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Sample records for early diabetic nephropathy

  1. Diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, Peter

    2006-01-01

    Diabetic nephropathy has become a worldwide epidemic, accounting for approximately one third of all cases of end-stage renal disease. With increasing prevalence of diabetes particularly in Asia, and a global prevalence of microalbuminuria of 39%, the problem is expected to grow. Improved management...... of diabetes aimed at improved glycemic control, to avoid initiation of diabetic nephropathy, and antihypertensive treatment blocking the renin-angiotensin system, to avoid its progression, need to be implemented, particularly in high-risk patients....

  2. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

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    Alejandra Guillermina Miranda-Díaz

    2016-01-01

    Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

  3. 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.

  4. Features of endothelial dysfunction in early diabetic nephropathy

    DEFF Research Database (Denmark)

    Jensen, T; Bjerre-Knudsen, J; Feldt-Rasmussen, B

    1989-01-01

    ); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls. The rise in tPA antigen with exercise was similar in the controls.......01) and II (difference not significant, p = 0.06) than in group I and normal controls. These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage. It is not yet clear whether these changes......The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h...

  5. Current Challenges in Diabetic Nephropathy: Early Diagnosis and Ways to Improve Outcomes

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    Sang Soo Kim

    2016-06-01

    Full Text Available Diabetes is often associated with chronic kidney disease (CKD and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.

  6. Hypertension in diabetes as related to nephropathy. Early blood pressure changes

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Borch-Johnsen, K; Mathiesen, E R

    1985-01-01

    and elevated urinary albumin excretion rate 20 to 200 micrograms/min; and group 3, patients with Albustix-positive urine at the time of diagnosis of diabetic nephropathy, that is, proteinuria greater than 0.5 g/24 hr on four consecutive visits with an interval of more than 1 month. We also studied blood...... that arterial hypertension is an early feature in the developing of diabetic nephropathy, with blood pressure rising before the presence of clinical proteinuria....

  7. Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review

    Science.gov (United States)

    Zhang, Lei; Mao, Wei; Guo, Xinfeng; Wu, Yifan; Li, Chuang; Lu, Zhaoyu; Su, Guobin; Li, Xiaoyan; Liu, Zhuangzhu; Guo, Rong; Jie, Xina; Wen, Zehuai; Liu, Xusheng

    2013-01-01

    Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence. PMID:23533513

  8. Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2013-01-01

    Full Text Available Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER, fasting blood glucose (FBG, serum creatinine (SCR, and blood urea nitrogen (BUN. The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence.

  9. Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    2000-01-01

    OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect...... and mortality of parents of 163 type 1 diabetic patients with nephropathy and parents of 163 sex- and age-matched normoalbuminuric patients with type 1 diabetes. RESULTS: Kaplan-Meier curves showed that total parental mortality was significantly increased in parents of type 1 diabetic patients with nephropathy...... (121 of 244 [ approximately 50%] ) as compared with parents of normoalbuminuric type 1 diabetic patients (119 of 269 [approximately 44%]) (P = 0.008 [log-rank test]) partially due to an increase in cardiovascular deaths (48 of 244 [approximately 20%] vs. 42 of 269 [approximately 16%], P

  10. Genetics of diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    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. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis of d...

  11. Urotensin-II level and its association with oxidative stress in early diabetic nephropathy.

    Science.gov (United States)

    Tabur, Suzan; Korkmaz, Hakan; Eren, Mehmet Ali; Oğuz, Elif; Sabuncu, Tevfik; Aksoy, Nurten

    2015-01-01

    Diabetic nephropathy is the most common cause of end stage renal failure. Early treatment of diabetic nephropathy depends on understanding the underlying mechanisms of the disease. In this study we investigated the role of U-II in early nephropathy and ıts association with oxidative stress, paraoxonase (PON)-1 and arylesterase. Twenty-three diabetic patients with microalbuminuria, 23 diabetic patients with normoalbuminuria and 25 healthy individuals were enrolled in the study. Serum total antioxidant status (TAS), total oxidant status (TOS), PON-1, arylesterase, and urotensin-II (U-II) levels were measured. Oxidative stress index (OSI) percent ratio of TOS to TAS level was accepted as OSI. Serum U-II levels were higher in the microalbuminuric diabetes group compared to the normoalbuminuric diabetic group and the healthy control group (p=0.009 and p=0.0001, respectively). Normoalbuminuric diabetic group's U-II levels were significantly higher compared to those of the healthy control group (p=0.0001). Correlation analysis yielded that plasma U-II levels are negatively correlated to TAS, arylesterase, and PON-1 levels (r=-0.395, p=0.001; r=-0.291, p=0.014; and r=-0.279, p=0.018, respectively) and that they had a positive correlation with OSI levels (r=0.312, p=0.008). These associations were confirmed in the multiple regression analysis. The results of multiple logistic regression analysis showed that oxidative stress is important in the development of microalbuminuria. The data of this study reveal that increased serum U-II has a role in the development of diabetic nephropathy. This effect of U-II may be related to high levels oxidative stress parameters. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus.

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    Kevin M Wheelock

    preservation of glomerular structures, suggesting that elevations of these kinin concentrations may reflect adaptive responses to early renal structural changes in diabetic nephropathy.

  13. Diabetic nephropathy and inflammation

    OpenAIRE

    Duran-Salgado, Montserrat B; Rubio-Guerra, Alberto F

    2014-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal failure worldwide. Besides, diabetic nephropathy is associated with cardiovascular disease, and increases mortality of diabetic patients. Several factors are involved in the pathophysiology of DN, including metabolic and hemodynamic alterations, oxidative stress, and activation of the renin-angiotensin system. In recent years, new pathways involved in the development and progression of diabetic kidney disease have been elucidat...

  14. Inflammation in Diabetic Nephropathy

    OpenAIRE

    Lim, Andy K. H.; Tesch, Gregory H.

    2012-01-01

    Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly i...

  15. URINE miRNAs: POTENTIAL BIOMARKERS FOR MONITORING PROGRESION OF EARLY STAGES OF DIABETIC NEPHROPATHY

    Science.gov (United States)

    Yang, Yeyi; Xiao, Li; Li, Jun; Kanwar, Yashpal S.; Liu, Fuyou; Sun, Lin

    2013-01-01

    With a steep increase in the incidence of type 1 and 2 diabetes globally, diabetic nephropathy (DN) has now become the leading cause of renal failure in the world. There are no suitable biomarkers for the diagnosis of early stages of DN. In recent years, tremendous efforts are being made worldwide to delineate the role of micro RNAs in the pathogenesis of DN. Circulating miRNAs in serum, plasma, urine and other body fluids, which reflect a response to various pathophysiological stresses, are being investigated in the context of diabetic nephropathy. Delineation of the changes in miRNA levels in patients with DN may lead to a better understanding of the progression of the disease. We present here an exhaustive survey of the miRNA literature, highlighting various studies performed over the last decade. The aim is to assess if changes in various miRNAs could correlate with the progression of diabetic nephropathy. Based on the survey, we found that miRNA-377, miRNA-192, miRNA-216/217 and miRNA-144 are increased in body fluids of patients with DN, while miRNA-21 and miRNA-375 are decreased. Overall, there are a very few miRNAs that are kidney specific, and although significant differences were observed in the urinary excretion of certain miRNAs, they were not correlative to their levels in the blood or plasma. Thus, it is completely plausible that urine-specific miRNAs could serve as novel biomarkers for the diagnosis of early stages of diabetic nephropathy. PMID:23683774

  16. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

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    Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

    2010-03-01

    The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg. (c) Georg Thieme Verlag KG Stuttgart . New York.

  17. Inflammation in Diabetic Nephropathy

    Science.gov (United States)

    Lim, Andy K. H.; Tesch, Gregory H.

    2012-01-01

    Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies. PMID:22969168

  18. Inflammation in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Andy K. H. Lim

    2012-01-01

    Full Text Available Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies.

  19. Early diagnostics and incidence of diabetic nephropathy depending on type 1 diabetes mellitus duration

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    V.A. Maslianko

    2017-03-01

    Full Text Available The objective — to establish the incidence of diabetic nephropathy (DN depending on duration of type 1 diabetes mellitus (DM, and also the content of cystatin С as a marker of early kidney damage. Materials and methods. Twenty eight patients with type 1 DM were enrolled in prospective study (11 men and 17 women aged 34.8 ± 7.2 years. Clinical and functional examination included the standard evaluation of renal function, and also the study of serum level of cystatin С. Results. In 17 out of 28 patients, the indexes of glomerular filtration rate calculated using the formulas of CKD-ЕРIcreat and CKD-ЕРIcys, indicated the different stages of chronic kidneys disease. Conclusions. Determination of cystatin C level and calculation of glomerular filtration rate using this index allows diagnosing the preclinical stages of kidney dysfunction in patients with type 1 DM in the normal creatinine level in the blood and without decline in glomerular filtration rate calculated using creatinine value. According to a retrospective study, the incidence and severity of DN in patients with type 1 DM increases with disease duration of more than 10 years.

  20. Protective effect of turnip root ethanolic extract on early diabetic nephropathy in the rats

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    Bahram Amouoghli-Tabrizi

    2011-11-01

    Full Text Available Background: Diabetes mellitus is a metabolic disorder and one of its most important consequences is renal insufficiency. A multitude of herbs has been described for the treatment of diabetes mellitus. The aim of present study was to assess the protective effect of turnip root ethanolic extract (TREE on early nephropathy in alloxan-induced diabetic rats.Materials and Method: Eighty male Wistar rats were randomly allocated into 4 equal groups including: healthy rats, normal healthy rats receiving TREE, diabetic rats and diabetic rats receiving TREE. Diabetes was induced by a single injection of alloxan (120 mg/kg; i.p. The extract (200 mg/kg was gavaged to TREE treatment groups daily for 8 weeks. At the end of experiment; serum levels of urea, uric acid and creatinine were assessed. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS, and activities of superoxide dismutase, catalase and glutathione peroxidase were measured in the renal tissue. Finally, the biochemical findings were matched with histopathological verification. Statistically, the quantitative data obtained, compared among the groups by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p<0.05.Results: In the diabetic rats, TREE significantly decreased the levels of serum biomarkers of renal injury. Furthermore, TREE significantly decreased the lipid peroxidation and elevated the decreased levels of antioxidant enzymes in diabetic rats. Histopathological findings were in agreement with the biochemical findings.Conclusion: TREE has protective effect on early diabetic nephropathy in the rats with experimentally induced diabetes

  1. Preventing diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Lund, S S; Rossing, P

    2001-01-01

    was to audit the effect of angiotensin converting enzyme (ACE) inhibition on the progression of microalbuminuria and development of diabetic nephropathy. We consecutively identified 227 type 1 diabetic patients with persistent microalbuminuria (urinary AER between 30 and 300mg/24h, ELISA). According...... to the level (> or = 100 or 6% or international guidelines, all patients at high-risk were....... Glycaemic control and blood pressure remained unchanged during the study. The implementation of modified international guidelines regarding the use of ACE inhibition in the treatment of microalbuminuric type 1 diabetic patients reduced progression to diabetic nephropathy comparable to what has previously...

  2. Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

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    Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge Fernando

    2017-11-29

    Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular versus glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury, albuminuria, and displayed low renal levels of megalin that were similar to that observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria, and increased renal megalin expression compared to diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  3. 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...

  4. Effect of ethanol extract of Rhodiola rosea on the early nephropathy in type 2 diabetic rats.

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    Wang, Zhi-sen; Gao, Fei; Lu, Fu-er

    2013-06-01

    This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.

  5. Clinical impact of albuminuria in diabetic nephropathy.

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

    2012-02-01

    Patients suffering from diabetic nephropathy, resulting in end-stage renal failure, are increasing in number. The pathophysiology of diabetic nephropathy remains to be fully investigated. In the clinical setting, the presence of albuminuria/overt proteinuria and a low glomerular filtration rate may predict poor renal prognosis, but the prognosis of the normoalbuminuric renally insufficient diabetic patient remains controversial. In addition to the measurement of urinary albumin excretion, biomarker studies to detect diabetic nephropathy more specifically at the early stage have been performed worldwide. There is a growing body of evidence for remission and/or regression of diabetic nephropathy, which may be an indicator for cardiovascular and renal risk reduction. Deeper insights into the pathological characteristics as well as the clinical impact of albuminuria on renal and cardiovascular outcome are required.

  6. Improved prognosis in type 1 diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Astrup, Anne Sofie; Tarnow, Lise; Rossing, Peter

    2005-01-01

    BACKGROUND: In early studies, a median survival time of 5 to 7 years from onset of diabetic nephropathy was observed. Furthermore, end-stage renal disease (ESRD) was the main cause of death. We prospectively assessed the impact of reno- and cardiovascular protective treatment on prognosis in type 1...... diabetic patients with diabetic nephropathy. METHODS: We prospectively followed 199 type 1 diabetic patients with diabetic nephropathy and 192 patients with normoalbuminuria for 10 years. Aggressive antihypertensive treatment was initiated in patients with diabetic nephropathy in mid 1980s, whereas statins......%) died; hereof, 25 deaths (42%) were ascribed to cardiovascular causes while 30 patients (50%) with nephropathy died with ESRD. The estimate of median survival time from onset of diabetic nephropathy was 21.7 years, SE 3.3 years. CONCLUSION: The survival of patients with diabetic nephropathy has improved...

  7. Diabetic nephropathy : pathology, genetics and carnosine metabolism

    NARCIS (Netherlands)

    Mooyaart, Antien Leonora

    2011-01-01

    My thesis concerns different aspects of diabetic nephropathy. A pathologic classification of diabetic nephropathy is developed, a meta-analyis of genes in diabetic nephropathy is developed and the other chapters are about the CNDP1 gene in relation to kidney disease, mainly diabetic nephropathy.

  8. Effect of calcium dobesilate combined with irbesartan therapy on proteinuria and serum inflammatory mediator levels in early diabetic nephropathy

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    Jing Hou

    2016-09-01

    Full Text Available Objective: To analyze the effect of calcium dobesilate combined with irbesartan therapy on proteinuria and serum inflammatory mediator levels in early diabetic nephropathy. Methods: A total of 74 patients with early diabetic nephropathy who received inpatient treatment in our hospital from July 2013 to July 2015 were included in the study and divided into observation group and control group (n=37 according to random number table. Control group received routine therapy, observation group received additional calcium dobesilate combined with irbesartan therapy, and then differences in proteinuria, hemorheology, renal blood flow parameters, serum inflammatory mediator levels and so on were compared between two groups. Results: Urine microalbumin, UAER value, whole blood viscosity, plasma viscosity, fibrinogen and Hct levels of observation group after treatment were lower than those of control group; color Doppler Vs max and Vd min values of observation group after treatment were higher than those of control group while PI and RI values were lower than those of control group; sICAM-1, MCP-1 and NLR values of observation group after treatment were lower than those of control group. Conclusion: Calcium dobesilate combined with irbesartan therapy can significantly inhibit the progression of early diabetic nephropathy and improve renal blood supply, and it has positive clinical significance.

  9. Relationship between Oxidant/Antioxidant Markers and Severity of Microalbuminuria in the Early Stage of Nephropathy in Type 2 Diabetic Patients

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    Ning Shao

    2013-01-01

    Full Text Available A wide range of microalbuminuria cutoff values are currently used for diagnosing the early stage of nephropathy in type 2 diabetes (T2D. This study analyzed the relationships between oxidant and antioxidant markers of nephropathy and the severity of microalbuminuria. The study included 50 healthy controls (Group 1, 50 diabetic patients with no nephropathy (Group 2, 50 diabetic patients with nephropathy and a urinary albumin excretion (UAE of 30–200 mg/24 h (Group 3, and 50 diabetic patients with UAE 200–300 mg/24 h (Group 4. Serum nitrotyrosine, conjugated dienes, 8-hydroxy-2′-deoxyguanosine (8-OHdG, superoxide dismutase (SOD, and total antioxidant capacity (T-AOC levels were determined. Oxidative stress is increased in the early stage of nephropathy in patients with T2D. There was a significant correlation between the extent of microalbuminuria and markers of oxidative stress. Multiple linear regression analysis identified lipid oxidative stress as a possible independent marker for evaluating the degree of renal damage in diabetic nephropathy. Stratifying microalbuminuria values during the early stage of nephropathy might be an important factor in facilitating earlier and more specific interventions.

  10. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

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    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

  12. Assessment of the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Hai-Xia Li

    2017-05-01

    Full Text Available Objective: To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy. Methods: 90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45 according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes. Results: Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05. After 3 months of treatment, creatinine (Scr, cystatin C (CysC, β2 microglobulin (β2-MG, N-acetyl-β-D-glucosaminidase (NAG, reactive oxygen species (ROS, advanced protein oxidation products (AOPPs, interleukin-8 (IL-8, interleukin-27 (IL-27 and procalcitonin (PCT levels of observation group were lower than those of control group while catalase (CAT, total superoxide dismutase (TSOD, interleukin-4 (IL-4, interleukin-10 (IL-10 and interleukin-13 (IL-13 levels were higher than those of control group (P<0.05. Conclusions: Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.

  13. Diabetic Nephropathy in Women With Preexisting Diabetes

    DEFF Research Database (Denmark)

    Ringholm, Lene; Damm, Julie Agner; Vestgaard, Marianne

    2016-01-01

    In women with preexisting diabetes and nephropathy or microalbuminuria, it is important to deliver careful preconception counselling to assess the risk for the mother and the foetus, for optimizing glycaemic status and to adjust medical treatment. If serum creatinine is normal in early pregnancy......, kidney function is often preserved during pregnancy, but complications such as severe preeclampsia and preterm delivery are still common. Perinatal mortality is now comparable with that in women with diabetes and normal kidney function. Besides strict glycaemic control before and during pregnancy, early...... and intensive antihypertensive treatment is important to optimize pregnancy outcomes. Methyldopa, labetalol, nifedipine and diltiazem are considered safe, whereas angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers should be stopped before or at confirmation of pregnancy...

  14. 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.

  15. Pharmacologic management of diabetic nephropathy.

    Science.gov (United States)

    Vivian, Eva M; Rubinstein, Gail Breen

    2002-11-01

    Diabetes mellitus and hypertension are leading causes of end stage renal disease in the United States. Drug therapy that focuses on tight glycemic control and blood pressure control reduces the progression of nephropathy and cardiovascular complications. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the progression of renal disease in patients with diabetes. The angiotensin II receptor blockers (ARBs) losartan and irbesartan have also been shown to reduce microalbuminuria compared with placebo. The nondihydropyridine calcium channel blockers (CCBs) verapamil and diltiazem have been shown to be as effective as an ACE inhibitor in reducing urinary albumin excretion. This paper reviews the pathophysiology and diagnosis of diabetic nephropathy and recent clinical trials assessing the most appropriate therapeutic options for delaying the progression of nephropathy in patients with diabetes. Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to August 2002) and the bibliographies of identified articles were reviewed. English-language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, and ARBs. Studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Patients with type 1 diabetes mellitus and evidence of nephropathy should be started on an ACE inhibitor unless contraindicated. The ARBs and ACE inhibitors are viable choices for patients with type 2 diabetes mellitus and evidence of proteinuria. Patients who experience adverse events such as dry cough with ACE inhibitors can be switched to ARBs. Clinical literature suggests that if monotherapy with an ACE inhibitor or ARB does not provide an

  16. Comparative analysis of diabetic nephropathy and non-diabetic nephropathy disease

    Directory of Open Access Journals (Sweden)

    Qiuxiang Chen

    2017-12-01

    Conclusion: Treatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.

  17. Fractalkine in type 2 Egyptian diabetics with and without nephropathy

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    Ebtissam Zakaria

    2013-01-01

    Results and Conclusion Our study showed that the serum fractalkine concentration was significantly elevated in type 2 diabetic patients with nephropathy (1153.14±261.1 compared with type 2 diabetic patients without nephropathy (705.78±150.59 and the control group (251.5±64 (both P=0.000. There was a significant correlation between serum fractalkine level and 24-h UAE, HBA1C, and serum creatinine. Thus, this positive correlation between serum fractalkine level and UAE could be an early predictor of microvascular complications in diabetic patients. We can conclude that serum fractalkine plays a pathogenic role in the development of diabetic nephropathy.

  18. Pregnancy and progression of diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, K; Jacobsen, P; Hommel, E

    2002-01-01

    as control subjects (group B). All patients received aggressive antihypertensive treatment (blood pressure goal diabetic nephropathy regarding blood pressure, albuminuria, s-cholesterol, smoking, retinopathy and s-creatinine (mean 79(SD 23......AIMS/HYPOTHESIS: Pregnancy could damage kidney function in diabetic nephropathy. We investigated the long-term impact of pregnancy on the progression of diabetic nephropathy. METHODS: Our observational follow-up study included all women patients with Type I (insulin-dependent) diabetes mellitus who...... developed diabetic nephropathy between 1970 and 1989 at Steno Diabetes Center (n = 93). Follow-up lasted 16 years (range 3-28) from the onset of diabetic nephropathy until death or the year 2000. A total of 26 women became pregnant after the onset of diabetic nephropathy (group A). The remaining 67 served...

  19. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY)

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma

    2016-01-01

    INTRODUCTION: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment...

  20. Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy

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    Tarek Kamal Abouzed

    2016-01-01

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

  1. Diabetic nephropathy – complications and treatment

    Science.gov (United States)

    Lim, Andy KH

    2014-01-01

    Diabetic nephropathy is a significant cause of chronic kidney disease and end-stage renal failure globally. Much research has been conducted in both basic science and clinical therapeutics, which has enhanced understanding of the pathophysiology of diabetic nephropathy and expanded the potential therapies available. This review will examine the current concepts of diabetic nephropathy management in the context of some of the basic science and pathophysiology aspects relevant to the approaches taken in novel, investigative treatment strategies. PMID:25342915

  2. Fish oil in diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, P; Hansen, B V; Nielsen, F S

    1996-01-01

    OBJECTIVE: Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids (fish oil) may have beneficial effects on albuminuria, kidney function, arterial blood pressure, and dyslipidemia. Therefore, we evaluated the long-term effect of fish...... oil in diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized controlled study comparing fish oil (4.6 g n-3 fatty acids/day) with placebo (olive oil) was performed in an outpatient clinic in a tertiary referral center. Thirty-six normotensive IDDM patients with diabetic...... nephropathy were included; 18 were treated with fish oil. Seven patients dropped out (four received fish oil), and results for the remaining 29 are presented. Albuminuria (enzyme immunoassay), glomerular filtration rate (51Cr-labeled EDTA plasma clearance), 24-h ambulatory blood pressure, and lipid profile...

  3. Update on Diabetic Nephropathy: Core Curriculum 2018.

    Science.gov (United States)

    Umanath, Kausik; Lewis, Julia B

    2018-02-02

    Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A 1c concentration diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Comprehensive approach to diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Bancha Satirapoj

    2014-09-01

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

  5. 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

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

  6. Markers of Diabetic Nephropathy in Diabetic Patients in Gusau ...

    African Journals Online (AJOL)

    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. The markers of diabetics nephropathy in diabetic patients, serum glucose, creatinine clearance, urinary albumin and ...

  7. Markers of Diabetic Nephropathy in Diabetic Patients in Gusau ...

    African Journals Online (AJOL)

    ABSTRACT: 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. The markers of diabetics nephropathy in diabetic patients, serum glucose, creatinine clearance, urinary ...

  8. Epigenetic modifications and diabetic nephropathy

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    Marpadga A. Reddy

    2012-09-01

    Full Text Available Diabetic nephropathy (DN is a major complication associated with both type 1 and type 2 diabetes, and a leading cause of end-stage renal disease. Conventional therapeutic strategies are not fully efficacious in the treatment of DN, suggesting an incomplete understanding of the gene regulation mechanisms involved in its pathogenesis. Furthermore, evidence from clinical trials has demonstrated a “metabolic memory” of prior exposure to hyperglycemia that continues to persist despite subsequent glycemic control. This remains a major challenge in the treatment of DN and other vascular complications. Epigenetic mechanisms such as DNA methylation, nucleosomal histone modifications, and noncoding RNAs control gene expression through regulation of chromatin structure and function and post-transcriptional mechanisms without altering the underlying DNA sequence. Emerging evidence indicates that multiple factors involved in the etiology of diabetes can alter epigenetic mechanisms and regulate the susceptibility to diabetes complications. Recent studies have demonstrated the involvement of histone lysine methylation in the regulation of key fibrotic and inflammatory genes related to diabetes complications including DN. Interestingly, histone lysine methylation persisted in vascular cells even after withdrawal from the diabetic milieu, demonstrating a potential role of epigenetic modifications in metabolic memory. Rapid advances in high-throughput technologies in the fields of genomics and epigenomics can lead to the identification of genome-wide alterations in key epigenetic modifications in vascular and renal cells in diabetes. Altogether, these findings can lead to the identification of potential predictive biomarkers and development of novel epigenetic therapies for diabetes and its associated complications.

  9. Disparate phospho-Smad2 levels in advanced type 2 diabetes patients with diabetic nephropathy and early experimental db/db mouse model

    DEFF Research Database (Denmark)

    Thomsen, Lise Høj; Fog-Tonnesen, Morten; Nielsen Fink, Lisbeth

    2017-01-01

    Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidn...

  10. Diabetic nephropathy – complications and treatment

    Directory of Open Access Journals (Sweden)

    Lim AK

    2014-10-01

    Full Text Available Andy KH Lim1–3 1Department of Nephrology, Monash Medical Center, Monash Health, 2Department of General Medicine, Dandenong Hospital, Monash Health, 3Department of Medicine, Monash University, Clayton, VIC, Australia Abstract: Diabetic nephropathy is a significant cause of chronic kidney disease and end-stage renal failure globally. Much research has been conducted in both basic science and clinical therapeutics, which has enhanced understanding of the pathophysiology of diabetic nephropathy and expanded the potential therapies available. This review will examine the current concepts of diabetic nephropathy management in the context of some of the basic science and pathophysiology aspects relevant to the approaches taken in novel, investigative treatment strategies. Keywords: diabetes, diabetic nephropathy, albuminuria, kidney disease, inflammation

  11. Prevalence of microalbuminuria and risk factor analysis in type 2 diabetes patients in Albania: the need for accurate and early diagnosis of diabetic nephropathy.

