行问卷调查、体格检查和肾脏损伤及相关危险因素长达3个月的监测。结果在10021例资料完整的体检人群中,清蛋白尿、血尿、估算肾小球滤过率(eGFR)<60 mL · min-1·1.73 m -2的患病率分别为5.1%、8.3%、1.4%。该人群CKD的患病率为15.7%,知晓率为6.4%。多因素Logistic回归提示,高尿酸血症、肾结石、糖尿病、高血压、肥胖、年龄是CKD的危险因素。结论在重庆永川地区体检人群中,CKD的患病率为15.7%;知晓率为6.4%。CKD的相关危险因素包括高尿酸血症、肾结石、糖尿病、高血压、肥胖和年龄。%Objective To study the prevalence of chronic kidney disease(CKD) and risk factors among adults received examina-tion in Yongchuan district of Chongqing .Methods 10 280 residents(older than 18 years) were selected ,who had health examina-tion in the Yongchuan Affiliated Hospital ,Chongqing Medical University ,Yongchuan Hospital of Traditional Chinese Medicine and Yongchuan people's hospital from January 2012 to December 2013 .Patients with CKD were identified by the examination dates .All of them were conducted with a questionnaire survey ,physical examination ,and renal damage and related risk indicator factors moni-toring for more than 3 months .Results Eligible dates of 10 021 subjects were enrolled in the study .The prevalence of albuminuria was 5 .1% ,hematuria in 8 .3% ,reduced renal function in 1 .4% .The CKD population prevalence rate was 15 .7% ,and the recogni-tion was 6 .4% .The Logistic regression model showed that hyperuricemia ,nephrolithiasis ,diabetes

  4. Effectiveness of the introduction of a Chronic Care Model-based program for type 2 diabetes in Belgium

    Directory of Open Access Journals (Sweden)

    De Maeseneer Jan

    2010-07-01

    .90%. The improvement in lipid control was significantly higher (p = 0.0021 in the intervention region (total cholesterol 199.07 to 173 mg/dl than in the control region (199.44 to 180.60 mg/dl. The systematic assessment of long-term diabetes complications remained insufficient. In 2006 only 26% of the patients had their urine tested for micro-albuminuria and only 36% had consulted an ophthalmologist. Conclusion Although the overall ACIC score increased from 1.45 to 5.5, the improvement in the quality of diabetes care was moderate. Further improvements are needed in the CCM components delivery system design and clinical information systems. The regional networks, as they are financed now by the National Institute for Health and Disability Insurance (NIHDI, are an opportunity to explore how this can be achieved in consultation with the GPs. But it is clear that, simultaneously, action is needed on the health system level to realize the installation of an accurate quality monitoring system and the necessary preconditions for chronic care delivery in primary care (patient registration, staff support, IT support. Trial Registration Trial registration number: ClinicalTrials.gov Identifier: NCT00824499

  5. Glomerulonephritis in schistosomiasis mansoni: a time to reappraise Glomerulonefrite na esquistossomose mansônica: um tempo para reavaliar

    Directory of Open Access Journals (Sweden)

    Valério Ladeira Rodrigues

    2010-12-01

    Full Text Available INTRODUCTION: The current prevalence of glomerulonephritis in patients with hepatosplenic schistosomiasis mansoni in Brazil was evaluated. METHODS: Sixty three patients (mean age 45.5±11 years attending the outpatient infectious disease clinic of a University Hospital in Belo Horizonte, Brazil, from 2007 to 2009, were consecutively examined and enrolled in the present investigation. Diagnosis of hepatosplenic schistosomiasis was based on epidemiological, clinical and parasitological data and imaging techniques. Eight patients, who presented >30mg/day albuminuria, were submitted to percutaneous ultrasound guided renal biopsy. Kidney tissue fragments were examined under light, direct immunofluorescence and electron microscopy. RESULTS: All patients showed mesangial enlargement. In five, mesangial hypercellularity was observed and four presented duplication of the glomerular basement membrane. Areas of glomerular sclerosis were diagnosed in four. Deposits of immunoglobulin M and C3 were present in six samples; deposits of IgG in four, IgA in three and C1q in two samples. In all patients, immunoglobulin A was reported in the lumen of renal tubules. Deposits of kappa and lambda were observed in six samples. Electron microscopy revealed dense deposits in the glomerular tissue of three patients. Arterial hypertension, small esophageal varices, slight increases in serum creatinine and decreases in serum albumin were associated with glomerular disease. CONCLUSIONS: Renal disease associated with hepatosplenic schistosomiasis was verified in 12.7% of patients and type I membranoproliferative glomerulonephritis was observed in 50% of them. Schistosomal glomerulopathy still is an important problem in patients with hepatosplenic schistosomiasis in Brazil.INTRODUÇÃO: Avaliou-se a frequência de glomerulonefrite em pacientes com esquistossomose hepatosplênica no Brasil. MÉTODOS: Selecionou-se para o estudo, 63 pacientes (idade média de 45,5±11 anos

  6. 2型糖尿病患者胃排空影响因素分析%Analysis on Factors Influencing Gastric Emptying in Patients with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    陈琳; 喻明; 顾新刚

    2011-01-01

    exhibited slower gastric emptying. Patients with high - grade albuminuria also had longer emptying time than those without albumin in their urine. Negative correlation was found between patients' emptying time and serum vitamin B12 levels. Similar result was ob-served between emptying time and 2 -hour postprandial blood glucose. Conclusions Gastric emptying can be well evaluated by ultrasound. Patients with long - period hyperglycemia may have extended gastric emptying. Diabetic gastroparesis probably has some sort of relationship with chronic microvascular disease and vitamin B12 deficiency. Extended gastric emptying may help to reduce glucose fluctuation after meals by postponing carbohydrate absorption.

  7. Measurement of renal function by calculation of fractional uptake of technetium-99m dimercaptosuccinic acid

    International Nuclear Information System (INIS)

    The purpose of this study was to set up normal values of the fractional uptake (FU) of technetium-99m dimercaptosuccinic acid in adults and in the pediatric population, as well as to evaluate the validity of this parameter at different levels of renal function. A total of 86 subjects was divided into seven groups. In group A there were 23 potential kidney donors and in group B, 18 children in remission after a first urinary tract infection. Another three groups consisted of patients with diabetes i.e. group C, seven patients with normal values of albuminuria, group D, 16 patients with microalbuminuria and group E, five patients with macroalbuminuria. In group F, there were ten patients with a well-functioning transplanted kidney and in group G, seven patients with suspected acute rejection. The procedure began with the quantification of the doses of 99mTc-DMSA to be injected and the measurement of the empty syringe lying on the gamma camera collimator. Thereafter, four planar views of the kidneys were acquired three hours after the injection. The counts from the posterior and anterior views were subtracted for background and corrected for radioactive decay time and patient thickness. The FU was calculated by the geometric mean of counts per second from the posterior and anterior view. It was expressed as a fraction of the injected dose. The mean values of FU in healthy adults were 0.227 ± 0.077 for one kidney and 0.454 ± 0.146 for both kidneys. The mean values of FU for the left and right kidney were 0.225± 0.071 and 0.229 ± 0.079, respectively. In children, the mean values were 0.220 ± 0.092 for one kidney and 0.432 ± 0.094 for both kidneys. The highest values of FU of 0.322 ± 0.078 (0.644 ± 0.138 for both kidneys) were measured in group C. In group D, FU was 0.185 ± 0.065 (0.361 ± 0.125 for both kidneys) and in group E 0.082 ± 0.040 (0.163 ± 0.080 total). In patients with a transplanted kidney, fractional uptake was 0.162 ± 0.039 in group F and 0

  8. 自发性2型糖尿病动物模型KKAy小鼠肾脏损害的特征与演变%Renal Impairment in KKAy Mice with Spontaneous Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    刘晓丹; 杨刚; 范秋灵; 刘楠; 栗霄立; 冯江敏