    Science.gov (United States)

    Pasko, N; Toti, F; Strakosha, A; Thengjilli, E; Shehu, A; Dedej, T; Ylli, A; Thereska, N

    2013-10-01

    Microalbuminuria is often the first sign of renal dysfunction in diabetes. This study aimed to investigate the prevalence of microalbuminuria in Albanian type 2 diabetes patients and its association with other cardiovascular risk factors. Three hundred and twenty-one patients with type 2 diabetes attending, diabetes centers in Albania were enrolled in this cross-sectional, multicenter study. The subjects, aged 40-70 years, had no known proteinuria or other kidney disease. Pregnant women and patients with acute infections were excluded. Data including waist circumference, duration of diabetes and history of hypertension were obtained by questionnaire. Blood samples were drawn after 12 h overnight fasting to measure glycosylated hemoglobin (HbA1c), serum cholesterol, triglyceride and creatinine. Microalbuminuria was assessed using dipstick kits in early morning urine samples. The prevalence of normoalbuminuria was 56.3%, microalbuminuria 40.8% and macroalbuminuria 2.8%. Systolic and diastolic blood pressure (pdiabetes (OR: 2.785, 95% CI: 1.156-3.759), systolic blood pressure (OR: 2.88, 95% CI: 1.85-6.85) and waist circumference (OR: 2.15, 95% CI: 1.01-5.45) in males and poor glycemic control (OR: 4.51, 95% CI: 1.45-13.98), duration of diabetes (OR: 2.568, 95% CI: 1.702-3.778) and waist circumference (OR: 4.87, 95% CI: 1.80-13.11) in females. The high proportion of type 2 diabetes patients with microalbuminuria raises implications for health policy in Albania. Screening programs and optimized control of modifiable risk factors are needed to reduce the risk of diabetic nephropathy.

  12. [Protective effect of calcium dobesilate against early diabetic nephropathy of rat kidney].

    Science.gov (United States)

    Gao, Mei-Juan; Liu, Ming; Li, Bo; Li, Ming-Long; Bian, Li-Xiang; Yu, Gui-Na

    2009-02-01

    The aim of this study is to study the effect of calcium dobesilate on streptozotocin (STZ)-induced early diabetic nephrophathy (DN) in rats. All male Wistar rats were randomly divided into six groups: normal group; DN blank group; calcium dobesilate 75, 150, and 300 mg x kg(-1) groups and perindopril 0.4 mg x kg(-1) group. Blood glucose and the 24 h urinary albumin were measured dynamically during the experiment, after 8 weeks administration, the level of glycosylated hemoglobin (HbA1c) was determined, the expressions of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloprotein-9 (MMP-9) in cortex of kidney were examined with immunohistochemical staining. The endothelin (ET) in plasma and kidney cortex was measured with radioimmunoassay, renal pathomorphism was observed with light and electron microscopes. Calcium dobesilate could decrease the 24 h urinary albumin and ET in plasma and kidney cortex, down-regulate the expression of PAI-1, and up-regulate MMP-9 in kidney. These findings suggested that calcium dobesilate could protect blood vessel endothelium, inhibit kidney fibrous degeneration, ameliorate renal pathological damage, and protect kidney function in many ways.

  13. New and old markers of progression of diabetic nephropathy.

    Science.gov (United States)

    Jerums, G; Premaratne, E; Panagiotopoulos, S; Clarke, S; Power, D A; MacIsaac, R J

    2008-11-13

    The onset of diabetic nephropathy is characterised by a rise in albumin excretion rate (AER) and/or a transient rise in glomerular filtration rate (GFR) (hyperfiltration). Without intervention AER increases exponentially and there is a linear decrease in GFR after onset of overt nephropathy. In overt nephropathy, AER is a predictor of decline in GFR and the early AER response to antihypertensive therapy correlates with long-term decline in GFR. AER can be measured by immunoassay or by other techniques including HPLC. However, HPLC assays result in higher levels of AER in normal subjects compared with immunoassayable AER. Recent data suggest that there are distinct albuminuric and non-albuminuric pathways to renal impairment in type 1 and type 2 diabetes. In type 2 diabetes, the non-albuminuric pathway may explain a decline in GFR to 60 ml/min/1.73 m(2) (CKD stages 1 and 2). Other potential markers of progression of diabetic nephropathy include transforming growth factor beta (TGFbeta) and connective tissue growth factor (CTGF). However, long-term studies are needed to define their roles as markers of progression. Diabetic nephropathy is likely to be more susceptible to intervention at an early stage and accurate estimation of GFR is already possible with cystatin C. However, improved formulas for estimating GFR based on using creatinine or other markers are still required, because this may still provide the most cost effective approach applicable to existing clinical practice.

  14. Adaptive changes in renal mitochondrial redox status in diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu

    2012-01-15

    Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter.

  15. Diabetic nephropathy among Mexican Americans.

    Science.gov (United States)

    Debnath, Subrata; Thameem, Farook; Alves, Tahira; Nolen, Jacqueline; Al-Shahrouri, Hania; Bansal, Shweta; Abboud, Hanna E; Fanti, Paolo

    2012-04-01

    The incidence of diabetic nephropathy (DN) is growing rapidly worldwide as a consequence of the rising prevalence of Type 2 diabetes mellitus (T2DM). Among U.S. ethnic groups, Mexican Americans have a disproportionately high incidence and prevalence of DN and associated end-stage renal disease (ESRD). In communities bordering Mexico, as many as 90% of Mexican American patients with ESRD also suffer from T2DM compared to only 50% of non-Hispanic Whites (NHW). Both socio-economic factors and genetic predisposition appear to have a strong influence on this association. In addition, certain pathogenetic and clinical features of T2DM and DN are different in Mexican Americans compared to NHW, raising questions as to whether the diagnostic and treatment strategies that are standard practice in the NHW patient population may not be applicable in Mexican Americans. This article reviews the epidemiology of DN in Mexican Americans, describes the pathophysiology and associated risk factors, and identifies gaps in our knowledge and understanding that needs to be addressed by future investigations.

  16. The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy.

    Science.gov (United States)

    Yu, Ruichao; Bo, Hong; Villani, Vincenzo; Spencer, Philip J; Fu, Ping

    2016-01-01

    There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n =6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of

  17. The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Ruichao Yu

    2016-02-01

    Full Text Available Background/Aims: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN. The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4 is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17 pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. Methods: Streptozotocin (STZ-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6; and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6 and a control group (Control, n =6. Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. Results: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. Conclusions: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through

  18. Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis.

    Science.gov (United States)

    Jerums, George; Panagiotopoulos, Sianna; Premaratne, Erosha; Power, David A; MacIsaac, Richard J

    2008-01-01

    In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 +/- 4.3 (T1), 10.5 +/- 5.4 (T2, normotensive) and 18.4 +/- 6.2 (T2, hypertensive) in early DN and 7.6 +/- 11.1 (T1) and 20.8 +/- 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 +/- 0.5 (T1), 1.6 +/- 0.5 (T2, normotensive) and 2.1 +/- 0.3 (T2, hypertensive) in early DN and 9.8 +/- 1.5 (T1) and 9.2 +/- 1.1 (T2) in late DN. AER and GFR responses in each treatment group were closely correlated in late nephropathy (T1, r = -0.67, p = 0.03; T2, r = 0.57, p = 0.02) but not in early nephropathy. In contrast to late DN, the initial decrease in AER with antihypertensive therapy was not shown to predict the subsequent rate of decline of GFR in early DN. It follows that assessment of renoprotection during antihypertensive therapy in early nephropathy should be based not only on albuminuria but also on the GFR response. Copyright 2008 S. Karger AG, Basel.

  19. Monitoring kidney function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, P; Astrup, A S; Smidt, U M

    1994-01-01

    Progression in diabetic nephropathy is usually determined by repeated measurements of glomerular filtration rate and expressed as rate of decline in glomerular filtration rate. Our aim was to evaluate the agreement between rate of decline in glomerular filtration rate estimated from the Cockroft......-Gault formula: (140-age)*K*body weight*(1/S-creatinine) and measured by the plasma clearance of 51Cr-EDTA. All insulin-dependent diabetic patients with diabetic nephropathy followed-up for at least 5 years with at least 5 simultaneous measurements of glomerular filtration rate, s-creatinine, and weight were...

  20. Cystatin-C and TGF-β levels in patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Mumtaz Takir

    2016-11-01

    Conclusions: Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.

  1. Diabetic nephropathy in Surinamese South Asian subjects

    NARCIS (Netherlands)

    Chandieshaw, Prataap Kalap; Chandie Shaw, Prataap Kalap

    2008-01-01

    This thesis focuses on the incidence and risk factors for nephropathy in diabetic and non-diabetic Surinamese South Asians. The Surinamese South Asians, originally descended from the North-East India. Due to the former colonial bounds with the Netherlands, a relatively

  2. Prevention of Diabetic Nephropathy | Saleh | Nigerian Medical ...

    African Journals Online (AJOL)

    A review of relevant literatures was conducted using available medical journals, MEDLINE and Science direct via the internet. Other websites were also visited to source for information. The key words employed were: diabetes mellitus, diabetic nephropathy and renal failure. This review was able to outline measures that ...

  3. Evaluation of Early Markers of Nephropathy in Patients with Type 2 Diabetes Mellitus

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    Pierina De Muro

    2016-01-01

    Full Text Available Aims. T2DM often remains undiagnosed for many years because hyperglycemia develops gradually and may not produce any symptoms. As patients with T2DM are at increased risk of microvascular and macrovascular complications, the preclinical diagnosis of the state is the key point of the disease management. Methods. We evaluated parameters such as GAGs/PGs, NAG, and NGAL in urine samples from 43 normoalbuminuric T2DM patients and 31 apparently healthy control subjects. Results. The total urinary GAG excretion showed no significant differences between patients and controls. The electrophoretic analysis evidenced the presence of UTI and its degradation products (LSC and SM-LSC, CS, and HS. We observed modifications of HS and total UTI (including UTI and its degradation products relative contents in T2DM patients compared with controls whereas no differences in CS percentage were found. NGAL levels were significantly increased in T2DM patients and were positively correlated with both NAG (r=0.606, p<0.0001 and the presence of hypertension (r=0.352, p<0.05. Conclusions. These data suggest that the assessed molecules could represent useful markers to detect early renal impairment in patients with T2DM.

  4. Hypothyroidism Complicating Nephropathy in a Diabetes Patient

    OpenAIRE

    Jayaprakash Sahoo; Ilangovan Veerappan; Anila Abraham; Somasundaram Hariharan

    2012-01-01

    We describe a patient with type 2 diabetes mellitus and autoimmune hypothyroidism who presented with elevated serum creatinine possibly due to subclinical rhabdomyolysis induced by hypolipidemic drug therapy in the background of diabetic nephropathy. Both hypothyroidism and rhabdomyolysis were asymptomatic in this case as evidenced by lack of classical clinical features of hypothyroidism despite elevated serum TSH and absent pigment cast in renal biopsy. The combination of diabetes mellitus a...

  5. Diabetic nephropathy: Time to withhold development and progression - A review

    Directory of Open Access Journals (Sweden)

    Usama A.A. Sharaf El Din

    2017-07-01

    Full Text Available The recent discoveries in the fields of pathogenesis and management of diabetic nephropathy have revolutionized the knowledge about this disease. Little was added to the management of diabetic nephropathy after the introduction of renin angiotensin system blockers. The ineffective role of the renin- angiotensin system blockers in primary prevention of diabetic nephropathy in type 1 diabetes mellitus necessitated the search for other early therapeutic interventions that target alternative pathogenic mechanisms. Among the different classes of oral hypoglycemic agents, recent studies highlighted the distinguished mechanisms of sodium glucose transporter 2 blockers and dipeptidyl peptidase-4 inhibitors that settle their renoprotective actions beyond the hypoglycemic effects. The introduction of antioxidant and anti-inflammatory agents to this field had also added wealth of knowledge. However, many of these agents are still waiting well-designed clinical studies in order to prove their beneficial therapeutic role. The aim of this review of literature is to highlight the recent advances in understanding the pathogenesis, diagnosis, the established and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.

  6. Pathophysiology of diabetic nephropathy: involvement of multifaceted signalling mechanism.

    Science.gov (United States)

    Balakumar, Pitchai; Arora, Mandeep Kumar; Reddy, Jayarami; Anand-Srivastava, Madhu B

    2009-08-01

    Diabetic nephropathy is a major cause of end-stage renal failure and the mortality rate due to this disease is continuously progressing worldwide. The multifaceted signalling mechanisms have been identified to be involved in the pathogenesis of diabetic nephropathy. Despite the modern therapies like antidiabetics, antihypertensives, and antioxidants available to treat diabetic nephropathy; most of patients continue to show progressive renal damage. It suggests that the key pathogenic mechanism involved in the induction and progression of diabetic nephropathy is still remaining active and unmodified by the present therapies. The purpose of this review is to bring together the current information concerning the signalling systems involved in the pathogenesis of diabetic nephropathy.

  7. Antioxidant treatment attenuates lactate production in diabetic nephropathy

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Nielsen, Per Mose; Stokholm Nørlinger, Thomas

    2017-01-01

    -of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2......-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels......The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying...

  8. Clinical and therapeutic aspects of diabetic nephropathy.

    Science.gov (United States)

    Strippoli, Giovanni F; Di Paolo, Salvatore; Cincione, Raffaele; Di Palma, Anna M; Teutonico, Annalisa; Grandaliano, Giuseppe; Schena, Francesco P; Gesualdo, Loreto

    2003-01-01

    The prognosis of renal survival in both type 1 and type 2 diabetes mellitus is not benign. Several factors characterize the increase in the risk of developing renal damage in diabetic patients, distinguished in diabetes-related factors, genetic factors and other factors. Diagnosis requires standard annual urinalysis and dipstick for albumin. In patients with negative urine dipstick, the routine approach is to evaluate the albumin/creatinine ratio (ACR) in the first voided urine. The degree of renal impairment is assessed by an annual evaluation of the glomerular filtration rate (GFR) by the Cockroft/Gault formula in normoalbuminuric patients. In patients with overt nephropathy this evaluation needs to be more frequent. A thorough therapeutic approach, in both the early and later stages of diabetic nephropathy, is fundamental because of the increased risk of morbidity and mortality. Renal damage (and the natural history of the disease) is approached on three different levels. Primary prevention, in patients with no clinical and biochemical signs of renal damage, is a strict glycemic control by oral antidiabetic agents or insulin, as required, together with the maintenance of blood pressure (BP) levels prevention aims to prevent or slow the progresssion from micro- to macroalbuminuria. BP control is the first-line approach, along with a strict glycemic control. At this stage, it is necessary to use other anti-hypertensive agents besides ACE-inhibitors to achieve optimal BP levels of 130/85 mmHg. Tertiary prevention addresses the reduction in the rate of renal failure progression by optimal BP control, a slightly hypoproteic diet and the control of dyslipidemia, in the presence of a (non-fundamental) euglycemic state. a pharmacological blockade of endothelin and/or sympathetic system, an amelioration of hypoxia by correcting reduced hemoglobin levels, an interference with the formation and accumulation of advanced glycosilation end-products (AGE). Finally, the

  9. Diabetic nephropathy in hemodialysis patients in casablanca.

    Science.gov (United States)

    Khanfri, N; Medkouri, G; Aghai, R; Hachim, K; Benghanem, M G; Ramdani, B; Zaid, D

    2005-01-01

    Diabetes is the main cause of end-stage renal disease (ESRD) in the developed countries and its prevalence and incidence have been constantly increasing over the years. To determine the prevalence and profile of diabetic nephropathy in our ESRD population, we retrospectively studied 564 hemodialysis patients in ten dialysis units in Casablanca. The mean age was 49 +/-16.2 years. The diabetic nephropathy came at the third rank with a prevalence of 13.5% behind chronic glomerulonephritis (21.8%) and hypertensive nephropathy (14.7%). Almost 74% of our diabetics were type 2. From the time of diagnosis the type 2 diabetics reached the ESRD earlier than the type 1 diabetics with a mean period of 15.1 +/- 7 years and 18.8 +/- 5 years, respectively; however, the difference was not statistically significant. There was at least another microangiopathic complication in 95.4% of the patients and macroangiopathic complication in 82%. The median hemoglobin A1C in all patients was higher than normal value. We conclude that ESRD is a serious complication of diabetes, which is constantly increasing. The appropriate management of diabetes and a multidisciplinary approach are necessary to avoid it or at least delay its occurrence.

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

    Directory of Open Access Journals (Sweden)

    Anubhav Thukral

    2011-01-01

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

  11. Diabetic nephropathy – complications and treatment

    OpenAIRE

    Lim AK

    2014-01-01

    Andy KH Lim1–3 1Department of Nephrology, Monash Medical Center, Monash Health, 2Department of General Medicine, Dandenong Hospital, Monash Health, 3Department of Medicine, Monash University, Clayton, VIC, Australia Abstract: Diabetic nephropathy is a significant cause of chronic kidney disease and end-stage renal failure globally. Much research has been conducted in both basic science and clinical therapeutics, which has enhanced understanding of the pathophysiology of diabetic ne...

  12. Protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Ling Zhang

    2017-06-01

    Full Text Available Objective: To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms. Methods: A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25 and control group (n=25. On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr and β-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group; renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group; TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group. Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it

  13. Improved prognosis of diabetic nephropathy in type 1 diabetes

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken L; Carstensen, Bendix

    2015-01-01

    The natural history of diabetic nephropathy offered an average survival of only 5-7 years. During the past decades, multiple changes in therapy and lifestyle have occurred. The prognosis of diabetic nephropathy after implementing stricter control of blood pressure (including increased use of long......-term renin-angiotensin system inhibition), lipids, and glycemia, along with less smoking and other lifestyle and treatment advancements, is inadequately analyzed. To clarify this, we studied 497 patients with type 1 diabetes and diabetic nephropathy at the Steno Diabetes Center and compared them...... previously 4.0 to 3.3 ml/min per 1.73 m2/year. During a median follow-up of 9.1 years, 29% of participants doubled their plasma creatinine or developed end-stage renal disease. Mortality risk was similar to our prior study (hazard ratio 1.05 (0.76-1.43). However, after age adjustment, as both diabetes...

  14. Hypothyroidism Complicating Nephropathy in a Diabetes Patient

    Directory of Open Access Journals (Sweden)

    Jayaprakash Sahoo

    2012-01-01

    Full Text Available We describe a patient with type 2 diabetes mellitus and autoimmune hypothyroidism who presented with elevated serum creatinine possibly due to subclinical rhabdomyolysis induced by hypolipidemic drug therapy in the background of diabetic nephropathy. Both hypothyroidism and rhabdomyolysis were asymptomatic in this case as evidenced by lack of classical clinical features of hypothyroidism despite elevated serum TSH and absent pigment cast in renal biopsy. The combination of diabetes mellitus and hypothyroidism is common in the general population and should not be forgotten in patients with diabetes and kidney disease.

  15. Plasma proteins production and excretion in diabetic nephropathy in ...

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    Plasma proteins,. Diabetic nephropathy,. Diabetes mellitus. ABSTRACT. Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality in both developed and developing countries. In type II diabetes patients with normoalbuminuria, fibrinogen production is increased, ...

  16. Diabetic Nephropathy : Evaluation with Doppler Ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Jung Suk; Kim, Seung Hyup; Kang, Heung Sik; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1996-06-15

    To compare Doppler ultrasonography with laboratory tests in evaluation of diabetic nephropathy. Fifty-five patients (mean age = 60, M : F = 26 : 29) with diabetes mellitus underwent renal Doppler ultrasonography. Resistive indices were compared with degree of proteinuria, serum creatinine level, and creatinine clearance rate. Eighteen patients who showed no proteinuria or microscopic proteinuria had a mean resistive index (RI) of 0.72 (SD, 0.05), 16 patients with macroscopic proteinuria without nephrotic syndrome had a mean RI of 0.82 (SD, 0.13), and 21 patients with nephrotic syndrome had a mean RI of 0.90 (SD, 0.12). Renal RI correlated highly with serum creatinine level (r = 0.62) and creatinine clearance rate (r = -0.43). Renal Doppler ultrasonography provides a useful indication of renal function in diabetic nephropathy but cannot offer an advantage over conventional laboratory test

  17. Advanced Glycation end Products, Oxidative Stress and Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Sho-ichi Yamagishi

    2010-01-01

    Full Text Available About 246 million people worldwide had diabetes in 2007. The global figure of people with diabetes is projected to increase to 370 million in 2030. As the prevalence of diabetes has risen to epidemic proportions worldwide, diabetic nephropathy has become one of the most challenging health problems. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory, and the number of diabetic patients on end-stage renal disease is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. There is accumulating evidence that advanced glycation end products (AGEs, senescent macroprotein derivatives formed at an accelerated rate under diabetes, play a role in diabetic nephropathy via oxidative stress generation. In this paper, we review the pathophysiological role of AGEs and their receptor (RAGE-oxidative stress system in diabetic nephropathy.

  18. CLINICAL GUIDELINE FOR THE TREATMENT OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    R. A. Nadeeva

    2015-01-01

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

  19. Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

    Science.gov (United States)

    Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hohino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi

    2017-10-27

    The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

  20. Pathological study of diabetic Nephropathy based on renal Biopsy ...

    African Journals Online (AJOL)

    Background of the Study, Aims & Objectives: There are few studies on the histological patterns of diabetic nephropathy in this environment on a prospective basis. This study is important because of the increasing prevalence of diabetes mellitus and diabetic nephropathy in this environment. The aim of this study was to show ...

  1. Diabetic nephropathy: new approaches for improving glycemic control and reducing risk.

    Science.gov (United States)

    Schernthaner, Guntram; Schernthaner, Gerit Holger

    2013-01-01

    Nephropathy is a common consequence of diabetes, with a high prevalence in patients with type 1 (15%-25%) and type 2 diabetes mellitus (T2DM; 30%-40%). Nephropathy is associated with a poor prognosis and high economic burden. The risk of developing nephropathy increases with the duration of diabetes, and early diagnosis and treatment of risk factors for nephropathy (e.g., tight control of glycemia and hypertension) can reduce the development and progression of diabetic nephropathy. Advances in our understanding of the mechanisms of renal complications associated with diabetes and the etiology of nephropathy have identified additional risk factors for nephropathy, and novel therapeutic options are being explored. This review discusses the pathophysiology of diabetic nephropathy and common risk factors. Furthermore, we discuss emerging treatments for T2DM that could potentially slow or prevent the progression of diabetic nephropathy. The use of incretin-based therapies, such as the dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, is growing in patients with T2DM, due to their efficacy and tolerability profiles. As renal safety is a key factor when choosing treatment options to manage patients with T2DM, drugs that are suitable for use in patients with varying degrees of renal impairment without a requirement for dose adjustment, such as the DPP-4 inhibitor linagliptin, are of particular use. The ongoing advances in T2DM therapy may allow optimization of glycemic control in a wide range of patients, thereby helping to reduce the increasing morbidity and mortality associated with diabetic nephropathy.

  2. Risk factors and management of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Mohamed Akheel Ahmed

    2013-01-01

    Full Text Available To determine the risk factors for nephropathy in diabetic patients and to study the management of diabetic nephropathy (DN, we conducted a hospital-based prospective study in the Internal Medicine department of our hospital on 60 patients with DN and 60 diabetic patients without DN. An odds ratio (OR disclosed the following risk factors: Hypertension (OR = 2.06, family history of diabetes (OR = 1.23, family history of DN (OR = 2.86, uncontrolled hyperglycemia (OR = 11.80, obesity (OR = 1.07, duration of diabetes between 11 and 20 years (OR = 4.69, smoking (OR = 2.79, alcohol consumption (OR = 3.75, other complications (OR = 2.03, lack of physical activity (OR = 1.51 and anemia (OR = 2.29. According to these risk factors, we suggest that improving patient′s knowledge on diabetes and its treatment, life style modifications and aggressive management of the disease may delay the progression of disease to advanced stages.

  3. Long-term prevention of diabetic nephropathy

    DEFF Research Database (Denmark)

    Schjoedt, K J; Hansen, H P; Tarnow, L

    2008-01-01

    . Glycaemic control and blood pressure remained nearly unchanged. CONCLUSIONS/INTERPRETATION: In our outpatient clinic, the implementation of RAAS-blocking treatment in type 1 diabetic patients with microalbuminuria successfully reduced long-term progression to overt DN to a rate similar to those previously......AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin......-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n=227...

  4. [Pathophysiology of diabetic nephropathy: a literature review].

    Science.gov (United States)

    Meza Letelier, Carlos Eduardo; San Martín Ojeda, Camilo Alfredo; Ruiz Provoste, José Javier; Frugone Zaror, Cristobal Jesus

    2017-01-12

    Chronic kidney disease is a common complication of diabetes. Its importance lies in its high prevalence and future projection. It is associated with high health costs and global cardiovascular deterioration as well. The development of this disease pathophysiology is being studied and it is known that a series of complex molecular pathways determining a microvascular disease are involved. This review addresses the known pathways in the development of diabetic nephropathy aiming to improve the understanding of potential therapeutic targets that could be developed in the future.

  5. Novel approaches in diabetic nephropathy

    NARCIS (Netherlands)

    Alkhalaf, Alaa

    2013-01-01

    Dit proefschrift laat zien dat het carnosinase-1 gen (CNDP1) voorspellend is voor het risico op eindstadium nierfalen bij patiënten met type 1 diabetes. In tegenstelling tot de bevindingen van cross-sectionele studies bij patiënten met type 2 diabetes, blijkt de homozygote variant voor het laagste

  6. Peroxisome Proliferator-Activated Receptors in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Shinji Kume

    2008-01-01

    Full Text Available Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of the renin-angiotensin system. This review summarizes data from clinical and experimental studies regarding the relationship between PPARs and diabetic nephropathy. The therapeutic potential of PPAR agonists in the treatment of diabetic nephropathy is also discussed.

  7. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial.

    Science.gov (United States)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

    2016-03-02

    Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws

  8. The Role of Autophagy in the Pathogenesis of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Kosuke Yamahara

    2013-01-01

    Full Text Available Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The multipronged drug approach targeting blood pressure and serum levels of glucose, insulin, and lipids fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to combat diabetic nephropathy is required. Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells and plays a critical role in maintaining cellular homeostasis. The accumulation of proteins and organelles damaged by hyperglycemia and other diabetes-related metabolic changes is highly associated with the development of diabetic nephropathy. Recent studies have suggested that autophagy activity is altered in both podocytes and proximal tubular cells under diabetic conditions. Autophagy activity is regulated by both nutrient state and intracellular stresses. Under diabetic conditions, an altered nutritional state due to nutrient excess may interfere with the autophagic response stimulated by intracellular stresses, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing the relationships between autophagy and diabetic nephropathy and suggest the therapeutic potential of autophagy in diabetic nephropathy.

  9. A SHORT-TERM EVALUATIVE STUDY OF DIABETIC NEPHROPATHY PATIENT

    Directory of Open Access Journals (Sweden)

    A Vaishya

    2012-10-01

    months of treatment and dietary care, edema/swelling, the major signs/symptoms of diabetic nephropathy that reduced significantly and moreover on an average one third reduction of all signs/symptoms among the cases may satisfy the cases resulting to better compliance to drug and dietary management. Better improvement in cases with higher GFR indicated that early detection of diabetic nephropathy cases is essential.