    2011-01-01

    目的 观察自发性2型糖尿病动物模型KKAy小鼠糖尿病早期肾损害的特征和演变,旨在探讨其在糖尿病肾病研究中的应用价值.方法 选择8周龄雄性KKAy小鼠和C57BL/6小鼠各20只,分别于8周龄、20周龄测定血糖、尿微量白蛋白、尿肌酐,并留取肾脏标本,于光镜及电镜下观察其肾脏病理特点.结果 不同周龄KKAy小鼠体质量、随机血糖均高于对照组C57BL/6小鼠(P<0.05).20周龄KKAy小鼠尿白蛋白排泄率显著高于8周龄KKAy小鼠和对照组C57BL/6小鼠(P<0.05).20周龄KKAy小鼠光镜下肾小球面积增大,肾小球毛细血管基底膜增厚,系膜基质增生,可见硬化结节;电镜下肾小球基底膜增厚,足突部分扁平、融合.结论 20周龄KKAy小鼠出现肥胖、高血糖、尿白蛋白排泄率增加及典型的糖尿病肾病病理改变,是研究2型糖尿病早期肾损害的理想动物模型.%Objective To investigate the early renal impairment in KKAy mice with spontaneous type 2 diabetes. Methods Blood glucose, urinary microalbumin and urinary creatinine of twenty male KKAy mice and twenty male C57BL/6 mice were measured at the age of 8,20 weeks respectively. The renal pathological changes were observed under light microscope and electron microscope. Results KKAy mice developed higher body weight and blood glucose than C57BL/6 mice at all the different ages (P < 0.05 ). Urinary microalbumin/creatinine ratio in 20-week-age KKAy mice was higher than that in 8-week-age KKAy mice and C57BL/6 mice (P < 0.05 ). Pathological lesions in 20-week-age KKAy mice were increasing of glomendar area, thickening of glomerular basement membrane, expansion of mesangial matrix,with sclerosis lesions under light microscope; thickening of basement membrane and fusion of foot processes were evident under electron mieroecope. Conclusion KKAy mice developed obesity, hyperglycemia, albuminuria and typical pathological lesions of diabetic nephropathy at 20 weeks of age

  9. The use of Aspirin in Primary Prevention of cardiovascular disease: new updates El uso de la Aspirina en la Prevención Primaria de la enfermedad cardiovascular: nuevas actualizaciones O uso da Aspirina na Prevenção Primária da doença cardiovascular: novas atualizações

    Directory of Open Access Journals (Sweden)

    Luís Filipe Cavadas

    2011-06-01

    Full Text Available

    Many times the Family Physicians need to make the decision of start to use or not aspirin in their patients. Although the benefits of treatment with aspirin in reducing the risk of myocardial infarction (MI, stroke or vascular cause of death among men and women with pre-existing cardiovascular disease (CVD are well established, the role of aspirin in primary prevention is less clear. So, the objective of this work is to determine the indications of aspirin use for the primary prevention of CVD in adults, based in the best available evidence. The author searched evidence-based reviews, guidelines, meta-analysis, systematic reviews and randomized controlled trials, in Medline database and evidence-based medicine sites, using the MeSH terms: “Aspirin and Primary Prevention”. The search was limited to articles published between January 2000 and December 2009 in English, Spanish and Portuguese. The Strength of Recommendation Taxonomy (SORT of the American Family Physician was used to assess the Level of Evidence. The conclusions are: the men between 45 and 79 years should be encouraged to use aspirin if the potential cardiovascular benefit, prevention of MI, outweighs the potential damage of gastrointestinal (GI bleeding (SOR A; the women between 55 and 79 years should be encouraged to use aspirin if the potential cardiovascular benefit, the prevention of stroke, outweighs the potential damage of GI bleeding (SOR A; aspirin can reduce the risk of MI in the diabetic males (SOR B; consider the use of aspirin for primary prevention of CVD in diabetes type 1 and type 2 with increased cardiovascular risk, including those aged >40 years or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, and albuminuria ( SOR B.

    A menudo, los médicos de familia tienen que decidir se inician o no el uso de la aspirina en los pacientes. Aunque los beneficios de la terapia con aspirina en la reducción del riesgo de

  10. 醛固酮对肾小球系膜细胞凋亡的影响%Effect of aldosterone on glomerular mesangial cells apoptosis bothin vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    任志龙; 梁伟; 丁国华; 胡凤琪; 杨红霞

    2011-01-01

    Objective To evaluate the effect of aldosterone (Ald) on glomerular mesangial cells apoptosis and to explore the possible mechanisms.Methods Twenty-four Sprngue-Dawley rats were subcutaneously embedded with osmotic mini-pumps and randomly divided into 3 groups.Aldosterone (1.5 μg/h) was administrated subcutaneouly by osmotic mini-pumps in Ald group,eplerenone (Epl,100 mg·kg-1·d-1) and Ald (1.5 μg/h) was given to Epl group.And normal saline was used in control group (Con group).Systolic blood pressure and urinary albumin excretion rate (UAER) were detected on day 0,7,14,21,28.Blood and kidney samples were harvested on day 28.Plasma creatinine,potassium and aldosterone were measured.Renal paraffin sections were stained by PAS and the morphological changes were evaluated by light microscopy.Apoptosis index of mesangial cells were detected by TUNEL assay.The glomerular mesangial cells (MCs) were cultured in a DMEM-F12 media.MCs apoptosis was evaluated by staining cells with Annexin V and propidium iodide (PI) using flow cytometer.Expression of Bcl-2 and Bax mRNA was examined by RT-PCR.The protein level of Bad or phospho-Bad was measured by Western blotting.Results Ald-infused rats developed hyperaldosteronemia and hypokalemia.Rats in Ald group exhibited significant hypertension and marked albuminuria.Ald group rats showed increased number of TUNEL-positive mesangial cells when compared with control rats (P<0.05).Aldosterone induced mesangial cells apoptosis in a time-dependent manner.Expression of Bcl-2 mRNA was decreased but Bax mRNA was increased in aldosterone treated MCs compared to that in Con group (P<0.05).Aldosterone promoted dephosphorylation of cytosolic phospho-Bad compared with vehicle treated cells (P< 0.05).However,eplerenone attenuated these effects of aldosterone.Conclusion Aldosterone directly promotes mesangial cells apoptosis,and eplerenone can attenuate this effect of aldosterone.Dephosphorylation of cytosolic phospho-Bad may be the key

  11. 192例IgA肾病临床与牛津病理分型的分析%Analysis of the clinical characteristics and the Oxford classification of 192 cases of IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    马也娉; 李荣山; 王晨; 乔玉峰; 高丽芳