  10. Decrease in toe pinch force in male type 2 diabetic patients with diabetic nephropathy.

    Science.gov (United States)

    Kataoka, Hiroaki; Miyatake, Nobuyuki; Kitayama, Naomi; Murao, Satoshi; Tanaka, Satoshi

    2017-11-27

    The purpose of this cross-sectional study was to investigate the toe pinch force (TPF) of type 2 diabetic patients with diabetic nephropathy by disease stage, and to clarify the factors affecting the TPF. Seventy-four men with diabetic nephropathy (age: 62.7 ± 8.9 years, duration of diabetes: 14.2 ± 8.6 years) were enrolled. According to the staging of diabetic nephropathy, TPF and knee extension force (KEF) were compared among three groups: normoalbuminuria, microalbuminuria, and overt nephropathy. In addition, we investigated factors influencing TPF and KEF by performing multiple regression analysis. Normoalbuminuria group, microalbuminuria group, and overt nephropathy group included 26, 25, and 23 patients, respectively. The TPF of the overt nephropathy group (3.15 ± 0.75 kg) was significantly lower than that of the normoalbuminuria (4.2 ± 0.7 kg, p diabetic polyneuropathy (DPN) and diabetic nephropathy were determinant factors of the TPF; and age, body mass index, and diabetic nephropathy were determinant factors of the KEF. We found in male patients with diabetic nephropathy, the TPF and KEF decreased with progression of diabetic nephropathy. Furthermore, our findings suggest diabetic nephropathy and DPN are critically involved in the reduction of TPF and KEF.

  11. Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy

    DEFF Research Database (Denmark)

    Jacobsen, P; Rossing, K; Rossing, P

    1998-01-01

    The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early an...

  12. Role of Neuropilin-1 in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Tzvetanka Bondeva

    2015-06-01

    Full Text Available Diabetic nephropathy (DN often develops in patients suffering from type 1 or type 2 diabetes mellitus. DN is characterized by renal injury resulting in proteinuria. Neuropilin-1 (NRP-1 is a single-pass transmembrane receptor protein devoid of enzymatic activity. Its large extracellular tail is structured in several domains, thereby allowing the molecule to interact with multiple ligands linking NRP-1 to different pathways through its signaling co-receptors. NRP-1’s role in nervous system development, immunity, and more recently in cancer, has been extensively investigated. Although its relation to regulation of apoptosis and cytoskeleton organization of glomerular vascular endothelial cells was reported, its function in diabetes mellitus and the development of DN is less clear. Several lines of evidence demonstrate a reduced NRP-1 expression in glycated-BSA cultured differentiated podocytes as well as in glomeruli from db/db mice (a model of type 2 Diabetes and in diabetic patients diagnosed with DN. In vitro studies of podocytes implicated NRP-1 in the regulation of podocytes’ adhesion to extracellular matrix proteins, cytoskeleton reorganization, and apoptosis via not completely understood mechanisms. However, the exact role of NRP-1 during the onset of DN is not yet understood. This review intends to shed more light on NRP-1 and to present a link between NRP-1 and its signaling complexes in the development of DN.

  13. Sarcopenia in diabetic nephropathy: a cross-sectional study.

    Science.gov (United States)

    Çeliker, Meral; Selçuk, Mustafa Yavuz; Olt, Serdar

    2018-01-01

    To investigate the relationship between sarcopenia and diabetic nephropathy. 56 diabetic patients without complications, 50 diabetic patients with nephropathy, 53 healthy controls included in this present study. Demographic characteristics such as sex, age, anthropometric measurements such as weight, body mass index [BMI], hip circumference, waist circumference and upper arm circumference were measured. Sarcopenia diagnosis was based on European Working Group on Sarcopenia in Older People [EWGSOP] criteria which consist of hand grip strength, 6-meter walking test and muscle mass. The frequency of sarcopenia increased gradually from 15,1% in healthy control group to 21,4% in the diabetes group, and 34% in diabetic nephropathy group (X2 for trend, p=0.029),. The frequency of sarcopenia was similar in diabetes and diabetic nephropathy group. However, the frequency of sarcopenia was higher in diabetic nephropathy than healthy controls (OR=2.89, CI [1.11-7.51] in logistic regression). In the present study, the prevalence of sarcopenia was higher in patients with diabetic nephropathy compared to healty co`ntrols.

  14. Glycosylated hemoglobin as a forecast factor of progressing of diabetic nephropathy in patients with diabetes type 1

    Directory of Open Access Journals (Sweden)

    Pertseva N.O.

    2017-12-01

    Full Text Available The aim of the study was to propose a mathematical model for prediction of development of diabetic nephropathy in patients with diabetes mellitus by determining the level of glycosylated hemoglobin - as a factor in the development and progression of diabetic nephropathy. A survey of 136 patients with type 1 diabetes was performed in the endocrinology department of the OSH «Clinic of the Medical Academy», Dnipro in 2016-2017. Clinical laboratory examination included: determination of the level of glycosylated hemoglobin (HbA1c, level of blood creatinine, level of albuminuria. The GFR was calculated by the formula CKD-EPI. The obtained results of the study, using methods of correlation and regression analysis, show a clear correlation between the GFR score in patients with diabetes mellitus and the level of glycosylated hemoglobin. Statistical methods of analysis have shown that the level of glycosylated hemoglobin can be considered as an early predictor of development of diabetic nephropathy. The mathematical equation of prognosis for the onset of diabetic nephropathy can be used to determine the prognosis for the development of diabetic nephropathy in diabetes mellitus patients in clinical practice for the timely inclusion of patients with a high prognostic risk in a group requiring more stringent glycemic control.

  15. Reversal of Diabetic Nephropathy by a Ketogenic Diet

    Science.gov (United States)

    Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.

    2011-01-01

    Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091

  16. Reversal of diabetic nephropathy by a ketogenic diet.

    Directory of Open Access Journals (Sweden)

    Michal M Poplawski

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

  17. Histone Lysine Methylation in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Guang-dong Sun

    2014-01-01

    Full Text Available Diabetic nephropathy (DN belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

  18. Urinary semaphorin 3A correlates with diabetic proteinuria and mediates diabetic nephropathy and associated inflammation in mice

    NARCIS (Netherlands)

    Mohamed, Riyaz; Ranganathan, Punithavathi; Jayakumar, Calpurnia; Nauta, Ferdau L.; Gansevoort, Ron T.; Weintraub, Neal L.; Brands, Michael; Ramesh, Ganesan

    2014-01-01

    Semaphorin 3A (sema3A) was recently identified as an early diagnostic biomarker of acute kidney injury. However, its role as a biomarker and/or mediator of chronic kidney disease (CKD) related to diabetic nephropathy is unknown. We examined the expression of sema3A in diabetic animal models and in

  19. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) : Essential study design and rationale of a randomised clinical multicentre trial

    NARCIS (Netherlands)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

    2016-01-01

    Introduction Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in

  20. Cardiac autonomic neuropathy predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Astrup, Anne Sofie; Tarnow, Lise; Rossing, Peter

    2006-01-01

    Cardiac autonomic neuropathy (CAN) has been associated with a poor prognosis in patients with diabetes. Because CAN is common in patients with diabetic nephropathy, we evaluated the predictive value of CAN in type 1 diabetic patients with and without diabetic nephropathy....

  1. The role of the complement system in diabetic nephropathy.

    Science.gov (United States)

    Flyvbjerg, Allan

    2017-05-01

    The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and socioeconomic costs worldwide. One of the most serious consequences of diabetes mellitus is the development of diabetic angiopathy, which manifests clinically as microvascular and macrovascular complications. One microvascular complication, diabetic nephropathy, is the most common cause of end-stage renal disease in developed countries. Although several available therapeutic interventions can delay the onset and progression of diabetic nephropathy, morbidity associated with this disease remains high and new therapeutic approaches are needed. In addition, not all patients with diabetes mellitus will develop diabetic nephropathy and thus new biomarkers are needed to identify individuals who will develop this life-threatening disease. An increasing body of evidence points toward a role of the complement system in the pathogenesis of diabetic nephropathy. For example, circulating levels of mannose-binding lectin (MBL), a pattern recognition molecule of the innate immune system, have emerged as a robust biomarker for the development and progression of this disease, and evidence suggests that MBL, H-ficolin, complement component C3 and the membrane attack complex might contribute to renal injury in the hyperglycaemic mileu. New approaches to modulate the complement system might lead to the development of new agents to prevent or slow the progression of diabetic nephropathy.

  2. Current concepts in the management of diabetic nephropathy

    NARCIS (Netherlands)

    Waanders, F.; Visser, F. W.; Gans, R. O. B.

    2013-01-01

    Although much progress has been made in slowing the progression of diabetic nephropathy, renal dysfunction and development of end-stage renal disease (ESRD) remain major concerns in diabetes. In addition, diabetic patients with microalbuminuria have an increased cardiovascular mortality. Therefore,

  3. Transforming growth factor-β in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Karima Y. Ahmed

    2013-01-01

    Conclusion Serum TGF-β level increases in patients of both type 1 and type 2 diabetes and in those with diabetic nephropathy. TGF-β is considered one of the major mediators of diabetic renal fibrogenesis that Results in end-stage renal disease.

  4. Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Bălăşescu Elena

    2016-03-01

    Full Text Available Introduction. Diabetes Mellitus causes ultrastructural changes triggered by partially clarified cellular mechanisms. Since cell death is an important mechanism in the appearance and progression of diabetic nephropathy, we studied alteration of several markers of apoptotic pathways signaling in renal tissue of diabetic or prediabetic patients.

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

    Directory of Open Access Journals (Sweden)

    Ramdas Pandhare

    2012-09-01

    Conclusion: These results suggested that APSAE has reduced development of diabetic nephropathy in streptozotocin-induced diabetic rats and could have beneficial effect in reducing the progression of diabetic nephropathy.

  6. Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats

    National Research Council Canada - National Science Library

    Mohan, Aradhana; Singh, Ravi Shankar; Kumari, Manju; Garg, Devika; Upadhyay, Aditya; Ecelbarger, Carolyn M; Tripathy, Sucheta; Tiwari, Swasti

    2016-01-01

    ...). Non-diabetic control (CTRL) rats were injected with vehicle. Insulin (INS) treatment (5U/d, s.c.) was provided to 50% of the DM rats. Urine samples were collected at weeks 3, 6, and 9 following injections and UE prepared...

  7. Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy.

    Science.gov (United States)

    Hsu, Yu-Hsiang; Li, Hsing-Hui; Sung, Junne-Ming; Chen, Wei-Yu; Hou, Ya-Chin; Weng, Yun-Han; Lai, Wei-Ting; Wu, Chih-Hsing; Chang, Ming-Shi

    2017-03-31

    Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.

  8. Diabetic Nephropathy and Microalbuminuria in Pregnant Women With Type 1 and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Damm, Julie Agner; Asbjörnsdóttir, Björg; Callesen, Nicoline Foged

    2013-01-01

    To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol.......To evaluate the prevalence of diabetic nephropathy and microalbuminuria in pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe pregnancy outcomes in these women following the same antihypertensive protocol....

  9. Impaired Podocyte Autophagy Exacerbates Proteinuria in Diabetic Nephropathy.

    Science.gov (United States)

    Tagawa, Atsuko; Yasuda, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-Ichi; Koya, Daisuke; Asanuma, Katsuhiko; Kim, Eun-Hee; Haneda, Masakazu; Kajiwara, Nobuyuki; Hayashi, Kazuyuki; Ohashi, Hiroshi; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2016-03-01

    Overcoming refractory massive proteinuria remains a clinical and research issue in diabetic nephropathy. This study was designed to investigate the pathogenesis of massive proteinuria in diabetic nephropathy, with a special focus on podocyte autophagy, a system of intracellular degradation that maintains cell and organelle homeostasis, using human tissue samples and animal models. Insufficient podocyte autophagy was observed histologically in patients and rats with diabetes and massive proteinuria accompanied by podocyte loss, but not in those with no or minimal proteinuria. Podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in a high-fat diet (HFD)-induced diabetic model for inducing minimal proteinuria. Interestingly, huge damaged lysosomes were found in the podocytes of diabetic rats with massive proteinuria and HFD-fed, podocyte-specific autophagy-deficient mice. Furthermore, stimulation of cultured podocytes with sera from patients and rats with diabetes and massive proteinuria impaired autophagy, resulting in lysosome dysfunction and apoptosis. These results suggest that autophagy plays a pivotal role in maintaining lysosome homeostasis in podocytes under diabetic conditions, and that its impairment is involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy. These results may contribute to the development of a new therapeutic strategy for advanced diabetic nephropathy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Association analysis of canonical Wnt signalling genes in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    David H Kavanagh

    Full Text Available Several studies have provided compelling evidence implicating the Wnt signalling pathway in the pathogenesis of diabetic nephropathy. Gene expression profiles associated with renal fibrosis have been attenuated through Wnt pathway modulation in model systems implicating Wnt pathway members as potential therapeutic targets for the treatment of diabetic nephropathy. We assessed tag and potentially functional single nucleotide polymorphisms (SNPs; n = 31 in four key Wnt pathway genes (CTNNB1, AXIN2, LRP5 and LRP6 for association with diabetic nephropathy using a case-control design.SNPs were genotyped using Sequenom or Taqman technologies in 1351 individuals with type 1 diabetes (651 cases with nephropathy and 700 controls without nephropathy. Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Adjustment for multiple testing was performed by permutation testing.Following logistic regression analysis adjusted by collection centre, duration of T1D, and average HbA1c as covariates, a single SNP in LRP6 (rs1337791 was significantly associated with DN (OR = 0.74; CI: 0.57-0.97; P = 0.028, although this was not maintained following correction for multiple testing. Three additional SNPs (rs2075241 in LRP6; rs3736228 and rs491347 both in LRP5 were marginally associated with diabetic nephropathy, but none of the associations were replicated in an independent dataset. Haplotype and subgroup analysis (according to duration of diabetes, and end-stage renal disease also failed to reveal an association with diabetic nephropathy.Our results suggest that analysed common variants in CTNNB1, AXIN2, LRP5 and LRP6 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes or other members of the Wnt pathway, from involvement in

  11. Maximum home blood pressure is a useful indicator of diabetic nephropathy in patients with type 2 diabetes mellitus: KAMOGAWA-HBP study.

    Science.gov (United States)

    Oyabu, Chikako; Ushigome, Emi; Matsumoto, Shinobu; Tanaka, Toru; Hasegawa, Goji; Nakamura, Naoto; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Tanaka, Muhei; Asano, Mai; Yamazaki, Masahiro; Fukui, Michiaki

    2017-11-01

    Maximum home systolic blood pressure has been shown to predict target organ damage. We aimed to clarify the association between maximum home systolic blood pressure and urine albumin to creatinine ratio, an indicator of early-phase diabetic nephropathy in patients with type 2 diabetes. In 1040 patients, we assessed the relationship of mean or maximum home systolic blood pressure and urine albumin to creatinine ratio, and compared the area under the receiver operating characteristic curve of mean or maximum home systolic blood pressure for diabetic nephropathy (urine albumin to creatinine ratio ⩾30 mg/g Cr). Multivariate linear regression analyses indicated that mean morning systolic blood pressure ( β = 0.010, p diabetic nephropathy in mean and maximum morning systolic blood pressure was 0.667 (0.634-0.700; p diabetic nephropathy in patients with type 2 diabetes.

  12. Optimal dose of losartan for renoprotection in diabetic nephropathy

    DEFF Research Database (Denmark)

    Andersen, Steen; Rossing, Peter; Juhl, Tina R

    2002-01-01

    BACKGROUND: Angiotensin II subtype-1 receptor antagonists represent a valuable new class of drugs in the treatment of diabetic nephropathy. The aim of our study was to evaluate the optimal dose of losartan for renoprotection and blood pressure reduction in diabetic nephropathy. METHODS: Fifty...... consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular...... filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan...

  13. Amelioration of diabetic nephropathy by orange peel extract in rats.

    Science.gov (United States)

    Parkar, Nishad; Addepalli, Veeranjaneyulu

    2014-01-01

    This study was aimed to evaluate the effect of alcoholic orange peel extract (OPE) on streptozotocin-induced diabetic nephropathy. Four weeks after the induction of diabetes, treatment with OPE (100 and 200 mg/kg) was further given for 4 weeks. Treatment with OPE 200 improved renal functions and significantly prevented the increase in creatinine, urea and blood urea nitrogen levels. Histological analysis of the kidneys revealed that tubulointerstitial fibrosis index was significantly decreased in OPE 200-treated group. The results indicated the prevention of diabetic nephropathy in rats by OPE treatment and suggest OPE as a potential treatment option.

  14. Clematis chinensis Extract Protects against Diabetic Nephropathy in ...

    African Journals Online (AJOL)

    mechanism by which CCE protects against DN; possibilities include glucose regulation, lipid metabolism and oxidative stress, and inflammatory cytokine signaling. REFERENCES. 1. Molitch M, DeFronzo R, Franz M. Nephropathy in diabetes. Diabetes Care 2004;27:S79. 2. Cameron NE, Gibson TM, Nangle MR, Cotter MA.

  15. Long-term prevention of diabetic nephropathy: an audit

    DEFF Research Database (Denmark)

    Schjoedt, K.J.; Hansen, H.P.; Tarnow, L.

    2008-01-01

    AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin...

  16. L-Arginine Attenuates Diabetic Nephropathy In Streptozotocin ...

    African Journals Online (AJOL)

    Oxidative stress is widely recognized as a key component in the development and progression of diabetic complications, such as diabetic nephropathy (DN). The present study aimed to evaluate the efficacy of dietary L-arginine supplementation as a potentially novel and useful strategy for the management of oxidative ...

  17. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands : Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    van Dijk, Peter R.; Kramer, Anneke; Logtenberg, Susan J. J.; Hoitsma, Andries J.; Kleefstra, Nanne; Jager, Kitty J.; Bilo, Henk J. G.

    2015-01-01

    Objectives: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. Design: Using the national

  18. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    van Dijk, Peter R.; Kramer, Anneke; Logtenberg, Susan J. J.; Hoitsma, Andries J.; Kleefstra, Nanne; Jager, Kitty J.; Bilo, Henk J. G.

    2015-01-01

    Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. Using the national registry for RRT

  19. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    Dijk, P.R. van; Kramer, A.; Logtenberg, S.J.; Hoitsma, A.J.; Kleefstra, N.; Jager, K.J.; Bilo, H.J.G.

    2015-01-01

    OBJECTIVES: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. DESIGN: Using the national

  20. Mycophenolate Mofetil Ameliorates Diabetic Nephropathy in db/db Mice

    Directory of Open Access Journals (Sweden)

    Jung-Woo Seo

    2015-01-01

    Full Text Available Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Mycophenolate mofetil (MMF has an anti-inflammatory effect, inhibiting lymphocyte proliferation. Previous studies showed attenuation of diabetic nephropathy with MMF, but the underlying mechanisms were unclear. This study aimed to identify the effect of MMF on diabetic nephropathy and investigate its action mechanisms in type 2 diabetic mice model. Eight-week-old db/db and control mice (db/m mice received vehicle or MMF at a dose of 30 mg/kg/day for 12 weeks. MMF-treated diabetic mice showed decreased albuminuria, attenuated mesangial expansion, and profibrotic mRNA expressions despite the high glucose level. The number of infiltrated CD4+ and CD8+ T cells in the kidney was significantly decreased in MMF-treated db/db mice and it resulted in attenuating elevated intrarenal TNF-α and IL-17. The renal chemokines expression and macrophages infiltration were also attenuated by MMF treatment. The decreased expression of glomerular nephrin and WT1 was recovered with MMF treatment. MMF prevented the progression of diabetic nephropathy in db/db mice independent of glycemic control. These results suggest that the effects of MMF in diabetic nephropathy are mediated by CD4+ T cell regulation and related cytokines.

  1. Suramin: a potential therapy for diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Midhun C Korrapati

    Full Text Available OBJECTIVE: To determine whether delayed administration of a single dose of suramin, a drug that has been used extensively in humans to treat trypanosomiasis, attenuates renal injury in a leptin receptor deficient C57BLKS/J db/db type 2 diabetic nephropathy (T2DN mouse model. RESEARCH DESIGN AND METHODS: Groups of female non-diabetic (control db/m and diabetic db/db mice of 8 and 16 weeks of age, respectively, were treated with suramin (10 mg/kg or saline i.v. All animals were euthanized one week later. Measurements in mice 1 week following treatment included the following: body weight; blood glucose; urinary protein excretion; pathological lesions in glomeruli and proximal tubules; changes in protein expression of pro-inflammatory transcription factor nuclear factor κB (NF-κB and intracellular adhesion molecule-1 (ICAM-1, profibrotic transforming growth factor-β1 (TGF-β1, phospho-SMAD-3 and alpha-smooth muscle actin (α-SMA; and immunohistochemical analysis of leukocyte infiltration and collagen 1A2 (COL1A2 deposition. RESULTS: Immunoblot analysis revealed increased NF-κB, ICAM-1, TGF-β1, phospho-SMAD-3, and α-SMA proteins in both 9 and 17 week db/db mice as compared to db/m control mice. Immunohistochemical analysis revealed moderate leukocyte infiltration and collagen 1A2 (COL1A2 deposition in 9 week db/db mice that was increased in the 17 week db/db mice. Importantly, suramin significantly decreased expression of all these markers in 9 week db/db mice and partially decreased in 17 week db/db mice without altering body weight, blood glucose or urinary protein excretion. There was no difference in creatinine clearance between 9 week db/m and db/db mice ± suramin. Importantly, in the 17 week db/db mice suramin intervention reversed the impaired creatinine clearance and overt histological damage. CONCLUSIONS: Delayed administration of a single dose of suramin in a model of T2DN attenuated inflammation and fibrosis as well as improved

  2. Diabetic nephropathy: where are we on the journey from pathophysiology to treatment?

    Science.gov (United States)

    Gallagher, H; Suckling, R J

    2016-07-01

    Diabetic nephropathy affects 30-40% of people with diabetes, and is the leading cause of end-stage kidney disease. The current treatment paradigm relies on early detection, glycaemic control and tight blood pressure management with preferential use of renin-angiotensin system blockade. This strategy has transformed outcomes in diabetic kidney disease over the last 20 years. Over the last two decades we have also witnessed significant advances in the understanding of the pathophysiology of diabetic nephropathy; however, despite this new knowledge, we have yet to develop new treatments of proven efficacy. Whilst a continued emphasis on preclinical and clinical research is clearly needed, clinicians treating people with diabetes should not forget that, in the short term, the greatest gains are likely to be realised by more consistent deployment of existing therapies. © 2016 John Wiley & Sons Ltd.

  3. Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven diabetic nephropathy

    National Research Council Canada - National Science Library

    Shimizu, Miho; Furuichi, Kengo; Toyama, Tadashi; Kitajima, Shinji; Hara, Akinori; Kitagawa, Kiyoki; Iwata, Yasunori; Sakai, Norihiko; Takamura, Toshinari; Yoshimura, Mitsuhiro; Yokoyama, Hitoshi; Kaneko, Shuichi; Wada, Takashi

    2013-01-01

    We evaluated the structural-functional relationships and the prognostic factors for renal events, cardiovascular events, and all-cause mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy...

  4. ADMA reduction does not protect mice with streptozotocin-induced diabetes mellitus from development of diabetic nephropathy.

    Science.gov (United States)

    Rodionov, Roman N; Heinrich, Annett; Brilloff, Silke; Jarzebska, Natalia; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Todorov, Vladimir T; Hugo, Christian P M; Weiss, Norbert; Hohenstein, Bernd

    2017-11-01

    Cardiovascular disease is the major cause of morbidity and mortality in the world. Diabetes and its complications, such as diabetic nephropathy, dramatically increase cardiovascular risk. Association studies suggest that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, plays a role in the pathogenesis of diabetic nephropathy. The major pathway of ADMA catabolism is hydrolysis by dimethylarginine dimethylaminohydrolase 1 (DDAH1). The goal of this study was to test the hypothesis that lowering ADMA by overexpression of DDAH1 protects from development of diabetic nephropathy. Diabetes was induced with streptozotocin (STZ) in wild type and DDAH1 transgenic mice. Healthy mice served as controls. Mice were sacrificed after 20 weeks of diabetes. ADMA levels were assessed by isotope-dilution tandem mass spectrometry, creatinine by standard laboratory methods and albumin by ELISA. Kidney tissues were stained for markers of glomerular cells, cell matrix, inflammation and cell proliferation. STZ led to development of diabetes in all injected mice. Transgenic overexpression of DDAH1 led to a decrease in plasma ADMA levels in healthy animals. Diabetic state itself did not lead to elevation of plasma ADMA levels. Diabetic mice of both genotypes developed albuminuria (27 and 25 vs. 9 and 6 μg albumin/mg creatinine) (p diabetes led to the development of early features of diabetic nephropathy. Overexpression of DDAH1 and lowering of systemic ADMA levels did not prevent these changes, indicating that ADMA is not the major mediator of the early diabetic changes reflected by this experimental model. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chemical substances as risk factors of nephropathy in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2009-12-01

    Full Text Available Although diabetes mellitus, a metabolic disease, does not fall into the group of diseases induced by toxic substances or environmental pollution, there is much evidence that some chemicals have considerable importance in its development. Exposure to substances with potential renal toxicity is especially dangerous for diabetics because it accelerates and intensifies diabetic nephropathy. This paper discusses the relationship between the xenobiotics and the development of diabetes mellitus and diabetic nephropathy with particular emphasis on those substances that causes the greatest damage to the kidneys. These are cadmium, iron, lead, arsenic, polychlorinated organic compounds, nitrogen compounds, and contrast agents. In addition, the mechanisms of diabetes mellitus induction or kidney damage by these xenobiotics are described.

  6. New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human Nephropathy

    Directory of Open Access Journals (Sweden)

    María José Soler

    2012-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease. The use of experimental models of DN has provided valuable information regarding many aspects of DN, including pathophysiology, progression, implicated genes, and new therapeutic strategies. A large number of mouse models of diabetes have been identified and their kidney disease was characterized to various degrees. Most experimental models of type 2 DN are helpful in studying early stages of DN, but these models have not been able to reproduce the characteristic features of more advanced DN in humans such as nodules in the glomerular tuft or glomerulosclerosis. The generation of new experimental models of DN created by crossing, knockdown, or knockin of genes continues to provide improved tools for studying DN. These models provide an opportunity to search for new mechanisms involving the development of DN, but their shortcomings should be recognized as well. Moreover, it is important to recognize that the genetic background has a substantial effect on the susceptibility to diabetes and kidney disease development in the various models of diabetes.

  7. Effect of antihypertensive treatment on progression of incipient diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, Cramer; Mogensen, C E

    1985-01-01

    The aim of the study was to clarify whether antihypertensive treatment with a selective beta blocker would have an effect on the progression rate of kidney disease in patients with incipient diabetic nephropathy. Six male patients with juvenile-onset diabetes with incipient nephropathy (urinary...... albumin excretion above 15 micrograms/min and total protein excretion below 0.5 g/24 hr) were treated with metoprolol (200 mg daily). At the start of the antihypertensive treatment the mean age was 32 years +/- 4.2 (SD). The patients were followed a mean 5.4 years +/- 3.1 (SD) with repeated measurements...