    2013-01-01

    目的 探讨IgA肾病患者的临床表现与牛津病理分型的相关性.方法 分析192例IgA肾病患者的临床表现(年龄、性别、病程、血压、血尿、24 h尿蛋白定量、血肌酐、血清白蛋白、甘油三酯、胆固醇、估计肾小球滤过率(eGFR))与病理资料(系膜细胞增生、内皮细胞增生、节段硬化或粘连、肾小管萎缩或间质纤维化、小动脉积分、细胞或细胞纤维新月体)的相关性.结果 (1)192例IgA肾病患者临床表现以蛋白尿合并血尿最多见,为72例(37.5%),依次为肾病综合征42例(21.9%),肾功能不全29例(15.1%),合并高血压72例(37.5%);(2)牛津病理分型中M1占60.0%,E1占55.2%,S1占46.9%,T0、T1、T2分别占59.9%、22.9%、17.2%,46.9%的患者存在小动脉内膜增厚,48.5%存在细胞或细胞纤维新月体,部分病理类型与年龄有关(P<0.01);(3)尿蛋白定量与系膜细胞增生、肾小管萎缩或间质纤维化、细胞或细胞纤维新月体有关(P <0.01或P<0.05).血压、肾功与节段硬化或粘连、肾小管萎缩或间质纤维化、小动脉内膜增厚、细胞或细胞纤维月体有关(P<0.01或P<0.05).结论 牛津病理分型对IgA肾病的治疗和预后评价有很好的指导作用.%Objective To investigate the relationship of the clinical characteristics and the Oxford classification of IgA nephropathy.Methods Clinical presentation (age,gender,course of disease,blood pressure,hematuria,24-hour proteinuria,serum creatinine,serum albumin,triglyceride,cholesterol,and estimated glomerular filtration rate (eGFR)),pathological data (mesangial hypercellularity,endocapillary hypercellularity,segmental sclerosis or adhesions,tubular atrophy or interstitial fibrosis,artery score,and cellular + fiberocellular crescents) and their correlation of 192 patients with IgA nephropathy patients were analyzed.Results (1)Clinically,hematuria + albuminuria type was the most common among 192 the patients

  12. 5708例健康体检人群中慢性肾脏疾病的调查分析%Chronic kidney disease in 5 708 people receiving physical examination

    Institute of Scientific and Technical Information of China (English)

    徐果; 陈志恒; 张浩; 龚妮; 王艳

    2014-01-01

    rate of albuminuria, reduced renal function and hematuria was 25.0%, 1.7% and 1.1%. hTe detection rate of CKD was 25.6%, and detection rate of CKD stage 1-5 was 17.8%, 6.7%, 1.1%, 0 and 0, respectively. Multivariate logistic analysis indicated that diabetes mellitus, hypertension, hypercholesterolemia, male, age, and smoking were the risk factors for CKD. Increasing physical activity was the protective factor against CKD. Conclusion: High prevalence of CKD in people receiving physical examination is found in Changsha, especially stage 1 and 2 CKD. Physical examination is important to screen CKD. Stopping smoking, control of blood glucose, blood pressure, blood lipids and increasing physical activity may help reduce the prevalence of CKD.

  13. 尿胞外体亮氨酸氨基肽酶及二肽基肽酶在糖尿病肾病中的变化%Changes of urinary exosomal leucine aminopeptidase and dipeptidyl peptidase 4 in diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    孙爱丽; 胡晓燕; 关广聚; 邓浩萍; 刘元涛; 陈诗鸿; 刘军莉; 邓景惕

    2011-01-01

    AIM: To investigate the changes of urinary exosomal enzymes and the correlation with diabetic nephropathy.METHODS: Thirty - four healthy volunteers and 127 patients of type 2 diabetes mellitus ( T2DM ) were included in the study.The healthy volunteers served as control.The patients with T2DM were divided into 3 groups based on their 24 h urinary albumin/creatinine ratio ( UACR ): 50 patients with microalbuminuria in early DN group ( DN1 ), 34 patients with macroalbuminuria in overt DN group ( DN2 ) and 43 patients without albuminuria in DM group.The levels of urine exosomal leucine aminopeptidase( exosome - LAP ) and exosomal dipeptidyl peptidase 4( exosome - DPP4 ) were determined by enzyme - linked immunosorbent assay ( ELISA ).The following methods were used to determine the biochemical parameters: liquid chromatography for glycated hemoglobin ( HbA1c ), chemical modification method for cholesterol ( CH ), Jaffe - kinetic assay for creatinine ( CR ) and urease - GLDH method for blood urea nitrogen ( BUN ).Multiple stepwise linear regressions were used to analyze the relationship of exosome - LAP or exosome - DPP4 with HbA1c, CH, UACR, CR and BUN.RESULTS: The levels of exosome - LAP and exosome - DPP4 in DM, DN1 and DN2 groups were significantly higher than those in control group ( P <0.01 ).The exosome - LAP in DN2 group was significantly higher than that in DM group.Correlation analysis showed that the levels of urinary exosome - LAP and exosome - DPP4 were positively correlated with HbA1c, CH, UACR, CR and BUN.Multiple stepwise linear regression analysis showed that CH and UACR were independent determinants for exosome - LAP ( P <0.01 ), and UACR and HbAlc were independent determinants for exosome - DPP4 ( P <0.01 ).CONCLUSION: Urine exosome - LAP and exosome - DPP4 are correlated with the severity of diabetic nephropathy.These parameters may serve as clinical markers for the diagnosis and prognosis evaluation of diabetic nephropathy.%目的:探讨 2

  14. CLINICAL PROFILE OF NON-ALBUMINURIC RENAL INSUFFICIENCY IN TYPE 2 DIABETES MELLITUS IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    P. Sathya Murthy

    2016-07-01

    Full Text Available INTRODUCTION Diabetes mellitus is one of the most prevalent metabolic diseases which is characterised by elevated blood sugar levels. Type 2 diabetes mellitus constitutes about 90 percent of this group. Untreated DM leads to many complications which are traditionally classified as acute and chronic. The microvascular complications include retinopathy, nephropathy and peripheral neuropathy. Diabetic nephropathy is the most common cause for dialysis and end-stage renal failure across the world. Diabetic nephropathy usually starts with microalbuminuria (UAE 30-300 mg/dL followed by macroalbuminuria (UAE > 300 mg/dL and eventually there is progressive loss of renal function by tissue scarring leading on to end-stage renal disease. However, in type 2 DM, there can be a group of patients who can have impaired renal function without albuminuria (UAE<30 mg/ day. This is being called as “non-albuminuric renal failure”. Reduced GFR in long duration diabetic patients with normal urine albumin excretion have been reported in increasing frequency. There are very few Indian studies which have been done on this group of type 2 diabetic patients. Hence, this study is aimed to evaluate the clinical profile of non-albuminuric renal insufficiency in type 2 diabetes mellitus. AIM To study the clinical profile of non-albuminuric renal insufficiency in type 2 DM. MATERIALS AND METHODS The study population included 97 patients with non-albuminuric (urine microalbumin less than 30 mg/day, renal insufficiency (GFR less than 60 mL/min. as per Cockcroft–Gault formula and are diabetic (type 2 admitted in the Department of General Medicine and Nephrology. Patients with comorbidities other than diabetes which can cause renal insufficiency were excluded from the study. A detailed history was taken and clinical assessment was done for all patients. All patients underwent a panel of tests which included complete blood count, blood urea nitrogen, serum creatinine

  15. The impact of urinary schistosomiasis and praziquantel treatment on the nutritional status of Sudanese schoolchildren: a double Blind Placebo controlled study

    International Nuclear Information System (INIS)

    only after one year of taking the praziquantel treatment (t-value =18, p=0.0001). Haematuria and albuminuria were reduced by one half in the praziquantel group, whereas increased significantly in the placebo group. The rate of splenomegaly decreased in the praziquantel group, while in the placebo group. It increased, but the difference was found insignificant. The study concluded that: Praziquantel treatment efficiently reduced S. haematobium morbidity and positively and significant raised Hb and serum ferritin levels. Moreover, the high t of the children was significantly increased after one year. Additional gains in nutritional status would be expected if malaria was concurrently treated and the dietary gap between the villages and town was reduced

  16. The 2008 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

    Science.gov (United States)

    Khan, Nadia A; Hemmelgarn, Brenda; Herman, Robert J; Rabkin, Simon W; McAlister, Finlay A; Bell, Chaim M; Touyz, Rhian M; Padwal, Raj; Leiter, Lawrence A; Mahon, Jeff L; Hill, Michael D; Larochelle, Pierre; Feldman, Ross D; Schiffrin, Ernesto L; Campbell, Norman RC; Arnold, Malcolm O; Moe, Gordon; Campbell, Tavis S; Milot, Alain; Stone, James A; Jones, Charlotte; Ogilvie, Richard I; Hamet, Pavel; Fodor, George; Carruthers, George; Burns, Kevin D; Ruzicka, Marcel; deChamplain, Jacques; Pylypchuk, George; Petrella, Robert; Boulanger, Jean-Martin; Trudeau, Luc; Hegele, Robert A; Woo, Vincent; McFarlane, Phil; Vallée, Michel; Howlett, Jonathan; Katzmarzyk, Peter; Tobe, Sheldon; Lewanczuk, Richard Z