  8. Prevalence of left ventricular hypertrophy in Type I diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Parving, H H

    1999-01-01

    The increased mortality of patients with diabetic nephropathy is mainly due to cardiovascular disease and end stage renal failure. Left ventricular hypertrophy is an independent risk factor for myocardial ischaemia and sudden death. The aim of our cross-sectional study was to evaluate left...... ventricular structure and function in Type I (insulin-dependent) diabetic patients with diabetic nephropathy. M-mode and Doppler echocardiography were done on 105 Type I diabetic patients with diabetic nephropathy [61 men, age (means +/- SD) 44+/-9 years, and albuminuria [median(range)] 567(10-8188) mg/24 h......, serum creatinine 109 (53-558) micromol/l], and 140 Type I diabetic patients with persistent normoalbuminuria [79 men, 47+/-10 years, urinary albumin excretion rate 8 (0-30) mg/24 h, and serum creatinine 81 (55-121) micromol/l]. Patients with and without nephropathy were comparable with respect to sex...

  9. Thyroid Function In Type 2 Diabetes Mellitus and in Diabetic Nephropathy

    Science.gov (United States)

    Rai, Srinidhi; Kumar J, Ashok; K, Prajna; Shetty, Shobith Kumar; Rai, Tirthal; Shrinidhi; Begum, Mohamedi; Shashikala

    2013-01-01

    Introduction: Diabetic patients have higher prevalence of thyroid disorders than the general population which may have an influence on diabetic management. The present study compared the levels of thyroid hormones, serum creatinine, glycated haemoglobin and urine microalbumin between type 2 diabetics without any complications, type 2 diabetics with nephropathy and age and sex matched normal controls. Result: The mean serum T3 level in type 2 diabetics without any complications was 91.27 ± 14.56 ng/dl , in type 2 diabetics with nephropathy was 88.5320 ± 30.87 ng/dl and in controls was 134.98 ± 28.55 ng/dl. The mean serum T4 level in type 2 diabetics without any complications was 7.73 ± 1.42 μg/dl, in type 2 diabetics with nephropathy was 7.25 ± 2.72 μg/dl and in controls was 8.61 ± 1.73 μg/dl. The mean serum TSH level in type 2 diabetics without any complications was 3.99 ± 1.87 μIU/ml, in type 2 diabetics with nephropathy was 4.27 ± 1.62 μIU/ml and in controls was 2.07 ± 1.09 μIU/ml. Correlations between T3, T4, TSH with serum creatinine, glycated haemoglobin were not statistically significant in type 2 diabetes without any complications and diabetic nephropathy. We found a statistically significant correlation between T3 and urine microalbumin in patients with diabetic nephropathy. Conclusion: Failure to recognize the presence of abnormal thyroid hormone levels may be a primary cause of poor management of diabetes mellitus type 2. Therefore there is a need for the routine assay of thyroid hormones in type 2 diabetics and diabetic nephropathy in order to improve the quality of life and reduce the morbidity. PMID:24086845

  10. Role of free radicals in pathogenesis of diabetes nephropathy ...

    African Journals Online (AJOL)

    However, the pathogenesis of diabetes nephropathy remains illusive, notwithstanding, free radicals seem to be the most favorable linkage between all the associated factors suggested. Consequently, free radicals, oxidative stress and antioxidants have become commonly used terms in modern discussions of renal disease ...

  11. Association of Intercellular Adhesion Molecule 1 (ICAM1 with Diabetes and Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Harvest F Gu

    2013-01-01

    Full Text Available Diabetes and diabetic nephropathy are complex diseases affected by genetic and environmental factors. Identification of the susceptibility genes and investigation of their roles may provide useful information for better understanding of the pathogenesis and for developing novel therapeutic approaches. Intercellular adhesion molecule 1 (ICAM1 is a cell surface glycoprotein expressed on endothelial cells and leukocytes in the immune system. The ICAM1 gene is located on chromosome 19p13 within the linkage region of diabetes. In the recent years, accumulating reports have implicated that genetic polymorphisms in the ICAM1 gene are associated with diabetes and diabetic nephropathy. Serum ICAM1 levels in diabetes patients and the icam1 gene expression in kidney tissues of diabetic animals are increased compared to the controls. Therefore, ICAM1 may play a role in the development of diabetes and diabetic nephropathy. In this review, we present genomic structure, variation and regulation of the ICAM1 gene, summarized genetic and biological studies of this gene in diabetes and diabetic nephropathy and discussed about the potential application using ICAM1 as a biomarker and target for prediction and treatment of diabetes and diabetic nephropathy.

  12. Anti-diabetic nephropathy compounds from Cinnamomum cassia.

    Science.gov (United States)

    Yan, Yong-Ming; Fang, Ping; Yang, Mu-Tian; Li, Ning; Lu, Qing; Cheng, Yong-Xian

    2015-05-13

    The bark of Cinnamomum cassia, called 'Rou-Gui', a traditional spice and medicine in China, is used to treat diseases resulted from kidney yang deficiency, including diabetic nephropathy. The aim of this study is to investigate the anti-diabetic nephropathy activity of Rou-Gui and the active compounds in it. The air-dried bark of C. cassia was extracted with 90% EtOH, the obtained residue was successively partitioned by petroleum ether, EtOAc, and n-BuOH followed by concentrating to give petroleum ether (RG-1), EtOAc (RG-2), n-BuOH (RG-3), and water fraction (RG-4), respectively. The anti-diabetic nephropathy activity of fraction (RG-1-4) was evaluated in vitro by inhibiting the expression of fibronectin, monocyte chemoattractant protein-1 and interleukin-6 in high-glucose-induced mesangial cells. By bioassay screenings, repeated column chromatography on fractions of RG-1, 2, and 3, led to the isolation of 23 compounds, whose structures were determined by extensive spectroscopic analyses, and the anti-diabetic nephropathy activity of the isolated compounds was also evaluated. Four new sesquiterpenoids, cinnamoids A-D (1-4), a new natural product (5), and 18 known compounds (6-23) were isolated from the EtOH extract of the bark of C. cassia under the bioassay-guided screenings. The anti-diabetic nephropathy activity assay showed that fractions of RG-1, 2, and 3 could significantly inhibit the production of fibronectin, monocyte chemoattractant protein-1 and interleukin-6 in high-glucose-stimulated mesangial cells at the concentration of 50 μg/ml; and sesquiterpenoids 5, 6, 14 and compound 20 could significantly inhibit the expression of fibronectin, monocyte chemoattractant protein-1 and interleukin-6 at the concentration of 50 μM. The results revealed that sesquiterpenoids may be the active compounds in C. cassia bark on diabetic nephropathy which provided new evidences for the traditional use of this herb to treat diabetic nephropathy and associated kidney

  13. SORBS1 gene, a new candidate for diabetic nephropathy

    DEFF Research Database (Denmark)

    Germain, Marine; Pezzolesi, Marcus G; Sandholm, Niina

    2015-01-01

    cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15 years and no evidence of renal disease. RESULTS: None of the single nucleotide polymorphisms (SNPs) tested in a discovery cohort composed of 683 cases and 779 controls reached genome......-wide statistical significance. The 46 top hits (p Diabetes US (US-GoKinD) study, an independent population of 820 cases and 885 controls. Two SNPs in strong linkage disequilibrium with each other and located in the SORBS1 gene were...... consistently and significantly (p diabetic nephropathy. The minor rs1326934-C allele was less frequent in cases than in controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic nephropathy (OR 0.70; 95% CI 0.60, 0.82). However, this association was not observed...

  14. Concomitant macro and microvascular complications in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Alwakeel Jamal

    2009-01-01

    Full Text Available To determine the prevalence of concomitant microvascular and macrovascular complica-tions of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1% patients (294 (47% were males who developed diabetic nephropathy. Their mean age was 66.9 ± 11.4 years, mean duration of diabetes was 15.4 ± 7.5 years, mean age at the onset of nephropathy was 61.5 ± 12.4 years, and mean duration of nephropathy was 3.9 ± 3.8 years. Concomitant diabetic complications included cataract (38.2%, acute coronary syndrome (36.1%, peripheral neuropathy (24.9%, myocardial infarction (24.1%, background retinopathy (22.4%, stroke (17.6%, proliferative retinopathy (11.7%, foot infection (7.3%, limb amputation (3.7% and blindness (3%. Hypertension was documented in 577 (92.2% patients, dyslipidemia in 266 (42.5% and mortality from all causes in 86 (13.7%. There were 148 (23.6% patients with one complication, 81 (12.9% with two, 83 (13.3% with three, and 61 (9.7% with four or more. Dete-rioration of glomerular filtration rate was observed in 464 (74% patients and doubling of serum creatinine in 250 (39.9%, while 95 (15.2% developed end-stage renal disease (ESRD at the end of study and 79 (12.6% required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05. Relative risks of developing com-plications were significant after the onset of nephropathy; ACS (1.41, MI (1.49, stroke (1.48, diabetic foot (1.6, amputation (1.58 and death (1.93. We conclude that complications of diabetes are aggre-ssive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate progression

  15. Oxidative stress markers in type 2 diabetes patients with diabetic nephropathy.

    Science.gov (United States)

    Chou, Su-Tze; Tseng, Shih-Ting

    2017-04-01

    Epidemiological studies show that 5-40 % of type 2 diabetes (T2DM) patients have diabetic nephropathy, and oxidative stress is one of several underlying mechanisms. We investigated associations between oxidative stress markers and severity of diabetic nephropathy. Fifty-nine T2DM patients from the endocrinology outpatient department were included, and their levels of oxidative stress markers were measured. Three groups were determined by their urine albumin-to-creatinine ratio (UACR): group A (UACR diabetic nephropathy had lower vitamin C levels. Our results identified several oxidative stress markers that may be clinically important in diabetic nephropathy. Studies with larger sample sizes should be undertaken to confirm these findings.

  16. Predicting diabetic nephropathy using a multifactorial genetic model.

    Directory of Open Access Journals (Sweden)

    Ilana Blech

    Full Text Available AIMS: The tendency to develop diabetic nephropathy is, in part, genetically determined, however this genetic risk is largely undefined. In this proof-of-concept study, we tested the hypothesis that combined analysis of multiple genetic variants can improve prediction. METHODS: Based on previous reports, we selected 27 SNPs in 15 genes from metabolic pathways involved in the pathogenesis of diabetic nephropathy and genotyped them in 1274 Ashkenazi or Sephardic Jewish patients with Type 1 or Type 2 diabetes of >10 years duration. A logistic regression model was built using a backward selection algorithm and SNPs nominally associated with nephropathy in our population. The model was validated by using random "training" (75% and "test" (25% subgroups of the original population and by applying the model to an independent dataset of 848 Ashkenazi patients. RESULTS: The logistic model based on 5 SNPs in 5 genes (HSPG2, NOS3, ADIPOR2, AGER, and CCL5 and 5 conventional variables (age, sex, ethnicity, diabetes type and duration, and allowing for all possible two-way interactions, predicted nephropathy in our initial population (C-statistic = 0.672 better than a model based on conventional variables only (C = 0.569. In the independent replication dataset, although the C-statistic of the genetic model decreased (0.576, it remained highly associated with diabetic nephropathy (χ(2 = 17.79, p<0.0001. In the replication dataset, the model based on conventional variables only was not associated with nephropathy (χ(2 = 3.2673, p = 0.07. CONCLUSION: In this proof-of-concept study, we developed and validated a genetic model in the Ashkenazi/Sephardic population predicting nephropathy more effectively than a similarly constructed non-genetic model. Further testing is required to determine if this modeling approach, using an optimally selected panel of genetic markers, can provide clinically useful prediction and if generic models can be

  17. White coat hypertension in NIDDM patients with and without incipient and overt diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Gaede, P; Vedel, P

    1997-01-01

    in normoalbuminuric NIDDM patients resembles that observed in nondiabetic subjects with essential hypertension, whereas the prevalence is significantly lower in NIDDM patients with incipient or overt diabetic nephropathy, suggesting a difference between primary and secondary hypertension.......OBJECTIVE: Early data have suggested a high prevalence of white coat hypertension (approximately 50%) in NIDDM patients. To study this phenomenon further, we determined the prevalence of white coat hypertension in NIDDM patients with normo- or microalbuminuria or with diabetic nephropathy. RESEARCH...... DESIGN AND METHODS: Three groups of hypertensive NIDDM patients (repeated clinic blood pressure > 140/90 mmHg or antihypertensive treatment) attending the Steno Diabetes Center were investigated in a cross-sectional study. Group 1 had normoalbuminuria (a urinary albumin excretion [UAE] rate

  18. Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Smidt, U M; Hommel, E

    1993-01-01

    The effect of long-term, aggressive, antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin-dependent diabetic patients (mean age, 30 years). Renal function was assessed every 4 months by measurement of glomerular filtration rate (GFR) (single...... treatment to 2.5 mL/min/yr (range, 0.5 to 4.8 mL/min/yr) during treatment. The rate of decline in GFR is significantly smaller during the last 6 years compared with the first 3 years in patients who received long-term antihypertensive treatment (> or = 9 years). One patient died from acute myocardial...... infarction (GFR, 46 mL/min/1.73 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy....

  19. Specific Blood Pressure Targets for Patients With Diabetic Nephropathy?

    Science.gov (United States)

    Grassi, Guido; Mancia, Giuseppe; Nilsson, Peter M

    2016-08-01

    Diabetic nephropathy represents a condition frequently detected in current clinical practice characterized by a very high cardiovascular risk profile. Blood pressure reduction via antihypertension drug treatment represents a therapeutic approach capable of exerting favorable effects on renal and cardiovascular outcomes. The purpose of this article is to review the current literature and results of key clinical trials pertaining to blood pressure goals of antihypertension treatment in these patients. The pros and cons of a less or a more intensive blood pressure goal in diabetic nephropathy will be discussed, with particular emphasis on the cardiovascular and renal effects of each therapeutic strategy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Progressive Renal Decline: The New Paradigm of Diabetic Nephropathy in Type 1 Diabetes

    Science.gov (United States)

    2015-01-01

    On the basis of extensive studies in Joslin Clinic patients over 25 years, we propose a new model of diabetic nephropathy in type 1 diabetes. In this model, the predominant clinical feature of both early and late stages of diabetic nephropathy is progressive renal decline, not albuminuria. Progressive renal decline (estimated glomerular filtration rate loss >3.5 mL/min/year) is a unidirectional process that develops while patients have normal renal function. It progresses at an almost steady rate until end-stage renal disease is reached, albeit at widely differing rates among individuals. Progressive renal decline precedes the onset of microalbuminuria, and as it continues, it increases the risk of proteinuria. Therefore, study groups ascertained for microalbuminuria/proteinuria are enriched for patients with renal decline (decliners). We found prevalences of decliners in 10%, 32%, and 50% of patients with normoalbuminuria, microalbuminuria, and proteinuria, respectively. Whether the initial lesion of progressive renal decline is in the glomerulus, tubule, interstitium, or vasculature is unknown. Similarly unclear are the initiating mechanism and the driver of progression. No animal model mimics progressive renal decline, so etiological studies must be conducted in humans with diabetes. Prospective studies searching for biomarkers predictive of the onset and rate of progression of renal decline have already yielded positive findings that will help to develop not only accurate methods for early diagnosis but also new therapeutic approaches. Detecting in advance which patients will have rapid, moderate, or minimal rates of progression to end-stage renal disease will be the foundation for developing personalized methods of prevention and treatment of progressive renal decline in type 1 diabetes. PMID:25998286

  1. [The clinicopathological characteristics of diabetic nephropathy and non-diabetic renal diseases in diabetic patients].

    Science.gov (United States)

    Xu, J; Hu, X F; Huang, W; Shen, P Y; Zhang, W; Ren, H; Li, X; Wang, W M; Chen, N; Pan, X X

    2017-12-01

    Objective: To analyze the clinicopathological characteristics of renal lesions in type 2 diabetic patients and to differentiate diabetic nephropathy (DN) from non-diabetic renal diseases(NDRD). Methods: Type 2 diabetic patients who received renal biopsy in Ruijin Hospital from January 2011 to December 2015 were recruited in this study. Clinical history, laboratory results and pathological data were retrospectively collected. According to the pathological findings, the patients were divided into 3 groups: DN, NDRD, DN+NDRD. Logistic model was applied to explore the independent clinical predictive factors in differentiating DN from NDRD. Results: A total of 207 type 2 diabetic patients received renal biopsy, accounting for 6.82% of all biopsy population. Fifty-one patients were diagnosed with DN, 142 with NDRD and 14 with both DN and NDRD. In NDRD, membranous nephropathy(MN)(34.5%) was the most common finding, followed by IgA nephropathy(19.7%).By contrast, NDRD patients manifested a shorter diabetic course, a higher baseline hemoglobin level, a lower baseline serum creatinine, a higher prevalence of hematuria, a lower prevalence of hypertension and diabetic retinopathy, a better control of blood glucose, better compliance of monitoring blood glucose and less family history of diabetes. In multivariate logistic model, diabetic family history( OR= 4.68, P= 0.04) and long history of diabetes( OR= 1.01, P= 0.02) were risk factors of DN. Conclusion: There is a high prevalence of NDRD in diabetic patients with renal lesions. Family history of diabetes and duration of diabetes are independent predictors of DN.

  2. Genetics of diabetic nephropathy: are there clues to the understanding of common kidney diseases?

    Science.gov (United States)

    Conway, B R; Maxwell, A P

    2009-01-01

    Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches. Copyright 2009 S. Karger AG, Basel.

  3. Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Damm, Peter; Mathiesen, Elisabeth R

    2009-01-01

    To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy.......To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy....

  4. Combined treatment of diabetic nephropathy with alprostadil and calcium dobesilate.

    Science.gov (United States)

    Qin, Lili; Qin, Wenjun; Wang, Jianfei; Lin, Lin

    2017-11-01

    This study investigated the effects of alprostadil combined with calcium dobesilate on the treatment of diabetic nephropathy. We recruited 80 patients with diabetic nephropathy, who were randomly divided into experimental (n=40) and control (n=40) groups. Patients received high-quality low-protein diabetic diet intervention and subcutaneous injection of insulin to adjust blood glucose, combined with antihypertensive, antiplatelet drugs, and other comprehensive treatments. The control group received alprostadil and the experimental group received alprostadil combined with calcium dobesilate. Both groups were treated for 12 weeks as one treatment cycle. The time to remission of clinical symptoms such as mental fatigue and weakness, limb edema, soreness and swelling of waist and knee, cold limbs and limb numbness and pain was significantly shorter in the experimental group than that in the control group (pdobesilate in patients with diabetic nephropathy can effectively relieve clinical symptoms, improve renal functions, reduce blood levels small proteins, alleviate the inflammatory response, and regulate the levels of BDNF and IGF-1, thus improving the clinical treatment effect.

  5. Protease activated receptor 2 in diabetic nephropathy: a double edged sword.

    Science.gov (United States)

    Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, Arnold C

    2017-01-01

    Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and the leading cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is complex, making the development of novel treatments that stop or reverse the progression of microalbuminuria into end stage renal disease a challenge. Protease activated receptor (PAR)-2 has recently been shown to aggravate disease progression in diabetic nephropathy based upon which it was suggested that PAR-2 would be a potential target for the treatment of diabetic nephropathy. To fully appreciate the translational potential of PAR-2 in diabetic nephropathy, we evaluated the effect of PAR-2 deficiency on the development of diabetic nephropathy in a streptozotocin-induced diabetes model characteristic of type 1 diabetes. Although diabetic PAR-2 deficient mice showed reduced albuminuria compared to diabetic wild type mice, an increase in mesangial expansion was evident in the PAR-2 deficient mice. No differences were observed in blood glucose levels, podocyte numbers or in glomerular vascular density. These results show that PAR-2 plays a dual role in the development of streptozotocin-induced diabetic nephropathy and may thus not be the eagerly awaited novel target to combat diabetic nephropathy. Targeting PAR-2 should consequently only be pursued with great care in a clinical setting.

  6. Increased left ventricular mass in normotensive type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Sato, A; Tarnow, L; Parving, H H

    1998-01-01

    OBJECTIVE: Diabetic nephropathy increases the risk of premature cardiovascular disease and sudden death, particularly in type 1 diabetic patients. One possible mechanism for this risk may be left ventricular hypertrophy. In our study, we aimed to evaluate left ventricular structure and function...... in normotensive type 1 diabetic patients with and without nephropathy. RESEARCH DESIGN AND METHODS: M-mode and Doppler echocardiography was performed in 17 type 1 diabetic patients with nephropathy (albuminuria [median (range)], 345 (135-2,846) mg/24 h) and compared with 34 normotensive, normoalbuminuric (10 [3......-30] mg/24 h) type 1 diabetic patients matched for arterial blood pressure (mean +/- SD) ([134/77] +/- [13/7] vs. [129/78] +/- [12/7] mmHg), age (40 +/- 11 vs. 42 +/- 10 years), duration of diabetes (28 +/- 7 vs. 28 +/- 6 years), and BMI (24.2 +/- 4.2 vs. 24.6 +/- 2.4 kg/m2). RESULTS: Left ventricular...

  7. Plasma proteome analysis of patients with type 1 diabetes with diabetic nephropathy

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Hansen, Henning Gram; Lajer, Maria

    2010-01-01

    As part of a clinical proteomics program focused on diabetes and its complications we are looking for new and better protein biomarkers for diabetic nephropathy. The search for new and better biomarkers for diabetic nephropathy has, with a few exceptions, previously focused on either hypothesis......-driven studies or urinary based investigations. To date only two studies have investigated the proteome of blood in search for new biomarkers, and these studies were conducted in sera from patients with type 2 diabetes. This is the first reported in depth proteomic study where plasma from type 1 diabetic...... patients was investigated with the goal of finding improved candidate biomarkers to predict diabetic nephropathy. In order to reach lower concentration proteins in plasma a pre-fractionation step, either hexapeptide bead-based libraries or anion exchange chromatography, was performed prior to surface...

  8. Recent advances in managing and understanding diabetic nephropathy [version 1; referees: 3 approved

    OpenAIRE

    Tang, Sydney C.W.; Gary C. W. Chan; Kar Neng Lai

    2016-01-01

    Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approache...

  9. Recent advances in managing and understanding diabetic nephropathy [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Sydney C.W. Tang

    2016-05-01

    Full Text Available Diabetic nephropathy is the commonest cause of end-stage renal disease in most developed economies. Current standard of care for diabetic nephropathy embraces stringent blood pressure control via blockade of the renin-angiotensin-aldosterone system and glycemia control. Recent understanding of the pathophysiology of diabetic nephropathy has led to the development of novel therapeutic options. This review article focuses on available data from landmark studies on the main therapeutic approaches and highlights some novel management strategies.

  10. Urinary microRNA profiling in the nephropathy of type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Christos Argyropoulos

    Full Text Available Patients with Type 1 Diabetes (T1D are particularly vulnerable to development of Diabetic nephropathy (DN leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease.We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N matched against 10 patients who went on to develop overt nephropathy (DN, 10 patients with intermittent microalbuminuria (IMA matched against 10 patients with persistent (PMA microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease.Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes.

  11. Protease activated receptor 2 in diabetic nephropathy: a double edged sword

    NARCIS (Netherlands)

    Waasdorp, Maaike; Duitman, Janwillem; Florquin, Sandrine; Spek, Arnold C.

    2017-01-01

    Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and the leading cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is complex, making the development of novel treatments that stop or reverse the progression of microalbuminuria into

  12. Time course of the antiproteinuric and antihypertensive effect of losartan in diabetic nephropathy

    DEFF Research Database (Denmark)

    Andersen, Steen; Jacobsen, Peter; Tarnow, Lise

    2003-01-01

    is unknown. We evaluated the time course of the antihypertensive and antialbuminuric effect after initiation of AT1 receptor blockade by losartan in diabetic nephropathy. METHODS: Ten hypertensive type 1 diabetic patients with diabetic nephropathy were included in the study. After a washout period of 4 weeks...

  13. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease

    Directory of Open Access Journals (Sweden)

    Nazar Chaudhary Muhammad Junaid

    2014-01-01

    Full Text Available Diabetes mellitus is a leading epidemic of the present world. It is considered the leading cause of death among end-stage renal disease (ESRD patients. The complications associated with diabetes mellitus have boosted the number of deaths in the last years. These complications are the result of long lasting effects of diabetes mellitus on the glomerular microvasculature of the kidney. Diabetic nephropathy (DN develops in patients with several years’ medical history of diabetes and renal failure. However, research shows that patients with type 1 diabetes progress early to ESRD as compared to those with type 2. DN is more prevalent in ethnic minorities as compared to other groups in society. There are new and different treatment options available since medical science has progressed due to increased research efforts. Unfortunately, there is no permanent cure. The aim of this article is to explore the research of therapeutic strategies currently in use by medical practitioners in order to increase understanding of DN.

  14. Effect of Ayurvedic management in 130 patients of diabetic nephropathy

    Science.gov (United States)

    Patel, Kalapi; Gupta, S. N.; Shah, Namrata

    2011-01-01

    Diabetic nephropathy is a specific form of renal disease. It is a major cause of renal insufficiency and ultimately of death. The present study has been carried out to prove the efficacy of Ayurvedic drugs in the management of diabetic nephropathy, which can be helpful in reducing the need of dialysis and avoiding or delaying renal transplantation. A total of 130 patients of this disease were treated in IPD (Group A) and OPD (Group B). Ayurvedic formulations including Gokshuradi Guggulu, Bhumyamalaki, Vasa and Shilajatvadi Vati were given to all the patients for 2 months. Group A patients were given special planned food. Results were analyzed statistically using “t” test. In group A patients, highly significant reduction was found in the values of serum creatinine, blood urea and urinary excretion of albumin. Marked improvement was found in the patients’ general physical well-being, together with reduction in symptoms, in group A patients. This shows the importance of Pathyapathya in Ayurvedic management of the disease. This management may bring some new hope to the patients of diabetic nephropathy, which usually terminates to chronic renal failure and ultimately to death. Further studies are being carried out in this regard. PMID:22131758

  15. Subclinical hypothyroidism and diabetic nephropathy in Iranian patients with type 2 diabetes.

    Science.gov (United States)

    Mansournia, N; Riyahi, S; Tofangchiha, S; Mansournia, M A; Riahi, M; Heidari, Z; Hazrati, E

    2017-03-01

    Association of subclinical hypothyroidism with type 2 diabetes and its complications has been previously documented. These reports were, however, inconclusive and mainly gathered from Chinese and East Asian populations. In this study, we aimed to determine the prevalence of subclinical hypothyroidism and its relationship with diabetic nephropathy in Iranian individuals with type 2 diabetes, drawn from a white Middle Eastern population with an increasing prevalence of diabetes. In this cross-sectional study, 255 Iranian participants with type 2 diabetes and without history of thyroid disorders were included. Patients with TSH > 4.2 mIU/L and normal T4 were classified as having subclinical hypothyroidism. Diabetic nephropathy was diagnosed based on abnormal 24-h urinary albumin or protein measurements (24-h urinary albumin ≥30 mg/day or 24-h urinary protein ≥150 mg/day). Multivariate logistic regression was employed to obtain the OR for the relationship between subclinical hypothyroidism and diabetic nephropathy. We found that subclinical hypothyroidism and diabetic nephropathy were as prevalent as 18.1 and 41.2 %, respectively, among the participants. We also found that subclinical hypothyroidism was independently associated with higher rates of diabetic nephropathy, after multivariable adjustment (OR [95 % CI] 3.23 [1.42-7.37], p = 0.005). We found that the prevalence of subclinical hypothyroidism in Iranian diabetic population was among the highest rates reported to date. Our data supported the independent association of subclinical hypothyroidism with diabetic nephropathy, calling for further investigations to evaluate their longitudinal associations.

  16. Diabetic nephropathy in a nonobese mouse model of type 2 diabetes mellitus.

    Science.gov (United States)

    Mallipattu, Sandeep K; Gallagher, Emily J; LeRoith, Derek; Liu, Ruijie; Mehrotra, Anita; Horne, Sylvia J; Chuang, Peter Y; Yang, Vincent W; He, John C

    2014-05-01

    A large body of research has contributed to our understanding of the pathophysiology of diabetic nephropathy. Yet, many questions remain regarding the progression of a disease that accounts for nearly half the patients entering dialysis yearly. Several murine models of diabetic nephropathy secondary to Type 2 diabetes mellitus (T2DM) do exist, and some are more representative than others, but all have limitations. In this study, we aimed to identify a new mouse model of diabetic nephropathy secondary to T2DM in a previously described T2DM model, the MKR (MCK-KR-hIGF-IR) mouse. In this mouse model, T2DM develops as a result of functional inactivation of insulin-like growth factor-1 receptor (IGF-1R) in the skeletal muscle. These mice are lean, with marked insulin resistance, hyperinsulinemia, hyperglycemia, and dyslipidemia and thus are representative of nonobese human T2DM. We show that the MKR mice, when under stress (high-fat diet or unilateral nephrectomy), develop progressive diabetic nephropathy with marked albuminuria and meet the histopathological criteria as defined by the Animal Models of Diabetic Complications Consortium. Finally, these MKR mice are fertile and are on a common background strain, making it a novel model to study the progression of diabetic nephropathy.

  17. Unchanged incidence of diabetic nephropathy in IDDM patients

    DEFF Research Database (Denmark)

    Rossing, P; Rossing, K; Jacobsen, P

    1995-01-01

    in the incidence of diabetic nephropathy. All 356 patients in whom IDDM was diagnosed before the age of 41 years between 1965 and 1979, identified in 1984, were followed until 1991 or until death. All patients were Caucasians and resided in Copenhagen. The cumulative incidences (life-table method) of diabetic......% (onset of diabetes 1975-1979, n = 113), respectively (NS at 15 years). The prevalence of persistent microalbuminuria (31-299 mg/24 h) at time of follow-up was 24% (95% confidence interval: 16-33) in the group with onset of diabetes in 1965-1969, 28% (20-36) with onset of diabetes in 1970-1974, and 19...

  18. Remission and regression in the nephropathy of type 1 diabetes when blood pressure is controlled aggressively

    DEFF Research Database (Denmark)

    Hovind, P; Rossing, P; Tarnow, L

    2001-01-01

    years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. Blood...... and regression in a sizable fraction of patients with diabetic nephropathy. Lower arterial blood pressure, reduced albuminuria, and better glycemic control were predictors of regression of diabetic nephropathy.......BACKGROUND: Diabetic nephropathy is a chronic, progressive kidney disease with a mean rate of decline of in glomerular filtration rate (GFR) of 10 to 12 mL/min/year (natural history). The introduction of aggressive antihypertensive treatment has improved the renal prognosis during the last decades...

  19. Diabetic nephropathy: glomerular filtration rate and estimated creatinine clearance

    OpenAIRE

    Guimarães, J; Bastos, M.; Melo, M.; Carvalheiro, M.

    2007-01-01

    OBJECTIVE: To assess in diabetic nephropathy, the accuracy of estimated creatinine clearance (calculated with the Cockroft Gault formula) and the clearance of the Tc99m-DTPA, to measure the glomerular filtration rate (GFR). PATIENTS AND METHODS: We analysed the GFR measure by Tc99m-DTPA method and the estimated by the Cockroft Gault formula, in 21 subjects with type 1 or type 2 diabetes. RESULTS: There was a strong positive correlation between the two methods but the Cockroft Gault formula un...

  20. Angiotensin-converting enzyme inhibition in diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P; Hommel, E

    1995-01-01

    The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive......, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P ....01), hemoglobin A1c (r = 0.69, P concentration (r = 0.51, P

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVE: Diabetic nephropathy is associated with aberrant glomerular filtration of serine proteases. The study was designed to test the hypothesis that the epithelial sodium channel is activated proteolytically by urine plasmin in diabetic nephropathy and mediates renal sodium retention. METHOD...

  2. Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Hommel, E

    1992-01-01

    Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute...... to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50...... healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1...

  3. Serum uric acid as a new player in the development of diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, Peter; Rossing, Peter; Johnson, Richard J

    2011-01-01

    The pathogenesis of diabetic nephropathy is complex and still not fully elucidated. Uric acid has been associated with renal disease, even though hyperuricemia may be a marker of or by itself be responsible for microvascular disease in diabetes. In animal models, elevated level of uric acid can...... lead to arteriolopathy of preglomerular vessels, impaired autoregulation, glomerular hypertension, as well as endothelial dysfunction. Kidney damage in hyperuricemic rats is not dependent on blood pressure, and instead involves the renin-angiotensin system. In patients with diabetes, serum uric acid...... early in the course of diabetes is significantly, and independent of confounders, associated with later development of persistent macroalbuminuria. Therefore, uric acid may be a novel and important player in the pathogenesis of microvascular complications in diabetes. A dose-response relationship...

  4. Urinary sulphate excretion and progression of diabetic nephropathy in Type1 diabetes

    NARCIS (Netherlands)

    Andresdottir, G.; Bakker, S. J. L.; Hansen, H. P.; Parving, H-H; Rossing, P.

    Aims Hydrogen sulphide levels are reduced in many disease states, including diabetes and end-stage renal disease. We aimed to determine whether urinary sulphate excretion, as a proxy for hydrogen sulphide, was associated with progression of diabetic nephropathy. Methods We conducted a post-hoc study

  5. Increased sympathetic activity during sleep and nocturnal hypertension in Type 2 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Hansen, H P; Jacobsen, P

    1999-01-01

    (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly...

  6. Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

    DEFF Research Database (Denmark)

    Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A

    2011-01-01

    Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loc...

  7. Diabetic nephropathy in a tertiary care clinic in South Africa: a cross ...

    African Journals Online (AJOL)

    2014-11-20

    Nov 20, 2014 ... Certain ethnic groups, such as Native Americans, and. Mexican and African Americans, demonstrate a higher prevalence rate of severe nephropathy in comparison to. Caucasians.5,6. The prevalence of diabetic nephropathy ranges from. 32-57% in Africa, and overt proteinuria is found in 5-28% of diabetic ...

  8. Rise in albuminuria and blood pressure in patients who progressed to diabetic nephropathy in the Diabetes Control and Complications Trial.

    Science.gov (United States)

    Thomas, W; Shen, Y; Molitch, M E; Steffes, M W

    2001-02-01

    The Diabetes Control and Complications Trial (DCCT) enrolled 1441 participants to address the role of intensive therapy for type 1 diabetes mellitus on the onset and progression of microvascular complications. To examine the timing of elevated systolic BP (SBP) and diastolic BP (DBP) and increased albumin excretion rate (AER) in the progression to clinical diabetic nephropathy (AER > 300 mg/24 h on two consecutive visits from a baseline of AER AER and hemoglobin A(1c), but who did not progress to clinical diabetic nephropathy-matched controls. In the conventional treatment group, the 21 progressors exhibited a significant rise in mean AER (above their own baseline levels and above values in the matched controls) at year 2 of the DCCT. In contrast, the progressors' mean DBP and SBP were not significantly higher than baseline until year 3 (DBP) or year 4 (SBP) and not significantly higher than the matched controls until year 4 (both DBP and SBP). On the individual level, 19 of 21 (90%) progressors reached clinical diabetic nephropathy before the diagnosis of hypertension (140/90 mmHg). In the intensive treatment group, however, the rise in DBP preceded the rise in AER by 1 to 2 yr among the six progressors. Both intensively treated progressors who experienced hypertension reached this before AER > 300 mg/24 h. These results underline the early and prognostic rise in AER in diabetic patients, but only in those who received conventional treatment. The evolution of diabetic renal disease may follow a different course in patients who receive intensive diabetic treatment.

  9. Non-Alcoholic Fatty Liver Disease Is not Related to the Incidence of Diabetic Nephropathy in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Chun-Shan Bi

    2012-11-01

    Full Text Available To analyze the association between non-alcoholic fatty liver disease (NAFLD and the incidence of diabetic nephropathy in patients with type 2 diabetes, the incidence of diabetic nephropathy was assessed in 413 type 2 diabetic patients, by testing the 24 h urinary albumin excretion rate (UAER. The NAFLD was diagnosed based on patient’s medical history and liver ultrasound. The difference in diabetic nephropathy incidence between patients with and without NAFLD was tested by χ2. Multivariate logistic regression analysis was used to assess the factors associated with diabetic nephropathy among type 2 diabetic patients. Total 363 out of 413 type 2 diabetic patients were enrolled in this study. The incidences of NAFLD and diabetic nephropathy in participants were approximately 56% (202/363 and 38% (137/363 respectively, and there was no significant difference in the prevalence of diabetic nephropathy between patients with and without NAFLD (37.1% vs. 38.5%, p = 0.787. The duration of diabetes (odds ratio [OR] 1.065, 95% confidence interval [CI] 1.014–1.120, p = 0.012, waist circumference (OR 1.077, 95% CI 1.040–1.116, p = 0.000, and fasting blood glucose (FBG; OR 1.136, 95% CI 1.023–1.1262, p = 0.017 were significantly associated with diabetic nephropathy, whereas sex, high blood pressure, total cholesterol (TC, triglyceride (TG, and ankle brachial pressure index (ABI were not significantly associated with the disorder. The present results suggest that NAFLD is not related to the incidence of diabetic nephropathy in type 2 diabetes, but the duration of diabetes, waist circumference, and FBG are important factors for diabetic nephropathy in type 2 diabetes.

  10. Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Ahuja, Monica; Rai, Taranjit Singh

    2008-01-01

    Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy. Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. We evaluated the association...... of the constitutive endothelial nitric oxide synthase gene (eNOS) polymorphisms with type 2 diabetic nephropathy. We genotyped three polymorphisms of eNOS (Two SNPs: -786T > C, 894G > T and one 27-bp repeat polymorphism in Intron 4 (27VNTR)) in type 2 diabetic nephropathy patients (cases: n = 195) and type 2 diabetic...

  11. Study of neutrophil-lymphocyte ratio as novel marker for diabetic nephropathy in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sagar Ashokrao Khandare

    2017-01-01

    Full Text Available Introduction: Diabetic nephropathy (DN is a microvascular complication of diabetes. DN is clinically manifested as an increase in urine albumin excretion. Total white blood cell count is a crude but sensitive indicator of inflammation and studied in many cardiac and noncardiac diseases as an inflammatory marker such as acute myocardial infarction, stroke, and heart failure. In this study, the association of neutrophil-lymphocyte ratio (NLR with DN is studied. Patients and Methods: It is an observational cross-sectional study. Totally 115 diagnosed type 2 diabetes mellitus patients were registered in this study. NLR was calculated by analyzing differential leukocyte count in complete blood picture. Albuminuria was tested by MICRAL-II TEST strips by dipstick method. Results: Totally 115 diabetic patients were registered. About 56 patients had DN and 59 had normal urine albumin. Mean NLR for a normal group is 1.94 ± 0.65 and in DN group is 2.83 ± 0.85 which was highly significant (P < 0.001. Estimated glomerular filtration rate (P = 0.047 and serum glutamate pyruvate transaminase (P < 0.001 were also significant. Conclusion: The results of our study show that there was a significant relation between NLR and DN. Therefore, NLR may be considered as a novel surrogate marker of DN in early stages.

  12. Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract

    Directory of Open Access Journals (Sweden)

    Snehal Nitin Mestry

    2017-07-01

    Full Text Available With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum, due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p. in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg for 8 weeks. At the end of the experimental period, body and kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.

  13. Alterations of urinary metabolite profile in model diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  14. Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians

    DEFF Research Database (Denmark)

    Cheema, Balneek Singh; Iyengar, Sreenivasa; Ahluwalia, Tarun Veer Singh

    2012-01-01

    Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association...... with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients....

  15. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    Science.gov (United States)

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  16. Inhibition of RAS in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Yacoub R

    2015-04-01

    Full Text Available Rabi Yacoub, Kirk N Campbell Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Diabetic kidney disease (DKD is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII, the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population. Keywords: renin–angiotensin system, diabetic kidney disease, angiotensin II, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers

  17. Small dense low-density lipoprotein as a potential risk factor of nephropathy in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Essam Abd-Allha

    2014-01-01

    biomarker to be used in conjunction with other biochemical markers for early diagnosis, assessment, and follow-up of diabetic nephropathy.

  18. The role of the complement system in diabetic nephropathy

    DEFF Research Database (Denmark)

    Flyvbjerg, Allan

    2017-01-01

    -threatening disease. An increasing body of evidence points toward a role of the complement system in the pathogenesis of diabetic nephropathy. For example, circulating levels of mannose-binding lectin (MBL), a pattern recognition molecule of the innate immune system, have emerged as a robust biomarker...... for the development and progression of this disease, and evidence suggests that MBL, H-ficolin, complement component C3 and the membrane attack complex might contribute to renal injury in the hyperglycaemic mileu. New approaches to modulate the complement system might lead to the development of new agents to prevent...

  19. Beneficial effect of camel milk in diabetic nephropathy.

    Science.gov (United States)

    Agrawal, Rajendra Prasad; Dogra, Rutba; Mohta, Niranjana; Tiwari, Raksha; Singhal, Sushma; Sultania, Surender

    2009-08-01

    Diabetic nephropathy is originally microvascular in nature and is widely considered an important complication of diabetes. The present study was carried out to determine the efficacy of camel milk in controlling diabetic nephropathy. Twenty-four type-1 diabetic patients were randomly recruited from the outpatient diabetic clinic in PBM Hospital, Bikaner, India. All subjects gave their written consent before participation in the study. Patients with any acute metabolic complications were not included in the study. Eligible patients entered a run-in period of 1 month in which they were oriented to achieve the best possible glycemic control through standardized diet, standardized exercise regimen and insulin administration. During this period frequent monitoring of blood sugar was performed to maintain euglycemia. At the end of the run-in period, a base line evaluation was performed, then these patients were given camel milk in addition with usual care for six months. Urine microalbumin and blood sugar was measured twice a week before breakfast and dinner. There was a significant improvement in the microalbuminuria (119.48 +/- 1.68 to 22.52 +/- 2.68; p camel milk for 6 months. A significant reduction in the mean dose of insulin for obtaining glycemic control was achieved (41.61 +/- 3.08 to 28.32 +/- 2.66; p camel milk in controlling microalbuminuria levels in type-1 diabetic patients. It was observed that after adding camel milk to the usual regimen an improvement in microalbuminuria was reached (119.48 +/- 1.68 to 22.52 +/- 2.68; p camel milk. The mechanism behind this effect is still unknown.

  20. Alterations of urinary metabolite profile in model diabetic nephropathy.

    Science.gov (United States)

    Stec, Donald F; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

    2015-01-09

    Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS(-/-) C57BLKS and eNOS(-/-) C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS(-/-) C57BLKS and eNOS(-/-) C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in metabolomic studies relevant to human pathology. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Study of Prevalence and Stages of diabetic nephropathy in a rural tertiary care centre - Southern India (2011-12

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    Anil NS

    2012-11-01

    Full Text Available Type 2 diabetes mellitus (T2DM is an alarming health care concern the world over affecting more-than 220 million people worldwide according to World Health Organization. Kidney disease in diabetic patients is clinically characterized by increasing rates of urinary albumin excretion (UAE, starting from normoalbuminuria, which progresses to microalbuminuria, macroalbuminuria and eventually to End-Stage Renal Disease. Diabetic nephropathy has been categorized into stages based on the values of urinary albumin excretion and estimated glomerular filtration (eGFR. There is accumulating evidence suggesting that the risk for developing diabetes nephropathy and cardiovascular disease starts when UAE values are still within normoalbuminic range. Objective: To study the prevalence and stages of nephropathy in T2DM patients and to compare albumin levels with glycemic control in rural population. Methodology: Cross-sectional study was carried out from January 2011 to April 2012 among diabetic patients attending General Medicine department in RL Jalappa Hospital. Random blood sample and spot urine sample was collected for analysis and the data was collected in a predesigned, pretested semi-structured questionnaire. Results: The prevalence of diabetic nephropathy in our study was 37.02%. The prevalence microalbuminuria was 30.79% in males and 24.46% in females. The prevalence of overt nephropathy was 9.27% in males and 6.73% in females. Around 62.97% were in microalbuminuric range. 75.76% of the patients had poor glycemic control, but among patients with poor glycemic control 79.78% had overt nephropathy and 86.80% had microalbuminuria. Among patients with good glycemic control 20.28% had overt nephropathy and 13.19% had microalbuminuria. Conclusion: Microalbuminuria was earliest sign in Diabetic Nephropathy (DN. Progression of DN can be prevented on early detection. Poor glycemic control and duration of diabetes was associated with increase in UAE level and

  2. Smoking as a risk factor for diabetic nephropathy: a meta-analysis.

    Science.gov (United States)

    Su, Sensen; Wang, Wanning; Sun, Tao; Ma, Fuzhe; Wang, Yue; Li, Jia; Xu, Zhonggao

    2017-10-01

    Previous studies have investigated the connection between diabetic nephropathy and smoking, and reported widely varying rates. This study aimed to systematically analyze the impact of smoking on diabetic nephropathy. We searched the PubMed and EMBASE electronic databases to identify relevant English-language studies published up to March 2016. Eligible studies were selected using inclusion and exclusion criteria. Data for each study were extracted independently by two authors. The homogeneity of the effect size across the studies was tested. Odds ratio (OR) was calculated by using the random-effect model. Sensitivity analysis was performed to reduce heterogeneity, and publication biases were examined. A total of 21 eligible studies were selected and pooled analyzed. No significant differences in demographic characteristics were found between patients with diabetic nephropathy and those with non-diabetic nephropathy. Significant heterogeneity across studies was found except those of diabetes mellitus controls. The aggregate OR of smoking in the patients with diabetic nephropathy in comparison with those with non-diabetic nephropathy was 1.70 (95% confidence interval 1.48-1.95). No evidence of publication bias was found. Our findings indicate that smoking is a significant risk factor for diabetic nephropathy in diabetic patients.

  3. Left ventricular hypertrophy in non-insulin-dependent diabetic patients with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, F S; Ali, S; Rossing, P

    1997-01-01

    The aim of our cross-sectional case-control study was to evaluate putative mechanisms of the increased cardiac morbidity and mortality in NIDDM patients with or without diabetic nephropathy. Fifty-one NIDDM patients with diabetic nephropathy (38 males, age 61 +/- 8 years, group 1), 53 NIDDM...... determined by echocardiography. LVMI was elevated, mean +/- SE, in group 1: 157 +/- 6 g m(-2), and in group 2: 139 +/- 7 g m(-2), as compared with group 3: 95 +/- 5 g m(-2) (p hypertrophy (LVH) (LVMI...... systolic function which may constitute independent risk factors for fatal and non-fatal cardiac events....

  4. A System-Wide Approach to Diabetic Nephropathy

    KAUST Repository

    Palafox, Luis

    2011-07-07

    Diabetes mellitus is a complex human disease that affects more than 280 million people worldwide. One of the diabetic long-term complications is diabetic nephropathy that it is responsible for 50% of all end-stage renal disease. The complexity of diabetes and the lack of comprehensive systematic studies have halted the development of drugs and clinical therapies for the treatment of diabetes and its major complications. The present project, based on the db/db mice as animal model, investigates the repercussions of diabetes mellitus in the transcriptome as well as the mechanism of action of pirfenidone, an antifibrotic drug, in the treatment of diabetic nephropathy. The study was centered on the system-wide measurements transcriptional state of the mouse kidney. The expression profile of three experimental groups: control, diabetic, and diabetic treated with the drug, were analyzed using expression clustering, gene ontology enrichment analysis, protein-protein interaction network mapping, and gene expression behavior. The results show significant expression dysregulation of genes involved in RNA processing, fatty acid oxidation, and oxidative phosphorylation under the diabetic condition. The drug is able to regulate the expression levels of RNA processing genes but it does not show any effect in the expression profile of genes required in the oxidative phosphorylation and in the fatty acid metabolism. In conclusion diabetes mellitus induce the dysregulation of the splicing apparatus, the oxidative phosphorylation, and the fatty acid metabolic pathway at an expression level. The malfunction of these biological pathways causes cellular stress by increasing the concentration of reactive oxygen species within the cell due to a high oxidative and respiratory activity of mitochondria in addition to the increased demand of the folding machinery as a consequence of a dysregulation of the splicing apparatus. Pirfenidone regulates the expression of RNA processing genes mainly

  5. Albumin antioxidant response to stress in diabetic nephropathy progression.

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    Rafael Medina-Navarro

    Full Text Available BACKGROUND: A new component of the protein antioxidant capacity, designated Response Surplus (RS, was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. METHODS/PRINCIPAL FINDINGS: Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR. In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = -0.83, p<0.0001. Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = -0.47, p < 0.001; R = -0.68, p<0.0001; R = 0.44, p < 0.001; and R = 0.72, p < 0.0001. CONCLUSION/SIGNIFICANCE: The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy.

  6. Pathophysiology of diabetic nephropathy: a literature review

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    Carlos Eduardo Meza Letelier

    2017-01-01

    Full Text Available Resumen La enfermedad renal crónica es una complicación frecuente en la diabetes mellitus. Su importancia radica en la alta prevalencia y la proyección a futuro que ésta tiene. Se asocia a altos gastos en salud y además a deterioro cardiovascular global. La fisiopatología del desarrollo de esta enfermedad está siendo estudiada y se sabe que en ella participan una serie de vías moleculares complejas que determinan una enfermedad microvascular. En esta revisión se intenta abordar las vías conocidas en el desarrollo de nefropatía diabética, con el fin de comprender mejor posibles blancos terapéuticos que se podrían desarrollar.

  7. Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Jensen, J S

    1991-01-01

    -matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure...... was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes......Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we...

  8. Long-term expression of glomerular genes in diabetic nephropathy.

    Science.gov (United States)

    Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

    2018-01-11

    Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney

  9. Endocannabinoids and the renal proximal tubule: an emerging role in diabetic nephropathy.

    Science.gov (United States)

    Jenkin, Kayte A; Verty, Aaron N A; McAinch, Andrew J; Hryciw, Deanne H

    2012-11-01

    Diabetic nephropathy is a leading cause for the development of end-stage renal disease. In diabetes mellitus, a number of structural changes occur within the kidney which leads to a decline in renal function. Damage to the renal proximal tubule cells (PTCs) in diabetic nephropathy includes thickening of the basement membrane, tubular fibrosis, tubular lesions and hypertrophy. A clearer understanding of the molecular mechanisms involved in the development of diabetic kidney disease is essential for the understanding of the role cellular pathways play in its pathophysiology. The endocannabinoid system is an endogenous lipid signalling system which is involved in lipogenesis, adipogenesis, inflammation and glucose metabolism. Recent studies have demonstrated that in diabetic nephropathy, there is altered expression of the endocannabinoid system. Future investigations should clarify the role of the endocannabinoid system in the development of diabetic nephropathy and within this system, identify potential therapeutics to reduce the burden of this disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. [Puberty, pregnancy, gender and hormonal status--putative risk factors for diabetic nephropathy].

    Science.gov (United States)

    Panduru, N M; Chivu, Laura Ioana; Chivu, R D; Bădărău, Ioana Anca; Albu, D F; Fica, Simona; Ion, Daniela Adriana

    2009-01-01

    Contemplation of non-genetic risk factors that are influencing the onset and development of diabetic nephropathy (diabetic kidney disease--DKD) is very important. This article is integrative, assessing the existent data about several possible risk factors for DKD. Because the age of onset and postpubertal duration of diabetes seems to be strongly correlated with DKD, it is feasible for puberty to be another independent risk factor. Data analysis regarding puberty and possible explanatory mechanisms to link it with DKD, as the connection with DKD of other situations, with special hormonal status (like pregnancy), is also part of this article. Summing up the data about hormonal status, we can conclude that ANF levels are a risk factor for diabetic nephropathy because they are implicated in diminution of urinary Na elimination and hypertension and subsequent urinary albumin excretion (UAE) in case of inadequate glycaemic control. The evidences regarding GH are indicating that it is a risk factor for DKD and that he is probably implicated in glomerular hypertrophy onset at puberty. The urinary elimination levels of GH are very strong correlated with UAE being putative early marker for DKD. Also the GH deficiency seems to be a protective mechanism for DKD apparition. GH is strongly correlated with IGF-1 that has very high urinary levels in microalbuminuric patients. These levels are very well related to UAE, kidney volume--important markers for glomerular hypertrophy. The evidences accumulated until now regarding the role of masculine gender, testosterone and estrogens in DKD are inarticulate.

  11. Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

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    Shinji Kume

    2014-01-01

    Full Text Available Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.

  12. Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Christensen, P K; Rossing, P; Nielsen, F S

    1999-01-01

    AIMS: To determine the natural course of kidney function and to evaluate the impact of putative progression promoters in Caucasian Type 2 diabetes mellitus (DM) patients with diabetic nephropathy who had never received any antihypertensive treatment. METHODS: A long-term observational study of 13...... normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr-EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2-4 times per year and serum...... cholesterol every second year. RESULTS: The patients (12 males/one female), age 56+/-9 (mean +/- SD) years, with a known duration of diabetes of 10+/-6 years, were followed for 55 (24-105) (median (range)) months. GFR decreased from 104 (50-126) to 80 (39-112) ml x min(-1) x 1.73 m(-2) (P = 0...

  13. Update on the Protective Renal Effects of Metformin in Diabetic Nephropathy.

    Science.gov (United States)

    Eisenreich, Andreas; Leppert, Ulrike

    2017-01-01

    Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy. The anti-diabetic drug metformin has been widely used for pharmacotherapeutic treatment of patients with diabetes mellitus. Besides its anti-diabetic actions, recent studies revealed additional nephroprotective effects of metformin in vitro and in vivo. Metformin was found to diminish apoptosis in different experimental renal settings. Moreover, it was shown to reduce albuminuria in diabetic rats as well as in patients with type 2 diabetes mellitus. These effects were demonstrated to be mediated via the AMPK/mTOR signaling axis. These data indicate beneficial and renoprotective effects of metformin in diabetic nephropathy. In this review, we will summarize the latest findings regarding the nephroprotective impact of metformin in vitro and in vivo. Moreover, we will depict and discuss the therapeutic potential of this drug for the treatment of diabetic nephropathy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Diabetic nephropathy: New insights into established therapeutic paradigms and novel molecular targets.