    2008-01-01

    the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered for initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with protein-uric nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension but who do not achieve thresholds for statin therapy

  17. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

    Science.gov (United States)

    Khan, Nadia A; Hemmelgarn, Brenda; Padwal, Raj; Larochelle, Pierre; Mahon, Jeff L; Lewanczuk, Richard Z; McAlister, Finlay A; Rabkin, Simon W; Hill, Michael D; Feldman, Ross D; Schiffrin, Ernesto L; Campbell, Norman RC; Logan, Alexander G; Arnold, Malcolm; Moe, Gordon; Campbell, Tavis S; Milot, Alain; Stone, James A; Jones, Charlotte; Leiter, Lawrence A; Ogilvie, Richard I; Herman, Robert J; Hamet, Pavel; Fodor, George; Carruthers, George; Culleton, Bruce; Burns, Kevin D; Ruzicka, Marcel; deChamplain, Jacques; Pylypchuk, George; Gledhill, Norm; Petrella, Robert; Boulanger, Jean-Martin; Trudeau, Luc; Hegele, Robert A; Woo, Vincent; McFarlane, Phil; Touyz, Rhian M; Tobe, Sheldon W

    2007-01-01

    grains and protein from plant sources; and considering stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual’s global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with

  18. A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.

    Science.gov (United States)

    Simmons, Rebecca K; Borch-Johnsen, Knut; Lauritzen, Torsten; Rutten, Guy Ehm; Sandbæk, Annelli; van den Donk, Maureen; Black, James A; Tao, Libo; Wilson, Edward Cf; Davies, Melanie J; Khunti, Kamlesh; Sharp, Stephen J; Wareham, Nicholas J; Griffin, Simon J

    2016-01-01

    in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient. CONCLUSIONS Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted. TRIAL REGISTRATION ClinicalTrials.gov NCT00237549. FUNDING DETAILS This project was funded by the NIHR Health

  19. Inhibitory effects of benazepril on the formation of advanced glycosylation end products and kidney injury in spontaneous hypertension rats%贝那普利对自发性高血压大鼠糖基化终末产物形成及肾脏损伤的抑制

    Institute of Scientific and Technical Information of China (English)

    朱艳利; 扈丽萍; 侯训尧; 刘雪平

    2011-01-01

    calculated. Expressions of AGEs and vascular cell adhesion molecule-1 (VCAM-1) in the kidneys were detected by immunofluores-cence assay. Expressions of nuclear transcription factor( NF-kB ) mRNA and triphosphopyridine nucleotide( NADPH) oxidase p47phox mRNA were measured by RT-PCR. Expression of the NF-kB protein was measured by Western blot. Results Compared with the WKY group, the levels of Ang II in the kidneys, albuminuria and GSI were significantlyhigher in the SHR group(P<0.01), while they were significantly reduced by benazepril(P<0.01). Compared with the WKY group, expressions of AGEs, VCAM-1, NF-kB and NADPH oxidase p47phox were significantly higher in the SHR group( P < 0.01), while they were significantly reduced by benazepril (P < 0.01). Conclusion Oxidation stress in the kidneys is increased in SHR. Combination of AGEs and RAGE can activate NF-kB, increased expressions of VCAM and NADPH oxidase p47phox, and accelerate injury to kidneys. By suppressing oxidative stress and expressions of AGEs, benazepril further inhibits expressions of NF-kB and growth factor and eases injury to kidneys induced by hypertension.

  20. An analysis on importance of drugs in traditional Chinese medicine for treatment of complications and symptoms of hypertension by QUEST algorithms%基于QUEST算法的高血压辨病对症治疗中药的重要性分析

    Institute of Scientific and Technical Information of China (English)

    郑文龙; 陈启兰; 陈辉珍; 祝光礼

    2015-01-01

    Objective To approach Professor Zhu Guangli's regular pattern of differentiation of symptoms and signs in patients with hypertension accompanied by complications and in accord with the individual manifestations to add or subtract the ingredients in the prescription.Methods The patients with essential hypertension selected were those who the first time came to the Affiliated Guangxing Hospital of Zhejiang Chinese Medical University or Hangzhou Hospital of Traditional Chinese Medicine (TCM) of Zhejiang Province from September 2012 to January 2015, and were continuously followed up in the hospitals having their clinical data comprehensive. The complications, combination diseases and symptoms of hypertension were conducted as dependent variables, while the applied Chinese medicines were acted as independent variables. QUEST algorithms were employed to analyze the different dependent variables to evaluate the importance contribution rate (ICR) of every kind of Chinese medicine.Results There were 9 types of complications or combination diseases [including hyperlipemia, coronary heart disease, cardiac arrhythmia, hyperglycemia, trace albuminuria, lacunar cerebral infarction, elevation of creatinine in blood (azotemia), liver dysfunction and cardiac dysfunction] and 39 types of symptoms obtained (including dizziness, palpitation, chest oppression, insomnia, lack of strength, soreness of the waist and knees, dry mouth, loose stool, fatigue, apontaneous sweating, headache, shortness of breath, coprostasis, fullness in the stomach, blurred vision, limb numbness, low spirit, chest pain, poor appetite, abdominal distension, excessive dreaming, tinnitus, flush of the face, neck rigidity, hectic fever, bitterness in the mouth, cough, ructus, nocturia, fremitus, stenagma, pharyngalgia, heaviness in head, nocturnal sweating, frequent urination, coughing of sputum, chillness and cold limbs, aphthous stomatitis and sialosis) being the QUEST decision models. All kinds of the TCM

  1. Intoxicação por veneno de cobra: necrose symetrica da cortex renal: uremia

    Directory of Open Access Journals (Sweden)

    A. Penna de Azevedo

    1938-01-01

    symmetrical cortical necrosis. Among the changes of greater significance there are, moreover, observed vascular injuries of great intensity and essentially constituted by a process of productive endoarteritis. The necrosis of the cortex renis, in view of the intensive vascular changes (productive endoarteritis conveying the obliteration of the arteries, is considered as a direct consequence of such vascular changes. The renal vessels, which are the seat of the inflammatory process, are the interlobar, arciform and interlobular arteries, but mainly the arteriolary ramifications of the cortical layer. The process of endoarteritis always assumes a progressive character so that the vascular lumen, little by little, is getting obstructed. In opposition to what has been observed in the cases, quoted in the literature, of symmetrical necrosis of the cortex, in which the parenchymatous changes are consecutive to thrombosis of the renal vessels, in the present case this appearance was not verified, there being observed only the existence of obliterating productive endoarteritis. The AA. consider the kidney changes in their case as resulting from the slow and prolongated action of the snake venom on the renal structures, on the strength of the following facts already known and agreed to: elimination of snake venom through the kidneys; capability of the same venom of determining diffused glomerulonephritis, and action of snake venom on vascular endothelium, turned essentially easier by the specific function of the organ. The modifications of metabolism were shown by urine and blood changes. Urine was eliminated in very small quantities (50 cc. in 24 hours; yet, absolute anuria was not observed. Hyaline and granular casts, as well as white blood cells and kidney cells along with albuminuria, were present. Hematologic examination revealed 11% of hemoglobin; 960.000 red blood cells per cmm., and 5.200 leukocytes per cmm.; differential blood count revealed increase of neutrophil leukocytes