    Science.gov (United States)

    Sharma, Dilip; Bhattacharya, Pallab; Kalia, Kiran; Tiwari, Vinod

    2017-06-01

    Diabetic nephropathy is one of the most prevalent microvascular complication in patients suffering from diabetes and is reported to be the major cause of renal failure when compared to any other kidney disease. Currently, available therapies provide only symptomatic relief and unable to treat the underlying pathophysiology of diabetic nephropathy. This review will explore new insights into the established therapeutic paradigms targeting oxidative stress, inflammation and endoplasmic reticulum stress with the focus on recent clinical developments. Apart from this, the involvement of novel cellular and molecular mechanisms including the role of endothelin-receptor antagonists, Wnt signaling pathway, epigenetics and micro RNA is also discussed so that key molecular switches involved in the pathogenesis of diabetic nephropathy can be identified. Elucidating new molecular pathways will help in the development of novel therapeutics for the prevention and treatment of diabetic nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Type 1 Diabetes, Diabetic Nephropathy, and Pregnancy: A Systematic Review and Meta-Study

    Science.gov (United States)

    Piccoli, Giorgina B.; Clari, Roberta; Ghiotto, Sara; Castelluccia, Natascia; Colombi, Nicoletta; Mauro, Giuseppe; Tavassoli, Elisabetta; Melluzza, Carmela; Cabiddu, Gianfranca; Gernone, Giuseppe; Mongilardi, Elena; Ferraresi, Martina; Rolfo, Alessandro; Todros, Tullia

    2013-01-01

    BACKGROUND: In the last decade, significant improvements have been achieved in maternal-fetal and diabetic care which make pregnancy possible in an increasing number of type 1 diabetic women with end-organ damage. Optimal counseling is important to make the advancements available to the relevant patients and to ensure the safety of mother and child. A systematic review will help to provide a survey of the available methods and to promote optimal counseling. OBJECTIVES: To review the literature on diabetic nephropathy and pregnancy in type 1 diabetes. METHODS: Medline, Embase, and the Cochrane Library were scanned in November 2012 (MESH, Emtree, and free terms on pregnancy and diabetic nephropathy). Studies were selected that report on pregnancy outcomes in type 1 diabetic patients with diabetic nephropathy in 1980-2012 (i.e. since the detection of microalbuminuria). Case reports with less than 5 cases and reports on kidney grafts were excluded. Paper selection and data extraction were performed in duplicate and matched for consistency. As the relevant reports were highly heterogeneous, we decided to perform a narrative review, with discussions oriented towards the period of publication. RESULTS: Of the 1058 references considered, 34 fulfilled the selection criteria, and one was added from reference lists. The number of cases considered in the reports, which generally involved single-center studies, ranged from 5 to 311. The following issues were significant: (i) the evidence is scattered over many reports of differing format and involving small series (only 2 included over 100 patients), (ii) definitions are non-homogeneous, (iii) risks for pregnancy-related adverse events are increased (preterm delivery, caesarean section, perinatal death, and stillbirth) and do not substantially change over time, except for stillbirth (from over 10% to about 5%), (iv) the increase in risks with nephropathy progression needs confirmation in large homogeneous series, (v) the newly

  16. The study of association of Vitamin B12deficiency in type 2 diabetes mellitus with and without diabetic nephropathy in North Indian Population.

    Science.gov (United States)

    Bherwani, Sonny; Ahirwar, Ashok Kumar; Saumya, A S; Sandhya, A S; Prajapat, Brijesh; Patel, Sitendu; Jibhkate, Srushtee Bipin; Singh, Ritu; Ghotekar, L H

    2017-11-01

    Diabetic Mellitus is the chronic metabolic disorder associated with various complications of heart, eyes, nerves, kidney etc. Diabetic Nephropathy is one of the leading causes of death in diabetic patient. We hypothesized that decrease Vitamin B 12 levels is associated with Diabetic Nephropathy. Aim of our study is to study the serum Vitamin B 12 levels in type 2 diabetes mellitus patients with and without nephropathy. Our study population consist of 100 subjects out of which 50 cases of Diabetes Mellitus without Diabetic Nephropathy and 50 cases of Diabetes Mellitus with Diabetic Nephropathy. We measured various routine lab parameters, apart from it, we measured spot urinary albumin to creatinine ratio to assess diabetic nephropathy and in special investigation we measured serum Vitamin B 12 by chemiluminesence based immunoassay. Serum Vitamin B 12 level in the group with nephropathy (181.6±17.6pg/dl) was significantly lower than in the group without nephropathy (286±30.1pg/dl) (p=0.03). Our study points towards the decrease levels of serum Vitamin B 12 levels associated with the complication of diabetic mellitus such as diabetic nephropathy. So treatment of Vitamin B 12 deficiency by supplementing could prevent the development and progression of diabetic nephropathy and improves the overall management of diabetic patient. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  17. Association analysis of dyslipidemia-related genes in diabetic nephropathy.

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    Gareth J McKay

    Full Text Available Type 1 diabetes (T1D increases risk of the development of microvascular complications and cardiovascular disease (CVD. Dyslipidemia is a common risk factor in the pathogenesis of both CVD and diabetic nephropathy (DN, with CVD identified as the primary cause of death in patients with DN. In light of this commonality, we assessed single nucleotide polymorphisms (SNPs in thirty-seven key genetic loci previously associated with dyslipidemia in a T1D cohort using a case-control design. SNPs (n = 53 were genotyped using Sequenom in 1467 individuals with T1D (718 cases with proteinuric nephropathy and 749 controls without nephropathy i.e. normal albumin excretion. Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK to compare allele frequencies in cases and controls. In a sensitivity analysis, samples from control individuals with reduced renal function (estimated glomerular filtration rate<60 ml/min/1.73 m(2 were excluded. Correction for multiple testing was performed by permutation testing. A total of 1394 samples passed quality control filters. Following regression analysis adjusted by collection center, gender, duration of diabetes, and average HbA1c, two SNPs were significantly associated with DN. rs4420638 in the APOC1 region (odds ratio [OR] = 1.51; confidence intervals [CI]: 1.19-1.91; P = 0.001 and rs1532624 in CETP (OR = 0.82; CI: 0.69-0.99; P = 0.034; rs4420638 was also significantly associated in a sensitivity analysis (P = 0.016 together with rs7679 (P = 0.027. However, no association was significant following correction for multiple testing. Subgroup analysis of end-stage renal disease status failed to reveal any association. Our results suggest common variants associated with dyslipidemia are not strongly associated with DN in T1D among white individuals. Our findings, cannot entirely exclude these key genes which are central to the process of dyslipidemia, from

  18. 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.

  19. The screening for diabetic nephropathy in diabetes clinic in ...

    African Journals Online (AJOL)

    Study Design: Prospective cross- sectional study. Populations: during the period from Jan-March 2008, 98 diabetic patients with type 1 or type 2 were randomly selected from patients attending the outpatient diabetes clinic in Omdurman Teaching Hospital. Methodology: ninety eight adult type1 and 2 diabetic patients were ...

  20. Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy.

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    Xiaoyi Zheng

    Full Text Available Diabetic nephropathy (DN is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms that govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN at four weeks after induction of diabetes, but before histologic injury, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1, as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

  1. Baseline characteristics in PRIORITY study: Proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in type 2 diabetes

    DEFF Research Database (Denmark)

    Tofte, Nete

    into high-or low risk groups based on CKD273. Patients in the high risk group are assigned to spironolactone 25 mg once daily or placebo, whereas the low-risk group is followed on standard care. The trial continues until September 2018, following patients for up to 4.5 years. The primary endpoint......Background and aims The urinary proteomics based classifier CKD273 has been shown to retrospectively identify normoalbuminuric diabetic patients who progress to overt kidney disease. In the PRIORITY (Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early...... diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria) trial, the aim is to confirm that CKD273 can predict microalbuminuria prospectively, and to test whether mineralocorticoid receptor antagonism (MRA) delays progression to microalbuminuria. Here we report the association between CKD273...

  2. Is low birth weight a risk factor for the development of diabetic nephropathy in patients with type 1 diabetes?

    DEFF Research Database (Denmark)

    Eshoj, O; Vaag, A; Borch-Johnsen, K

    2002-01-01

    : The patients were identified from a population-based study of chronic diabetic complications in the Funen County, Denmark. MAIN OUTCOMES: Birth weights according to the presence of diabetic nephropathy. RESULTS: The median (10-90 percentile) birth weights were 3,600 g (2,960-4,274) in the group with diabetic......OBJECTIVES: To investigate if low birth weight as a consequence of intrauterine malnutrition is a risk factor for the later development of diabetic nephropathy. DESIGN AND SUBJECTS: In a case-control set-up a group of type 1 diabetic subjects with diabetic nephropathy (n = 51) and a matched control...... nephropathy and 3,600 g (2,880-4,220) in the group without nephropathy, P = 0.52. In the lower quartile of birth weights the median (10-90 percentile) birth weights were 3,000 g (2,780-3,200) in the group with nephropathy versus 2,850 g (2,250-3,175) in the group without nephropathy, P = 0.07. In the upper...

  3. Adenosine monophosphate–activated protein kinase in diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Yaeni Kim

    2016-06-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 5′ adenosine monophosphate–activated protein kinase (AMPK, an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

  4. Nephropathy in type 1 diabetes is associated with increased circulating activated platelets and platelet hyperreactivity

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Barnard, Marc R.

    2009-01-01

    -diabetic controls (P = 0.0075). There were no differences between groups in activated GPIIb/IIIa or in response to TRAP at any end-point. More patients with nephropathy received aspirin (71.4%) compared to normoalbuminuric patients (27.4%) (P ..., is associated with circulating activated platelets and platelet hyperreactivity to ADP, despite the confounding variable of more nephropathy patients receiving aspirin. This platelet activation is likely to contribute to the known increased risk of cardiovascular events in patients with diabetic nephropathy...

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

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    Bao-hai Zhang

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

  6. 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

  7. Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Andersen, S; Tarnow, L; Rossing, P

    2000-01-01

    and hemodynamic effects of specific intervention in the renin-angiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition. METHODS: A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 +/- 2 years (mean +/- SEM...... inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy....

  8. Prevalence and Risk Factors of Diabetic Nephropathy in Omani Type 2 Diabetics in Al-Dakhiliyah Region

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    Abdulhakeem Hamood Alrawahi

    2012-05-01

    Full Text Available Objective: To assess the prevalence and risk factors of diabetic nephropathy among Omani type 2 diabetics in Al-Dakhiliyah region of the Sultanate of Oman.Methods: A cross-sectional and a case control study designs were used to assess the prevalence and risk factors respectively. For the prevalence study a sample of 699 diabetic subjects were selected randomly from two polyclinics in Al-Dakhiliyah region; Sumail and Nizwa polyclinics. For the case control study, a sample consisting of 215 cases and 358 controls were randomly selected from those who were included in the cross-sectional study. A well designed questionnaire has been used to collect data regarding the disease and risk factors. Data was analyzed using SPSS19 statistical program.Results: Total prevalence of diabetic nephropathy was calculated as 42.5% (95% C.I: 38.83% - 46.15%. The difference in the prevalence in the two polyclinic catchment area was not significant. The prevalence was significantly higher among males (51.6% compared to females (36.5%. Crude analysis of the risk factors showed significant association between diabetic nephropathy and the following factors; male gender, decreased literacy, long duration of diabetes mellitus, hypertension, retinopathy, neuropathy, family history of diabetic nephropathy, poor glycemic control (high HbA1c, and hypertriglyceridemia. Multivariate analysis showed the following factors to be independent risk factors; male gender, decreased literacy, long duration of diabetes, family history of diabetic nephropathy and poor glycaemic control (high HbA1c.Conclusion: The prevalence of diabetic nephropathy in this study was 42.5% and the significant risk factors associated with it included male gender, decreased literacy, long duration of diabetes, family history of diabetic nephropathy and poor glycemic control (high HbA1c.

  9. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

    NARCIS (Netherlands)

    Brenner, BM; Cooper, ME; de Zeeuw, D; Keane, WF; Mitch, WE; Parving, HH; Remuzzi, G; Snapinn, SM; Zhang, ZX; Shahinfar, S

    2001-01-01

    Background Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We

  10. Connective tissue growth factor and bone morphogenetic proteins in diabetic nephropathy

    NARCIS (Netherlands)

    Nguyen, T.Q.

    2008-01-01

    Diabetes mellitus is a severe and rapidly growing problem in health care, accounting for approximately 150 million patients worldwide. Patients with diabetes are at increased risk to develop diabetic nephropathy, which is currently the most important cause of end-stage renal disease in large parts

  11. [Role of C-peptide in the pathogenesis of diabetic nephropathy].

    Science.gov (United States)

    Martina, Valentina; Maestroni, Anna; Maestroni, Silvia; Zerbini, Gianpaolo

    2010-01-01

    Insulin and C-peptide are secreted by pancreatic beta cells in equimolar amounts. Although C-peptide has long been believed to have no biological function, in recent years this molecule has been recognized as an independent hormone with a specific G-protein-coupled receptor. Recent evidence suggests that C-peptide may also have a specific nephroprotective effect, particularly in cases of diabetic nephropathy. In animal models of diabetes this beneficial effect has been repeatedly confirmed. Contradictory results have been obtained in humans: on the one hand it was shown that patients with diabetic nephropathy have lower plasma levels of C-peptide than patients with diabetes of similar duration and normal renal function; on the other hand it is also evident that patients affected by type 2 diabetes develop nephropathy even in the presence of high plasma levels of C-peptide, suggesting that in humans C-peptide is likely to have multifaceted activity. This review describes the different arguments supporting or contrasting the notion of C-peptide as a potential new therapy for diabetic nephropathy. It is possible that only a well performed, large-scale clinical study with careful evaluation of the positive and negative effects of C-peptide will finally clarify whether C-peptide reintegration in patients with type 1 diabetes is able to prevent the development and/or control the progression of diabetic nephropathy.

  12. Assessment value of serum 25-hydroxy-vitamin D content detection for patients with diabetic nephropathy

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    Jun Luo

    2016-05-01

    Full Text Available Objective: To study the assessment value of serum 25-hydroxy-vitamin D content detection for patients with diabetic nephropathy. Methods: Healthy subjects, patients with type 2 diabetes mellitus and patients with diabetic nephropathy were selected for study and enrolled in control group, diabetes group and diabetic nephropathy group respectively, and contents of 25-hydroxy-vitamin D, RAS molecules and chemokines in serum as well as contents of podocyte injury molecules in urine were detected. Results: Serum 25-hydroxy-vitamin D content as well as Nephrin, Podocin, CD2AP and α3β1 integrin contents in urine all showed the trend of diabetic nephropathy group diabetes group > control group, and contents of PRA, AngII, ALD, MCP-1, FKN, VCAM-1, ICAM-1, OPN and MIF in serum as well as contents of Nesmin in urine of patients with macroalbuminuria were significantly higher than those of patients with microalbuminuria. Conclusion: Serum 25-hydroxy-vitamin D content significantly decreases in patients with diabetic nephropathy, and it can also assess the activity of RAS system, the degree of inflammatory response and the degree of podocyte injury.

  13. PPARγ as a therapeutic target in diabetic nephropathy and other renal diseases.

    Science.gov (United States)

    Yang, Jichun; Zhou, Yunfeng; Guan, Youfei

    2012-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear transcription factor that regulates many important physiological processes including glucose and lipid metabolism, energy homeostasis, cell proliferation, inflammation, immunity and reproduction. The current review aims to summarize and discuss recent findings evaluating the protective effects of PPARγ against kidney diseases with a focus on diabetic nephropathy. We will also delineate the potential underlying mechanisms. PPARγ plays important roles in renal physiology and pathophysiology. Agonists of PPARγ exert protective effects against various kidney diseases including diabetic nephropathy, ischemic renal injury, IgA nephropathy, chemotherapy-associated kidney damage, polycystic kidney diseases and age-related kidney diseases via both systemic and renal actions. PPARγ agonists are effective in delaying and even preventing the progression of many renal diseases, especially diabetic nephropathy. PPARγ may represent a promising target for the treatment of renal diseases.

  14. Optimal dose of lisinopril for renoprotection in type 1 diabetic patients with diabetic nephropathy: a randomised crossover trial

    DEFF Research Database (Denmark)

    Schjoedt, K J; Astrup, A S; Persson, Frederik Ivar

    2009-01-01

    AIMS/HYPOTHESIS: The purpose of this study was to evaluate the optimal renoprotective effect of ultrahigh doses of lisinopril, as reflected by short-term changes in urinary albumin excretion rate (UAER), in type 1 diabetic patients with diabetic nephropathy. METHODS: At the Steno Diabetes Center......, 49 type 1 diabetic patients with diabetic nephropathy completed this double-masked randomised crossover trial consisting of an initial washout period followed by three treatment periods each lasting 2 months, where all patients received lisinopril 20, 40 and 60 mg once daily in randomised order...

  15. Incidence of diabetic nephropathy in Type 1 diabetic patients in Spain: 'Estudio Diamante'.

    Science.gov (United States)

    Esmatjes, E; De Alvaro, F

    2002-07-01

    To determine the prevalence and the incidence of diabetic nephropathy in Type 1 diabetes mellitus in Spain and to investigate the risk factors for the development of microalbuminuria. One thousand five hundred and two patients with Type 1 diabetes mellitus were prospectively followed in 15 hospital diabetes outpatient clinics in Spain. Blood pressure, body weight, HbA(1c), total cholesterol, HDL-cholesterol, triglycerides, plasma creatinine and urinary albumin excretion (UAE) were determined every 3-5 months. A total of 1225 patients (624 males and 601 females), age 30.7+/-9.3 years with diabetes duration of 14.1+/-9.1 years completed 4.3 (4.0-5.1) years of follow-up. At baseline 14.2 (95% CI 12.3-16.3)% of patients had microalbuminuria, 5.1 (3.9-6.4)% macroalbuminuria and 3.4 (2.5-4.6)% kidney failure. During follow-up the annual incidence of microalbuminuria was 2.7 (2.2-3.2)%. In a multiple logistic regression analysis the predictors of progression to microalbuminuria were initial UAE, HbA(1c), diabetes duration, smoking, and HDL-cholesterol diabetic nephropathy in Spain are comparable to data obtained in similar studies carried out in other countries. The development of microalbuminuria is associated not only with glycaemic control and hypertension, but also to the control of other risk factors such as dyslipaemia and smoking.

  16. Poly(Adenosine 5'-diphosphate-ribose) polymerase inhibition counteracts multiple manifestations of experimental type 1 diabetic nephropathy.

    Science.gov (United States)

    Drel, Viktor R; Xu, Weizheng; Zhang, Jie; Pavlov, Ivan A; Shevalye, Hanna; Slusher, Barbara; Obrosova, Irina G

    2009-12-01

    This study was aimed at evaluating the role for poly(ADP-ribose) polymerase (PARP) in early nephropathy associated with type 1 diabetes. Control and streptozotocin-diabetic rats were maintained with or without treatment with one of two structurally unrelated PARP inhibitors, 1,5-isoquinolinediol (ISO) and 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de] anthracen-3-one (GPI-15427), at 3 mg/kg(-1) x d(-1) ip and 30 mg/kg(-1) x d(-1), respectively, for 10 wk after the first 2 wk without treatment. PARP activity in the renal cortex was assessed by immunohistochemistry and Western blot analysis of poly(ADP-ribosyl)ated proteins. Variables of diabetic nephropathy in urine and renal cortex were evaluated by ELISA, Western blot analysis, immunohistochemistry, and colorimetry. Urinary albumin excretion was increased about 4-fold in diabetic rats, and this increase was prevented by ISO and GPI-15427. PARP inhibition counteracted diabetes-associated increase in poly(ADP-ribose) immunoreactivities in renal glomeruli and tubuli and poly(ADP-ribosyl)ated protein level. Renal concentrations of TGF-beta(1), vascular endothelial growth factor, endothelin-1, TNF-alpha, monocyte chemoattractant protein-1, lipid peroxidation products, and nitrotyrosine were increased in diabetic rats, and all these changes as well as an increase in urinary TNF-alpha excretion were completely or partially prevented by ISO and GPI-15427. PARP inhibition counteracted diabetes-induced up-regulation of endothelin (B) receptor, podocyte loss, accumulation of collagen-alpha1 (IY), periodic acid-Schiff-positive substances, fibronectin, and advanced glycation end-products in the renal cortex. In conclusion, PARP activation is implicated in multiple changes characteristic for early nephropathy associated with type 1 diabetes. These findings provide rationale for development and further studies of PARP inhibitors and PARP inhibitor-containing combination therapies.

  17. Mitochondria: A Novel Therapeutic Target in Diabetic Nephropathy.

    Science.gov (United States)

    Yang, Shikun; Han, Yachun; Liu, Jun; Song, Panai; Xu, Xiaoxuan; Zhao, Li; Hu, Chun; Xiao, Li; Liu, Fuyou; Zhang, Hao; Sun, Lin

    2017-01-01

    Diabetic nephropathy (DN) is an important diabetic microvascular complication, and it is becoming the leading cause of end-stage renal disease worldwide. Unfortunately, there are no effective therapies to treat established DN. Therefore, new therapeutic targets are urgently required. Accumulating studies indicate that mitochondrial dysfunction is central to the pathogenesis of DN, and therapies targeted mitochondria might effectively delay the progression of DN. A structured search of previously research literature about mitochondrial structure and function, mitochondrial DNA, mitochondrial biogenesis, mitochondrial dynamics change, mitophagy, mitochondrial ROS, mitochondrial apoptosis and therapies targeted mitochondria has been performed in several databases. 176 papers were included in this review, the results from these papers indicated that mitochondrial dysfunction is a pivotal issue for the development of DN, such as elevated oxidative stress induced by disorders of the mitochondrial respiratory chain complex and mitochondrial dynamic disorders, mutation of mitochondrial DNA, mitochondrial abnormal biogenesis, mitochondrial excessive fission, mitochondrial ROS overproduction. In addition, several therapeutic agents targeting the mitochondria (e.g mitochondrial ROS modulators, mitochondrial fragmentation inhibitors and mitochondrial biogenesis activators) have shown perfect therapeutic effect and security for DN. The finding of this review has further confirmed the vital role of mitochondrial dysfunction in the progression of DN, management strategies for recovering the normal mitochondrial function will offer potential novel therapeutic targets for DN. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Role of T Cells in Type 2 Diabetic Nephropathy

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    Chia-Chao Wu

    2011-01-01

    Full Text Available Type 2 diabetic nephropathy (DN is the most common cause of end-stage renal disease and is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Inflammation and activation of the immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Macrophage has been well recognized to play an important role in type 2 DN, leukocyte infiltration, and participated in process of DN, as was proposed recently. Th1, Th2, Th17, T reg, and cytotoxic T cells are involved in the development and progression of DN. The purpose of this review is to assemble current information concerning the role of T cells in the development and progression of type 2 DN. Specific emphasis is placed on the potential interaction and contribution of the T cells to renal damage. The therapeutic strategies involving T cells in the treatment of type 2 DN are also reviewed. Improving knowledge of the recognition of T cells as significant pathogenic mediators in DN reinforces the possibility of new potential therapeutic targets translated into future clinical treatments.

  19. The Emerging Roles of Microparticles in Diabetic Nephropathy.

    Science.gov (United States)

    Lu, Chen Chen; Ma, Kun Ling; Ruan, Xiong Zhong; Liu, Bi Cheng

    2017-01-01

    Microparticles (MPs) are a type of extracellular vesicles (EVs) shed from the outward budding of plasma membranes during cell apoptosis and/or activation. These microsized particles then release specific contents (e.g., lipids, proteins, microRNAs) which are active participants in a wide range of both physiological and pathological processes at the molecular level, e.g., coagulation and angiogenesis, inflammation, immune responses. Research limitations, such as confusing nomenclature and overlapping classification, have impeded our comprehension of these tiny molecules. Diabetic nephropathy (DN) is currently the greatest contributor to end-stage renal diseases (ESRD) worldwide, and its public health impact will continue to grow due to the persistent increase in the prevalence of diabetes mellitus (DM). MPs have recently been considered as potentially involved in DN onset and progression, and this review juxtaposes some of the research updates about the possible mechanisms from several relevant aspects and insights into the therapeutic perspectives of MPs in clinical management and pharmacological treatment of DN patients.

  20. Association of Serum Adropin Concentrations with Diabetic Nephropathy

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    Wenchao Hu

    2016-01-01

    Full Text Available Objective. Adropin is a newly identified regulatory protein encoded by the Enho gene and is critically involved in energy homeostasis and insulin sensitivity. This study aims to determine the correlation of serum adropin concentrations with diabetic nephropathy (DN. Methods. This study consisted of 245 patients with type 2 diabetes mellitus (T2DM and 81 healthy subjects. Then T2DM patients were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria subgroups based on urine albumin to creatinine ratio (ACR. Results. T2DM patients showed significantly lower serum adropin concentrations than those in the controls. T2DM patients with macroalbuminuria had significantly decreased serum adropin concentrations compared with the other three groups. In addition, T2DM patients with microalbuminuria showed lower serum adropin concentrations than those in patients with normoalbuminuria. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing T2DM and DN. Pearson correlation analysis indicated that serum adropin was negatively correlated with body mass index (BMI, blood urea nitrogen, creatinine, and ACR and positively correlated with glomerular filtration rate. Furthermore, multiple linear regression analysis showed that BMI and ACR were negatively correlated with serum adropin levels. Conclusion. Serum adropin concentrations are negatively associated with renal function. Adropin may be implicated in the pathogenesis of DN development.

  1. Predictive factors for non-diabetic nephropathy in diabetic patients. The utility of renal biopsy.

    Science.gov (United States)

    Bermejo, Sheila; Soler, María José; Gimeno, Javier; Barrios, Clara; Rodríguez, Eva; Mojal, Sergi; Pascual, Julio

    Diabetic renal lesions can only be diagnosed by kidney biopsy. These biopsies have a high prevalence of non-diabetic lesions. The aims of the study were to determine the predictability of non-diabetic nephropathy (NDN) in diabetics and study differences in survival and renal prognosis. In addition, we evaluated histological lesions and the effect of proteinuria on survival and renal prognosis in patients with diabetic nephropathy (DN). A descriptive, retrospective study of kidney biopsies of diabetics between 1990 and 2013 in our centre. 110 patients were included in the study: 87 men (79%), mean age 62 years (50-74), mean serum creatinine 2.6mg/dl (0.9-4.3) and proteinuria 3.5g/24hours (0.5-6.5). 61.8% showed NDN, 34.5% showed DN and 3,6% showed DN+NDN. The most common NDN was IgA nephropathy (13,2%). In the multivariate analysis, creatinine (OR: 1.48, 1.011-2.172, p=0.044), proteinuria/24hours (OR: 0.813, 0.679-0.974, p=0.025), duration of diabetes (OR: 0.992, 0.987-0.998, p=0.004), age (OR: 1.068, 95% CI: 1.010-1.129, p=0.022), and diabetic retinopathy (OR: 0.23, 0.066-0.808, p=0.022) were independently associated with NDN. We did not find any differences in survival or renal prognosis. Concerning patients with DN, increased nodular mesangial expansion (p=0.02) and worse renal prognosis (p=0.004) were observed in nephrotic proteinuria as compared to non-nephrotic proteinuria. We did not find differences in patient survival. The most common cause of NDN was IgA nephropathy. Higher creatinine levels, shorter duration of diabetes, absence of diabetic retinopathy, lower proteinuria, and older age were risk factors for NDN. Patients with DN and nephrotic-range proteinuria had worse renal prognosis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy.

    Science.gov (United States)

    Ma, Jin; Chadban, Steven J; Zhao, Cathy Y; Chen, Xiaochen; Kwan, Tony; Panchapakesan, Usha; Pollock, Carol A; Wu, Huiling

    2014-01-01

    Toll like receptor (TLR) 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ) diabetes. Subsequently, we demonstrated that TLR4-/- mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA) and expression of fibrogenic genes (TGF-β and fibronectin) were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.

  3. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Jin Ma

    Full Text Available Toll like receptor (TLR 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ diabetes. Subsequently, we demonstrated that TLR4-/- mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA and expression of fibrogenic genes (TGF-β and fibronectin were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.

  4. Determinants of diabetic nephropathy in Ayder Referral Hospital, Northern Ethiopia: A case-control study.

    Science.gov (United States)

    Hintsa, Solomon; Dube, Lamessa; Abay, Mebrahtu; Angesom, Teklit; Workicho, Abdulhalik

    2017-01-01

    Diabetic nephropathy is the most serious complication of diabetes which leads to end-stage renal failure and other complication of diabetes mellitus. Determinants of Diabetic nephropathy are not consistent in different studies and associated factors to chronic complications of diabetes are not specific and there are limited studies specific to diabetic nephropathy. Thus, the aim of this study is to identify determinants of diabetic nephropathy in Ayder Referral Hospital, Northern Ethiopia. A case-control study was conducted from February 14 to May 8 2016. Diabetic patients who developed nephropathy in the last two years were the cases and diabetic patients free of nephropathy were controls. Cases and controls were identified detailed review of the chronic care follow up chart. Then simple random sampling was used to select sample of 420 (with control to case ratio of 4:1) resulting in 84 cases and 336 controls. Record review and interviewer administered questionnaire were used to collect data. Data was coded and entered in to Epi-Data version 3.1 and then exported to STATA 12 for analysis. Variables with P-valuesdiabetic nephropathy. OR was calculated with 95% CI to show strength of association. The mean age (±Standard deviation) for the cases and the controls were 52(SD: ±1.34) and 42.4(SD: ±0.8) respectively. In multiple logistic regressions age of patient (AOR: 1.037 95%CI: 1.01-1.064), duration of diabetes after diagnosis (AOR for one year increase: 1.09 95%CI: 1.036-1.15), not-adhered to blood glucose measurement at home (AOR: 6.81 95%CI: 1.15-40.24), having Systolic Hypertension (AOR;2.13 (1.002-4.51), poor glycemic control (AOR;2.71 95%CI: (1.49-4.95), being overweight(AOR;2.7(1.47-4.96) were the independent predictors of diabetic nephropathy. In the light of these findings, targeted interventions should be designed at the follow up clinic to address the risk of developing diabetic nephropathy among the risk groups.

  5. Benefits of long-term antihypertensive treatment on prognosis in diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Jacobsen, P; Rossing, K

    1996-01-01

    We assessed the prognosis of diabetic nephropathy during long-term antihypertensive treatment as compared to the prognosis during the natural history of this complication in a prospective study of all IDDM patients (N = 45) aged under 50 with onset of diabetes before the age of 31 who developed...... diabetic nephropathy between 1974 and 1978 at Steno Diabetes Center, and were followed until death or for at least 16 years [median 16 (4 to 21) years]. Antihypertensive treatment was started 3 (0 to 13) years after onset of diabetic nephropathy. Mean arterial blood pressure at start of antihypertensive...... treatment was 148/96 (sd 12/10) mm Hg and 143/86 (16/6) mm Hg during the whole interval of antihypertensive treatment (P

  6. Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Jensen, C

    2000-01-01

    , randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter. The study included 51 hypertensive type 1 diabetic patients with diabetic nephropathy. Three patients......OBJECTIVE: To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed a 4-year prospective......). Two patients in the lisinopril group and three patients in the nisoldipine group entered therapy for end-stage renal failure. CONCLUSIONS: Long-term treatment with lisinopril or nisoldipine has similar beneficial effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients....

  7. The prevalence of diabetic nephropathy in adult patients with insulin dependent diabetes mellitus attending Parirenyatwa Diabetic Clinic, Harare.

    Science.gov (United States)

    Mafundikwa, A; Ndhlovu, C E; Gomo, Zar

    2007-01-01

    The objective of this study was to determine the prevalence of diabetic nephropathy in a diabetic clinic in a tertiary hospital setting in Zimbabwe. Descriptive cross sectional study. Diabetic clinic in a tertiary hospital. 75 insulin dependent diabetic consenting adults aged over 18 years. Consecutive sampling of 75 insulin dependent consenting subjects presenting at the Parirenyatwa Diabetic Clinic was conducted over a four month period. Patients were tested for proteinuria using dipsticks and were divided into dipstick positive and dipstick negative. The dipstick positive samples were sent to the laboratory for protein quantification. The dipstick negative samples were tested for microalbuminuria. Urine albumin creatinine ratios were utilised to quantify the proteinuria. Prevalence of overt proteinuria and the prevalence of microalbuminuria. Overt proteinuria was found in 16 (21%) patients. Microalbuminuria was found in 9 (12%) of the patients. Nephropathy was, therefore, found in 25 (33%). There is a high prevalence of diabetic nephropathy in adult patients with insulin dependent diabetis mellitus attending Parirenyatwa Diabetic Clinic.

  8. Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats.

    Directory of Open Access Journals (Sweden)

    TingTing Zhao

    Full Text Available Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF, a traditional Chinese medicine, on DN.Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined.We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα, chemokine (MCP-1, and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7.The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.

  9. Markers of Diabetic Nephropathy in Diabetic Patients in Gusau ...

    African Journals Online (AJOL)

    the contrary, in type II diabetics hyperglycemia starts after the forties, usually when the kidneys have already suffered the long term consequences of aging, and of other recognized promoters of chronic renal injury such as arterial hypertension, obesity, dyslipidaemia, and smoking (Ruggenet and Rumuzzi 1998). Both type I.

  10. nephropathy

    Directory of Open Access Journals (Sweden)

    Wen-ming YUAN

    2017-10-01

    Full Text Available Objective To evaluate the diagnostic significance of PLA2R and IgG4 in elderly patients with idiopathic membranous nephropathy (IMN. Methods The clinical data were retrospectively analyzed of patients with IMN (49 males and 49 females, aged 66.6±5.4 years or Non-IMN (57 males and 41 females, aged 67.1±6.5 years who were admitted in the authors served Department of Nephrology from Apr. 2014 to Feb. 2016 and accepted renal biopsy. SPSS13.0 was employed to evaluate the sensitivity, specificity and calculate the area under ROC curve (AUC of serum anti-PLA2R antibody, glomerular PLA2R and IgG1-4 subclasses on diagnosing IMN. Results On diagnosing IMN, the sensitivity and specificity of serum anti-PLA2R antibody were 77.6% and 89.8% [AUC=0.869(0.816-0.923], of glomerular PLA2R were 66.3% and 94.9% [AUC=0.805(0.741- 0.87], and of glomerular IgG1-IgG4 were 80.6% and 78.6%, 60.2% and 83.7%, 41.8% and 84.7%, and 93.9% and 89.8%, respectively [AUC=0.767(0.696-0.838, 0.709(0.635-0.783, 0.628(0.549-0.706 and 0.94(0.901-0.978, respectively]. As to the combined use of glomerular PLA2R and IgG4 on diagnosing IMN, the sensitivity was 93.9% when either one of glomerular PLA2R and IgG4 was positive, or the specificity was 96.9% when both glomerular PLA2R and IgG4 were positive. Conclusion PLA2R and IgG4 can effectively serve the diagnosis of IMN, and the combined use of PLA2R and IgG4 may be better than single indicator alone. DOI: 10.11855/j.issn.0577-7402.2017.09.11

  11. Mice Deficient in PAPP-A Show Resistance to the Development of Diabetic Nephropathy

    Science.gov (United States)

    Mader, Jessica R.; Resch, Zachary T.; McLean, Gary R.; Mikkelsen, Jakob H.; Oxvig, Claus; Marler, Ronald J.; Conover, Cheryl A.

    2013-01-01

    We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old wild-type (WT) and PAPP-A knock-out (KO) mice. Renal histopathology was evaluated after four months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman’s capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration as diabetic WT mice indicating that these changes were predominantly age-related. However, thickened Bowman’s capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic PAPP-A KO mice had significantly reduced or no evidence of changes in Bowman’s capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT compared to PAPP-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy. PMID:23881937

  12. Diabetic nephropathy and its risk factors in a society with a type 2 diabetes epidemic: a Saudi National Diabetes Registry-based study.

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    Khalid Al-Rubeaan

    Full Text Available AIMS: The prevalence of diabetic nephropathy and its risk factors have not been studied in a society known to have diabetes epidemic like Saudi Arabia. Using a large data base registry will provide a better understanding and accurate assessment of this chronic complication and its related risk factors. METHODOLOGY: A total of 54,670 patients with type 2 diabetes aged ≥ 25 years were selected from the Saudi National Diabetes Registry (SNDR and analyzed for the presence of diabetic nephropathy. The American Diabetes Association (ADA criterion was used to identify cases with microalbuminuria, macroalbuminuria and end stage renal disease (ESRD for prevalence estimation and risk factor assessment. RESULTS: The overall prevalence of diabetic nephropathy was 10.8%, divided into 1.2% microalbuminuria, 8.1%macroalbuninuria and 1.5% ESRD. Age and diabetes duration as important risk factors have a strong impact on the prevalence of diabetic nephropathy, ranging from 3.7% in patients aged 25-44 years and a duration of >5 years, to 21.8% in patients ≥ 65 years with a diabetes duration of ≥ 15 years. Diabetes duration, retinopathy, neuropathy, hypertension, age >45 years, hyperlipidemia, male gender, smoking, and chronologically, poor glycemic control has a significantly high risk for diabetic nephropathy. CONCLUSION: The prevalence of diabetic nephropathy is underestimated as a result of a shortage of screening programs. Risk factors related to diabetic nephropathy in this society are similar to other societies. There is thus an urgent need for screening and prevention programs for diabetic nephropathy among the Saudi population.

  13. 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, David-Alexandre; Groop, Per-Henrik; McGinn, Steven

    2008-01-01

    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....

  14. Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

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

    1984-01-01

    The effect of acute lowering of arterial blood pressure upon kidney function in nephropathy was studied in 13 patients with long-term Type 1 (insulin-dependent) diabetes. Ten normal subjects (six normotensive and four hypertensive) and five short-term Type 1 diabetic patients without nephropathy...... micrograms) or saline (0.154 mmol/l). The arterial blood pressure was similar in the diabetic patients with nephropathy (mean 136 +/- 11 divided by 88 +/- mmHg) and in the non-diabetic control subjects (mean 140 +/- 25 divided by 92 +/- 15 mmHg). The clonidine injection induced similar reductions in mean...... arterial blood pressure in all three groups (16-18 mmHg). While glomerular filtration rate and urinary albumin excretion rate remained unchanged in both control groups after clonidine injection, glomerular filtration rate diminished from 78 to 71 ml/min per 1.73 m2 (p les than 0.01), and urinary albumin...

  15. Time course of the antiproteinuric and antihypertensive effect of losartan in diabetic nephropathy

    DEFF Research Database (Denmark)

    Andersen, Steen; Jacobsen, Peter; Tarnow, Lise

    2003-01-01

    is unknown. We evaluated the time course of the antihypertensive and antialbuminuric effect after initiation of AT1 receptor blockade by losartan in diabetic nephropathy. METHODS: Ten hypertensive type 1 diabetic patients with diabetic nephropathy were included in the study. After a washout period of 4 weeks......, patients received losartan 100 mg once daily for 28 days. Every morning, one urine sample was collected for daily determination of albumin/creatinine ratio. Twenty-four hour blood pressure (Takeda TM2420), plasma renin and plasma creatinine were measured at baseline and days 7, 14 and 28. RESULTS: Baseline...... of losartan treatment and stabilized after 7 days (P

  16. The Search for Molecular Prognostic Markers of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

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    V. M. Ibragimov

    2016-03-01

    Full Text Available The purpose of this study was to search for molecular prognostic markers of diabetic nephropathy (DN in patients with type 2 diabetes mellitus (T2DM. The study included 205 patients with T2DM and DN (stages 1 to 4. All patients were stratified by the MDRD equation. The control group included 30 healthy individuals. All T2DM patients were divided into 4 groups depending on the DN stages. Group 1 included 42 patients with DN-Stage 1 (prenephropathy, Group 2 included 48 patients with DN-Stage 2 (incipient nephropathy; Group 3 included 65 patients with DN-Stage 3 (overt nephropathy, and Group 4 included 50 patients with DN-Stage 4 (kidney failure. Molecular phenotyping of urine was processed with methods of proteomics: the prefractionation, the separation of proteins with standard sets (MB-HIC C8 Kit, MB-IMAC Cu, MB-Wax Kit, «Bruker», USA, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS/MS, Ultraflex II, «Bruker», USA. The data of the molecular interactions and functional features of proteins were received with STRING 10.0 database. Potentially new molecular markers of DN development were identified. The research into signaling pathways and the molecules that are involved in ECM formation may help in developing strategies to prevent DN.

  17. Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hommel, E; Andersen, P; Gall, M A

    1992-01-01

    The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol greater than or equal to 5.5 mmol/l) Type 1 ...

  18. Association between CNDP1 genotype and diabetic nephropathy is sex specific

    NARCIS (Netherlands)

    Mooyaart, Antien L.; Zutinic, Ana; Bakker, Stephan J. L.; Grootendorst, Diana C.; Kleefstra, Nanne; van Valkengoed, Irene G. M.; Böhringer, Stefan; Bilo, Henk J. G.; Dekker, Friedo W.; Bruijn, Jan Anthonie; Navis, Gerjan; Janssen, Bart; Baelde, Hans J.; de Heer, Emile

    2010-01-01

    OBJECTIVE: The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. RESEARCH DESIGN AND METHODS: Three separate groups of 114, 90, and 66

  19. Association Between CNDP1 Genotype and Diabetic Nephropathy Is Sex Specific

    NARCIS (Netherlands)

    Mooyaart, Antien L.; Zutinic, Ana; Bakker, Stephan J. L.; Grootendorst, Diana C.; Kleefstra, Nanne; van Valkengoed, Irene G. M.; Bohringer, Stefan; Bilo, Henk J. G.; Dekker, Friedo W.; Bruijn, Jan Anthonie; Navis, Gerjan; Janssen, Bart; Baelde, Hans J.; De Heer, Emile

    OBJECTIVE-The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. RESEARCH DESIGN AND METHODS-Three separate groups of 114, 90, and 66

  20. The role of CTGF in diabetic nephropathy : Marker, pathogenic factor and target for therapeutic intervention

    NARCIS (Netherlands)

    Roestenberg, Patricia Maria Henrica

    2007-01-01

    Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and a major cause of end stage renal disease. DN is a progressive fibrotic kidney disease that is structurally characterized by mesangial matrix accumulation and thickening of the glomerular basement membrane (GBM), and

  1. Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Rossing, P; Tarnow, L

    1995-01-01

    Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0...

  2. Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Sato, A; Ali, S

    1999-01-01

    hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo...

  3. Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats

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    Tian W

    2015-09-01

    Full Text Available Wenjie Tian,1,2,* Hongen Lei,1,* Ruili Guan,1 Yongde Xu,1 Huixi Li,1 Lin Wang,1 Bicheng Yang,1 Zhezhu Gao,1 Zhongcheng Xin1 1Andrology Center, Peking University First Hospital, Peking University, Beijing, 2Department of Urology, The Second Hospital of Jilin University, Jilin University, Changchun, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II on reversing diabetic nephropathy in streptozotocin (STZ-induced type I diabetic rats.Methods: Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU for tracking endogenous label retaining progenitor cells (LRCs. At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16, diabetes mellitus group (DM; n=16, and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16. Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor-β/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-β/Smad/CTGF signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues.Results: Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-β/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney.Conclusion: ICA

  4. Carnosine as a protective factor in diabetic nephropathy - Association with a leucine repeat of the carnosinase gene CNDP1

    NARCIS (Netherlands)

    Janssen, B; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, Stephan; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Koppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J.

    The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development

  5. The Concept and the Epidemiology of Diabetic Nephropathy Have Changed in Recent Years

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    Alberto Martínez-Castelao

    2015-05-01

    Full Text Available Diabetes Mellitus (DM is a growing worldwide epidemic. It was estimated that more than 366 million people would be affected. DM has spread its presence over the world due to lifestyle changes, increasing obesity and ethnicities, among others. Diabetic nephropathy (DN is one of the most important DM complications. A changing concept has been introduced from the classical DN to diabetic chronic kidney disease (DCKD, taking into account that histological kidney lesions may vary from the nodular or diffuse glomerulosclerosis to tubulointerstitial and/or vascular lesions. Recent data showed how primary and secondary prevention were the key to reduce cardiovascular episodes and improve life expectancy in diabetic patients. A stabilization in the rate of end stage kidney disease has been observed in some countries, probably due to the increased awareness by primary care physicians about the prognostic importance of chronic kidney disease (CKD, better control of blood pressure and glycaemia and the implementation of protocols and clinical practice recommendations about the detection, prevention and treatment of CKD in a coordinated and multidisciplinary management of the DM patient. Early detection of DM and DCKD is crucial to reduce morbidity, mortality and the social and economic impact of DM burden in this population.

  6. The role of hypertension in the development of nephropathy in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

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

    1990-01-01

    Which comes first when developing clinical diabetic nephropathy, the blood pressure rise or the increasing urinary albumin excretion? This issue is discussed based on recent literature of studies in humans with Type 1 (insulin-dependent) diabetes mellitus. We conclude that hypertension has...... a central role in the progression of diabetic nephropathy and has deleterious effects on the life expectancy of patients who already have signs of diabetic renal disease in terms of elevated urinary albumin excretion. However, blood pressure is preceded by small increments of urinary albumin excretion rates......, an indicator of universally increased vascular leakiness, and thus does not seem to be the cause of diabetic nephropathy....

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

    Science.gov (United States)

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

    2015-04-01

    Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension and progressive renal insufficiency. The aim of this study was to investigate the effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats. Streptozotocin (STZ) diabetic rats were orally treated with three doses (50, 100 and 200 mg/kg) of strawberry leaf extract for 30 days. Nephropathy biomarkers in plasma and kidney were examined at the end of the experiment. The three doses of strawberry leaf extract significantly decreased the levels of blood glucose, urea nitrogen, plasma creatinine, kidney injury molecule (Kim)-1, renal malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), interleukin (IL)- 6 and caspase-3 in diabetic rats. Meanwhile, the levels of plasma insulin, albumin, uric acid, renal catalase (CAT), superoxide dismutase (SOD) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in diabetic rats treated with strawberry leaf extract. These results indicate the role of strawberry leaves extract as anti-diabetic, antioxidant, anti-inflammatory and anti-apoptosis in diabetic nephropathy. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

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

    Science.gov (United States)

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

    2015-01-01

    Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension and progressive renal insufficiency. The aim of this study was to investigate the effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats. Streptozotocin (STZ) diabetic rats were orally treated with three doses (50, 100 and 200 mg/kg) of strawberry leaf extract for 30 days. Nephropathy biomarkers in plasma and kidney were examined at the end of the experiment. The three doses of strawberry leaf extract significantly decreased the levels of blood glucose, urea nitrogen, plasma creatinine, kidney injury molecule (Kim)-1, renal malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), interleukin (IL)- 6 and caspase-3 in diabetic rats. Meanwhile, the levels of plasma insulin, albumin, uric acid, renal catalase (CAT), superoxide dismutase (SOD) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in diabetic rats treated with strawberry leaf extract. These results indicate the role of strawberry leaves extract as anti-diabetic, antioxidant, anti-inflammatory and anti-apoptosis in diabetic nephropathy. PMID:25645466

  9. Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

    DEFF Research Database (Denmark)

    Fagerudd, J A; Tarnow, L; Jacobsen, P

    1998-01-01

    of hypertension in this group. However, the difference in prevalence of parental hypertension was not evident using office blood pressure measurements (64 vs. 57%; NS; difference 7% [-5.8-20%). Furthermore, patients with DN+ and with antihypertensive therapy in both parents were themselves more frequently treated......Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN......+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion pressure (SpaceLabs 90207) > or = 135/85 mm...

  10. 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 ...

  11. Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy.

    Directory of Open Access Journals (Sweden)

    Yongsoo Park

    Full Text Available Diabetic nephropathy (DN is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression in these patients.Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT and superoxide dismutase (SOD, potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs, which are important constituents of renal glomeruli.Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction.The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN.

  12. 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.

  13. Microvascular disease: what does the UKPDS tell us about diabetic nephropathy?

    Science.gov (United States)

    Bilous, R

    2008-08-01

    The UK Prospective Diabetes Study is the largest study in Type 2 diabetes with pre-specified renal outcomes. The study showed that the natural history of nephropathy in newly diagnosed Type 2 diabetic patients was similar to that described previously in those with Type 1 diabetes. Around 2% per annum progress from normo- to micro-albuminuria [urinary albumin concentration (UAC) > 50 mg/l] and a further 2% from microalbuminuria to clinical grade proteinuria (UAC > 300 mg/l). Mortality rates for those with nephropathy are high, increasing from 1.4% per annum (normoalbuminuria) to 4.6% per annum (clinical grade proteinuria), and to 19.2% per annum for those with renal impairment. More intensive blood glucose control resulted in both a 33% reduction in relative risk of development of microalbuminuria or clinical grade proteinuria at 12 years, and a significant reduction in the proportion doubling their plasma creatinine (0.91 vs. 3.52%, P = 0.0028). Tighter blood pressure control also reduced microalbuminuria and clinical grade proteinuria; but at 6 years there was no effect on plasma creatinine levels. These data underline the importance of glycaemic and blood pressure control in Type 2 diabetes in order to prevent diabetic nephropathy. Those patients unlucky enough to develop nephropathy need intensive surveillance and correction of cardiovascular risk factors.

  14. Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy

    DEFF Research Database (Denmark)

    Myrup, B; de Maat, M; Rossing, P

    1996-01-01

    Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C-reactive pro......Insulin-dependent diabetic patients with nephropathy have a high risk of cardiovascular disease. Chronic inflammation is a part of the pathogenesis of atherosclerosis, and presently we have studied the relation between the inflammatory state, measured as levels of interleukin-6 and C...

  15. [Oxalate nephropathy: a new entity of acute kidney injury in diabetic patients?].

    Science.gov (United States)

    Muji, A; Moll, S; Saudan, P

    2015-02-25

    Acute oxalate nephropathy is a severe cause of acute kidney injury characterized by tubule-interstitial oxalate deposits with an inflammatory infiltrate. Three cases of AKI occuring in diabetic patients, and whose renal biopsy gave a diagnosis of acute oxalate nephropathy are reported. This cristal deposit AKI is due to either primary hyperoxaluria or secondary to enteric hyperabsorption. Its prognosis is dismal and rapid recognition by renal biopsy and determination of the cause of hyperoxaluria is mandatory in order to avoid end-stage kidney disease. This diagnosis should be suspected in cases of non resolving AKI, especially in diabetic patients who may have undetected pancreatic exocrine insufficiency.

  16. The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Mahiro Kurashige

    Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

  17. 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.

  18. Adipocytokine zinc α2 glycoprotein (ZAG) as a novel urinary biomarker for normo-albuminuric diabetic nephropathy.

    Science.gov (United States)

    Lim, S C; Liying, D Q; Toy, W C; Wong, M; Yeoh, L Y; Tan, C; Lau, D; Tan, C; Subramaniam, T; Sum, C F

    2012-07-01

    A substantial proportion of diabetic nephropathy individuals are non-albuminuric. Using a proteomic approach, we searched for novel urinary biomarkers. We studied three groups (n = 6 per group) of males with Type 2 diabetes: (1) normal renal function; (2) classical diabetic nephropathy (urinary albumin-creatinine ratio > 1000 mg/g and glomerular filtration rate 2.5-fold, P < 0.05). In the non-albuminuric subjects, in addition to previously reported α(1) -microglobulin, the next most interesting spot (upregulated 3.44-fold, P = 0.0026) was human zinc-α(2) -glycoprotein, a novel adipose-cytokine associated with glomerular injury. This was confirmed by western blot and replicated in female diabetic nephropathy subjects. From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  19. RAGE-Aptamer Blocks the Development and Progression of Experimental Diabetic Nephropathy.

    Science.gov (United States)

    Matsui, Takanori; Higashimoto, Yuichiro; Nishino, Yuri; Nakamura, Nobutaka; Fukami, Kei; Yamagishi, Sho-Ichi

    2017-06-01

    The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) plays a central role in diabetic nephropathy. We screened DNA aptamers directed against RAGE (RAGE-aptamers) in vitro and examined the effects on the development and progression of diabetic nephropathy in streptozotocin-induced diabetic rats. RAGE-aptamer bound to RAGE with a K d of 5.68 nmol/L and resultantly blocked the binding of AGEs to RAGE. When diabetic rats received continuous intraperitoneal injection of RAGE-aptamer from week 7 to 11 of diabetes, the increases in renal NADPH oxidase activity, oxidative stress generation, AGE, RAGE, inflammatory and fibrotic gene and protein levels, macrophage and extracellular matrix accumulation, and albuminuria were significantly suppressed, which were associated with improvement of podocyte damage. Two-week infusion of RAGE-aptamer just after the induction of diabetes also inhibited the AGE-RAGE-oxidative stress system and MCP-1 levels in the kidneys of 8-week-old diabetic rats and simultaneously ameliorated podocyte injury and albuminuria. Moreover, RAGE-aptamer significantly suppressed the AGE-induced oxidative stress generation and inflammatory and fibrotic reactions in human cultured mesangial cells. The findings suggest that continuous infusion of RAGE-aptamer could attenuate the development and progression of experimental diabetic nephropathy by blocking the AGE-RAGE axis. © 2017 by the American Diabetes Association.

  20. Oral contraceptives, angiotensin-dependent renal vasoconstriction, and risk of diabetic nephropathy

    DEFF Research Database (Denmark)

    Ahmed, Sofia B; Hovind, Peter; Parving, Hans-Henrik

    2005-01-01

    OBJECTIVE: Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic...... kidney are unclear. RESEARCH DESIGN AND METHODS: Renal plasma flow (RPF) response to captopril, as an index of RAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we...... examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1-24). RESULTS: Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    in oxidative stress, inflammation, and fibrosis, in association with decreased extracellular matrix production. These findings demonstrate that monotherapy of Compound 21 is protective against the progression of experimental diabetic nephropathy by inhibiting renal oxidative stress, inflammation, and fibrosis.......The hemodynamic and nonhemodynamic effects of angiotensin II on diabetic complications are considered to be primarily mediated by the angiotensin II type 1 receptor subtype. However, its biological and functional effect mediated through the angiotensin II type 2 receptor subtype is still unclear...... model of type 1 diabetic nephropathy. Compound 21 treatment significantly attenuated diabetes mellitus-induced elevated levels of cystatin C, albuminuria, mesangial expansion, and glomerulosclerosis in diabetic mice. Moreover, Compound 21 markedly inhibited the expression of various proteins implicated...

  2. Promotion, prediction and prevention of progression of nephropathy in type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Rossing, P

    1998-01-01

    The scope of the present review is to discuss the prognosis of diabetic renal disease, putative progression promoters and the possibilities for treatment and prediction of treatment efficacy. The recent changes in the incidence of diabetic nephropathy in Type 1 diabetes mellitus are discussed....... Promoters of progression in diabetic nephropathy are evaluated, in particular arterial blood pressure, glycaemic control, albuminuria and cholesterol levels. Potential treatment modalities are discussed, with special focus on antihypertensive therapy, including a discussion of a specific renoprotective...... action of certain antihypertensive agents. Furthermore putative predictors of treatment efficacy are evaluated, demonstrating that the ability to lower the urinary albumin excretion rate after onset of treatment heralds a slow progression of the renal disease. The prognosis in diabetic renal disease has...

  3. Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Lajer, M.; Tarnow, L.; Jorsal, A.

    2008-01-01

    performed a prospective observational follow-up study including 397 type 1 diabetic patients with overt diabetic nephropathy (243 men aged 42.1 +/- 10.5 years, GFR 76 +/- 34 ml/min per 1.73 m(2)) and a control group of 175 patients with longstanding type 1 diabetes and persistent normoalbuminuria (104 men......OBJECTIVE: To investigate whether circulating asymmetric dimethylarginine (ADMA) levels are predictive of cardiovascular events, decline in glomerular filtration rate (GFR), end-stage renal disease (ESRD), and all-cause mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We...... aged 42.7 +/- 9.7 years, duration of diabetes 27.7 +/- 8.3 years). Patients were followed for a median 11.3 years (range 0.0-12.9) with yearly measurements of GFR ((51)Cr-EDTA plasma clearance) in patients with diabetic nephropathy. Endpoints were fatal and nonfatal cardiovascular disease (CVD...

  4. Comparative evaluation of torasemide and furosemide on rats with streptozotocin-induced diabetic nephropathy.

    Science.gov (United States)

    Arumugam, Somasundaram; Sreedhar, Remya; Miyashita, Shizuka; Karuppagounder, Vengadeshprabhu; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Pitchaimani, Vigneshwaran; Afrin, Rejina; Harima, Meilei; Suzuki, Kenji; Watanabe, Kenichi

    2014-08-01

    Nephropathy is one of the complications of diabetes mellitus in human and experimental animals. There are various pathological renal remodeling processes leading to diabetic nephropathy because of the chronic hyperglycemia during diabetes mellitus. Various reports suggest the involvement of oxidative stress, inflammation and fibrosis during this progression. As antihypertensive drugs are reported to provide renoprotection in various animal models and clinical studies, we have carried out this study to identify the effect of torasemide, a loop diuretic, against streptozotocin-induced diabetic nephropathy and compare with furosemide. Here we have performed the measurement of blood and urine parameters and renal protein expression levels for measuring the disease severity in streptozotocin-induced diabetic rats treated torasemide or furosemide and compared with the vehicle treated rats. Furosemide treatment significantly increased the urinary protein excretion when compared with the normal rats. Torasemide treatment has reduced the expression of mineralocorticoid receptor and oxidative stress marker p67phox levels with improved mRNA levels of heme oxygenase-1 in the kidneys. In addition, torasemide treated diabetic rats showed significantly reduced expression of renal fibrosis related proteins when compared with the vehicle treated diabetic rats. Although furosemide treatment has produced improvement, its effects are comparably less than that of torasemide. Thus with the present results, we can suggest that torasemide treatment can improve the diabetic kidney disease in this rat model and which is superior to furosemide against renal fibrotic remodeling. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. TRAIL Deficiency Contributes to Diabetic Nephropathy in Fat-Fed ApoE-/- Mice

    Science.gov (United States)

    Cartland, Siân P.; Erlich, Jonathan H.; Kavurma, Mary M.

    2014-01-01

    Background We recently demonstrated that TNF-related apoptosis-inducing ligand (TRAIL) is protective of diet-induced diabetes in mice. While TRAIL has been implicated in chronic kidney disease, its role in vivo in diabetic nephropathy is not clear. The present study investigated the role of TRAIL in the pathogenesis of diabetic nephropathy using TRAIL-/-ApoE-/- mice. Methods TRAIL-/-ApoE-/- and ApoE-/- mice were fed a high fat diet for 20 w. Plasma glucose and insulin levels were assessed over 0, 5, 8 and 20 w. At 20 w, markers of kidney function including creatinine, phosphate, calcium and cystatin C were measured. Changes in mRNA expression of MMPs, TIMP-1, IL-1β and IL-18 were assessed in the kidney. Functional and histological changes in kidneys were examined. Glucose and insulin tolerance tests were performed. Results TRAIL-/-ApoE-/- mice had significantly increased urine protein, urine protein:creatinine ratio, plasma phosphorous, and plasma cystatin C, with accelerated nephropathy. Histologically, increased extracellular matrix, mesangial expansion and mesangial cell proliferation in the glomeruli were observed. Moreover, TRAIL-/-ApoE-/- kidneys displayed loss of the brush border and disorganisation of tubular epithelium, with increased fibrosis. TRAIL-deficient kidneys also had increased expression of MMPs, TIMP-1, PAI-1, IL-1β and IL-18, markers of renal injury and inflammation. Compared with ApoE-/- mice, TRAIL-/-ApoE-/- mice displayed insulin resistance and type-2 diabetic features with reduced renal insulin-receptor expression. Conclusions Here, we show that TRAIL-deficiency in ApoE-/- mice exacerbates nephropathy and insulin resistance. Understanding TRAIL signalling in kidney disease and diabetes, may therefore lead to novel strategies for the treatment of diabetic nephropathy. PMID:24667560

  6. TRAIL deficiency contributes to diabetic nephropathy in fat-fed ApoE-/- mice.

    Directory of Open Access Journals (Sweden)

    Siân P Cartland

    Full Text Available BACKGROUND: We recently demonstrated that TNF-related apoptosis-inducing ligand (TRAIL is protective of diet-induced diabetes in mice. While TRAIL has been implicated in chronic kidney disease, its role in vivo in diabetic nephropathy is not clear. The present study investigated the role of TRAIL in the pathogenesis of diabetic nephropathy using TRAIL(-/-ApoE(-/- mice. METHODS: TRAIL(-/-ApoE(-/- and ApoE(-/- mice were fed a high fat diet for 20 w. Plasma glucose and insulin levels were assessed over 0, 5, 8 and 20 w. At 20 w, markers of kidney function including creatinine, phosphate, calcium and cystatin C were measured. Changes in mRNA expression of MMPs, TIMP-1, IL-1β and IL-18 were assessed in the kidney. Functional and histological changes in kidneys were examined. Glucose and insulin tolerance tests were performed. RESULTS: TRAIL(-/-ApoE(-/- mice had significantly increased urine protein, urine protein:creatinine ratio, plasma phosphorous, and plasma cystatin C, with accelerated nephropathy. Histologically, increased extracellular matrix, mesangial expansion and mesangial cell proliferation in the glomeruli were observed. Moreover, TRAIL(-/-ApoE(-/- kidneys displayed loss of the brush border and disorganisation of tubular epithelium, with increased fibrosis. TRAIL-deficient kidneys also had increased expression of MMPs, TIMP-1, PAI-1, IL-1β and IL-18, markers of renal injury and inflammation. Compared with ApoE(-/- mice, TRAIL-/-ApoE-/- mice displayed insulin resistance and type-2 diabetic features with reduced renal insulin-receptor expression. CONCLUSIONS: Here, we show that TRAIL-deficiency in ApoE(-/- mice exacerbates nephropathy and insulin resistance. Understanding TRAIL signalling in kidney disease and diabetes, may therefore lead to novel strategies for the treatment of diabetic nephropathy.

  7. Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control.

    Science.gov (United States)

    Macedo, Célia Sperandéo; Lerco, Mauro Masson; Capelletti, Sônia Maria; Silva, Reinaldo José; Pinheiro, Daniela de Oliveira; Spadella, César Tadeu

    2007-01-01

    To determine podocyte number and GBM thickness in diabetic rats either under glycemic control or without glycemic control at 6 and 12 months after diabetes induction. 100 Wistar rats weighing 200-300g were divided into 6 groups: Normal group (N6 and N12- 25 rats); Diabetic group (D6 and D12- 25 rats), diabetic treated group ( DT 6 and DT 12- 25 rats) on insulin 1,8- 3,0 IU/Kg associated with acarbose (50 mg to 100g of food) daily mixed in chow. Alloxan was injected intravenously in a dose of 42 mg/Kg of weight. Body weight, water intake, 24-h diuresis, glycemia and glucosuria were determined before induction, 7 and 14 days after induction and monthly thereafter. Treatment started at day 14. Three groups were sacrificed at 6 months (N6,D6, DT6) and 3 groups at 12 months (N12, D12, DT12) with the renal tissue being prepared for electron microscopy. Glycemia in DT6" and in DT12 was significantly different from that in D6 and D12 rats and similar to that in N6 and N12 animals. The number of podocytes in DT6 was not different from that in N6 and D6 (median = 11); the number of podocytes in DT12 (median = 11) differed from that in D12 (median = 8), but not from that in N12 (median = 11). GBM thickness in D6 (0.18 micrometers) was lower than in D12 (0.29 micrometers); while in DT6 (0.16 micrometers) it was lower than in D6 (0.18 micrometers). In DT12 (0.26 micrometers), it was lower than in D12 (0.29 micrometers). The control of hyperglycemia prevented GBM thickening in early and late (12 mo) alloxan diabetic nephropathy and podocyte number reduction.

  8. Effect of depression on renal function as well as oxidative stress and inflammatory response in patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Xiu-Zhu Lin

    2017-05-01

    Full Text Available Objective: To study the effect of depression on renal function as well as oxidative stress and inflammatory response in patients with diabetic nephropathy. Methods: Patients with type 2 diabetes alone, patients with diabetic nephropathy and patients with diabetic nephropathy and depression treated in our hospital between May 2014 and September 2016 were selected as the research subjects and included in simple diabetes group, diabetic nephropathy group and complicated depression group, and the renal function indexes, oxidative stress indexes and inflammatory response indexes were detected. Results: Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1, and TNF-α levels in serum as well as MA and A1M levels in urine of complicated depression group and diabetic nephropathy group were significantly higher than those of simple diabetes group while serum Mn-SOD, CAT, GSH-Px and T-AOC levels were significantly lower than those of simple diabetes group; Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1, and TNF-α levels in serum as well as MA and A1M levels in urine of complicated depression group were significantly higher than those of diabetic nephropathy group while serum Mn-SOD, CAT, GSH-Px and T-AOC levels were significantly lower than those of diabetic nephropathy group. HAMD score was positively correlated with Scr, BUN, CysC, ROS, MDA, 8-OHdG, IL-6, IL-18, MCP-1, ICAM-1 and TNF-α levels in serum as well as MA and A1M levels in urine, and negatively correlated with Mn-SOD, CAT, GSH-Px and T-AOC levels in serum. Conclusion: Depression in patients with diabetic nephropathy can aggravate the renal injury and increase oxidative stress and inflammatory response.

  9. 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, Frederik; Rossing, Peter; Hovind, Peter

    2008-01-01

    OBJECTIVE: To evaluate risk factors for progression from persistent microalbuminuria to diabetic nephropathy in the Irbesartan in Patients with Type 2 diabetes and Microalbuminuria (IRMA 2) study, including biomarkers of endothelial dysfunction, chronic low-grade inflammation, growth factors and ...

  10. Predicting the Risk of Preeclampsia in Pregnant Women with Type 1 Diabetes Mellitus and Concomitant Diabetic Nephropathy: the Role of Genetic Markers

    Directory of Open Access Journals (Sweden)

    T.V. Avramenko

    2016-01-01

    Conclusions. In patients with diabetes mellitus type 1 and concomitant diabetic nephropathy without hypertension, we can recommend to study these polymorphic variants of genes to determine the risk of preeclampsia.

  11. Diabetic Nephropathy Determinant Factor in Diabetes Mellitus at RSUD Dr. M. Soewandhie Surabaya

    Directory of Open Access Journals (Sweden)

    Rahmadany Isya Putri

    2015-01-01

    Full Text Available Non communicable diseases are an important health problem related with the shift in the pattern of death cause, which is from infectious diseases to non-infectious diseases. Diabetes mellitus (DM ranked 5 of the top 10 causes of non-infectious diseases in hospitals in Indonesia. If not properly controlled, DM can lead to chronic complications such as Diabetic Nephropathy (DN. This study, conducted at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, in June-July 2014, aimed to analyze correlation between non-clinical factors according to the concept of Hendrik L. Blum, such as compliance to treatment, education level, income, and social support for the incidence of DN in DM patients. This study was an observational analytic study with case-control design. Case samples in this study were DM patients who experienced DN complications and undergoing treatment at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, by 36 respondents. Control samples in this study were diabetic patients who did not experience complications DN undergoing treatment at Internal Medicine Clinic, Outpatient Care, Dr. M. Soewandhie Hospital Surabaya, by 36 respondents. Samples were taken by using a convenience sampling method. Relation streght analysis between dependent and independent variables used Contingency Coefficient by Chi Square test with 95% Confidence Interval (α=0.05. To determine the amount of risk between dependent and independent variables, we used OR (odds ratio calculation. The results showed that non-compliance to treatment (OR=2.8 with contigency coefficient 0.243, low education (OR=1.5 with contigency coefficient 0.091, income < District Minimum Wage (OR=1.21 with contigency coefficient 0.036, and not receiving social support (OR=1.65 with contigency coefficient 0.117. In conclusion, compliance to treatment, education level, income, and social support affect the incidence of DN in DM patients

  12. The use of antihypertensive agents in prevention and treatment of diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P

    1994-01-01

    Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h), a relentless decline in glomerular filtration rate, and elevated systemic blood pressure. The prevalence of an abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in pat...

  13. 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 excretio...

  14. The effect of RAAS blockade on the progression of diabetic nephropathy

    NARCIS (Netherlands)

    Roscioni, Sara S.; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick

    The renin angiotensin aldosterone system (RAAS) has a key role in the regulation of blood pressure, sodium and water balance, and cardiovascular and renal homeostasis. In diabetic nephropathy, excessive activation of the RAAS results in progressive renal damage. RAAS blockade using

  15. Effect of the Urotensin Receptor Antagonist Palosuran in Hypertensive Patients With Type 2 Diabetic Nephropathy

    NARCIS (Netherlands)

    Vogt, Liffert; Chiurchiu, Carlos; Chadha-Boreham, Harbajan; Danaietash, Parisa; Dingemanse, Jasper; Hadjadj, Samy; Krum, Henry; Navis, Gerjan; Neuhart, Eric; Parvanova, Aneliya I.; Ruggenenti, Piero; Woittiez, Arend Jan; Zimlichman, Reuven; Remuzzi, Giuseppe; de Zeeuw, Dick

    2010-01-01

    The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion

  16. Effect of the Urotensin Receptor Antagonist Palosuran in Hypertensive Patients With Type 2 Diabetic Nephropathy

    NARCIS (Netherlands)

    Vogt, Liffert; Chiurchiu, Carlos; Chadha-Boreham, Harbajan; Danaietash, Parisa; Dingemanse, Jasper; Hadjadj, Samy; Krum, Henry; Navis, Gerjan; Neuhart, Eric; Parvanova, Aneliya I.; Ruggenenti, Piero; Woittiez, Arend Jan; Zimlichman, Reuven; Remuzzi, Giuseppe; de Zeeuw, Dick

    The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion

  17. Heparanase induces a differential loss of heparan sulphate domains in overt diabetic nephropathy.

    NARCIS (Netherlands)

    Wijnhoven, T.J.; Hoven, M.J.W. van den; Ding, H.; Kuppevelt, A.H.M.S.M. van; Vlag, J. van der; Berden, J.H.M.; Prinz, R.A.; Lewis, E.J.; Schwartz, M.; Xu, X.

    2008-01-01

    AIMS/HYPOTHESIS: Recent studies suggest that loss of heparan sulphate in the glomerular basement membrane (GBM) of the kidney with diabetic nephropathy is due to the increased production of heparanase, a heparan sulphate-degrading endoglycosidase. Our present study addresses whether heparan sulphate

  18. Text Mining of the Classical Medical Literature for Medicines That Show Potential in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2014-01-01

    Full Text Available Objectives. To apply modern text-mining methods to identify candidate herbs and formulae for the treatment of diabetic nephropathy. Methods. The method we developed includes three steps: (1 identification of candidate ancient terms; (2 systemic search and assessment of medical records written in classical Chinese; (3 preliminary evaluation of the effect and safety of candidates. Results. Ancient terms Xia Xiao, Shen Xiao, and Xiao Shen were determined as the most likely to correspond with diabetic nephropathy and used in text mining. A total of 80 Chinese formulae for treating conditions congruent with diabetic nephropathy recorded in medical books from Tang Dynasty to Qing Dynasty were collected. Sao si tang (also called Reeling Silk Decoction was chosen to show the process of preliminary evaluation of the candidates. It had promising potential for development as new agent for the treatment of diabetic nephropathy. However, further investigations about the safety to patients with renal insufficiency are still needed. Conclusions. The methods developed in this study offer a targeted approach to identifying traditional herbs and/or formulae as candidates for further investigation in the search for new drugs for modern disease. However, more effort is still required to improve our techniques, especially with regard to compound formulae.

  19. ACE Insertion/Deletion Polymorphism and Diabetic Nephropathy: Clinical Implications of Genetic Information

    Science.gov (United States)

    Ha, Sung-Kyu

    2014-01-01

    Approximately 20–40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20–80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient's ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers. PMID:25587546

  20. Risk scores for predicting outcomes in patients with type 2 diabetes and nephropathy: The RENAAL study

    NARCIS (Netherlands)

    Keane, W.F.; Zhang, Z.X.; Lyle, P.A.; Cooper, M.E.; Grunfeld, J.P.; Lash, J.P.; McGill, J.B.; Mitch, W.E.; Remuzzi, G.; Shahinfar, S.; Snapinn, S.M.; Toto, R.; Brenner, B.M.; de Zeeuw, Dick

    2006-01-01

    Diabetic nephropathy is the most important cause of ESRD. The aim of this study was to develop a risk score from risk predictors for ESRD, with and without death, in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and to compare ability of the ESRD risk

  1. Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Sato, A; Ali, S

    1999-01-01

    . A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril......OBJECTIVE: To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: M-mode echocardiography was performed in 50...... hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo...

  2. A comparison of spirapril and isradipine in patients with diabetic nephropathy and hypertension

    DEFF Research Database (Denmark)

    Nørgaard, K; Jensen, T; Christensen, P

    1993-01-01

    The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were...... studied. All had hypertension and diabetic nephropathy with a urinary albumin excretion of more than 300 mg/24 h. After a single blind placebo treatment period of 4 weeks the patients were randomly assigned to treatment with the calcium antagonist isradipine SRO 5 mg once daily or the ACE inhibitor...... spirapril 6 mg once daily for 6 months in a double-blind design. Isradipine lowered ambulatory systolic blood pressure from 152 +/- 12 to 141 +/- 11 mmHg (p blood pressure lowering effect of spirapril was similar: 156...

  3. Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Nielsen, F S; Rossing, P

    1997-01-01

    Initiation of antihypertensive treatment in hypertensive non-insulin-dependent diabetic (NIDDM) patients with diabetic nephropathy induces a faster initial (0 to 6 months) and slower subsequent (6 months-end) decline in GFR [delta GFR (ml.min-1.1.73 m-2.month-1) approximately 1.5 vs. 0.4]. Whether...... this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged antihypertensive treatment is not known. To elucidate these mechanisms we investigated 40 hypertensive NIDDM patients (age 61 +/- 7 years, mean +/- SD), known duration of diabetes 14 years (2 to 33 years......) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24...

  4. Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients

    OpenAIRE

    Arfa, Imen; Abid, Abdelmajid; Nouira, Sonia; Elloumi-Zghal, Houda; Malouche, Dhafer; Mannai, Imen; Zorgati, Mohamed Majdi; Ben Alaya, Nissaf; Rebai, Ahmed; Zouari, Béchir; Ben Ammar, Slim; Ben Rayana, Mohamed Chiheb; Hmida, Slama; Blousa-Chabchoub, Samira; Abdelhak, Sonia

    2008-01-01

    International audience; Objective. The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. Design. A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using ...

  5. Trends of diabetic nephropathy prevalence in Isfahan, Iran, during 1992-2010

    Directory of Open Access Journals (Sweden)

    Tohid Jafari-Koshki

    2015-01-01

    Full Text Available Background: Diabetes mellitus is a metabolic disorder and its subsequent complications such as retinopathy, nephropathy, ulcers, disability, and amputation increase the burden of the disease. Patient knowledge-improving programs are employed to prevent disease progression and to improve the quality of life of the patients. In this way, we need to characterize the groups of patients in urgent need for more and rich-in-content programs. In the present study, we used piecewise regression to evaluate the trends of diabetic nephropathy prevalence in patients registered in the Sedigheh-Tahereh Research Center and to identify patients who were in need of more attention. Materials and Methods: Piecewise regression, used in this study, is a statistical method to identify change points, if any, in the trends of mortality rates, prevalence of a disease, or any other trends. Available information for 1,935 patients were retrieved from the database. Joinpoint program 3.5.3 and Statistical Package for the Social Sciences (SPSS 20 was used to fit piecewise regression and obtain descriptive statistics, respectively. Results: We assessed the trend of diabetic nephropathy in different groups of diabetic patients with respect to sex, blood pressure status, education, family history of diabetes, and age. The results showed an increasing trend in females, patients without family history of diabetes, and eover th recent years. The prevalence of diabetic nephropathy in patients with academic education was high. Conclusion: The groups with high prevalence or increasing trends need more preventive intervention and detailed assessment of the present trends. Exploring high-risk groups is beneficial for better policy-making in the future. However, discovering the reasons for the increased trend of the disease is really helpful in controlling diabetes complications.

  6. Pathophysiology of obesity-related renal dysfunction contributes to diabetic nephropathy.

    Science.gov (United States)

    Bayliss, George; Weinrauch, Larry A; D'Elia, John A

    2012-08-01

    Recent studies have demonstrated the role of insulin resistance in renal injury related to obesity, with hyperfiltration leading to glomerulomegaly in a pattern similar to that found in diabetic nephropathy. Similarities in the histologic patterns of damage from obesity and diabetes point to overlapping mechanisms of injury. In this review, we will examine the hormonal mechanisms, signaling pathways and injury patterns in renal injury resulting from obesity and attempt to draw conclusions on the reasons for these similarities.

  7. Mesenchymal stem cells: a future experimental exploration for recession of diabetic nephropathy.

    Science.gov (United States)

    Hamza, Amal H; Al-Bishri, Widad M; Damiati, Laila A; Ahmed, Hanaa H

    2017-11-01

    The progresses made in stem cell therapy offer an innovative approach and exhibit great potential for the repair of damaged organs and tissues. This study was conducted with a view to find the mechanisms responsible for the effectiveness of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the suppression of diabetes and experimentally-induced diabetic nephropathy. To realize this objective, diabetic and diabetic nephropathy subject groups that underwent MSC treatment were studied through numerous biochemistry and molecular genetics analyses. The findings show that, relative to the control groups, the rats in the diabetic and diabetic nephropathy groups treated with stem cells infused with BM-MSCs showed a significant reversal in the levels of their insulin, glucose, heme-oxygenase-1 (HO-1) serum, and advanced glycation end product (AGEP). Moreover, BM-MSC therapy was also found to have a definite positive effect on the kidney functions. In addition, it also corresponded with a significant decrease in the availability of certain growth factors, namely the fibroblast growth factor (FGF), the platelet-derived growth factor (PDGF), and the transforming growth factor-β (TGF-β). BM-MSC treatment also improved the levels of expression of monocyte chemoatractant-1 (MCP-1) and interleukin-8 (IL-8) genes within kidney tissues. Lastly, the treatment recovered the organizational structure of the kidney and pancreas, a result demonstrated by a histopathological analysis. These results greatly coincide with those obtained through the biochemistry and molecular genetics analyses. Treatment using BM-MSCs is determined to be definitely effective in cases of diabetes and diabetic nephropathy.

  8. Improvement of renal oxidative stress markers after ozone administrationin diabetic nephropathy in rats

    OpenAIRE

    Morsy Mohamed D; Hassan Waleed N; Zalat Sherif I

    2010-01-01

    Abstract Background Several complications of diabetes mellitus (DM) e.g. nephropathy (DN) have been linked to oxidative stress. Ozone, by means of oxidative preconditioning, may exert its protective effects on DN. Aim The aim of the present work is to study the possible role of ozone therapy in ameliorating oxidative stress and inducing renal antioxidant defence in streptozotocin (STZ)-induced diabetic rats. Methods Six groups (n = 10) of male Sprague Dawley rats were used as follows: Group C...

  9. Lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes with diabetic nephropathy depending on the stage of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Y V Khasanova

    2012-06-01

    Full Text Available Aim: to study the role and relationship of lipid metabolism and levels of proinflammatory cytokines in patients with type 2 diabetes mellitus (DM2 with diabetic nephropathy (DN, depending on the stage of chronic kidney disease (CKD. Materials and Methods: a total of 240 patients with type 2 diabetes in the early stages of DN and CKD were studied. Results: in patients with type 2 diabetes development of DN was associated with an increased level of proinflammatory cytokines and lipid abnormalities (hypertriglyceridemia. We found a negative correlation between the level of triglycerides (TG and glomerular filtration rate (GFR (r = -0,43 and a direct correlation between the level of IL-6 and TG (r = 0,48. Conclusions: increased levels of proinflammatory cytokines and triglycerides increase the risk of development and progression of DN and CKD.

  10. Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    1996-01-01

    .0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P 300......OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a...... with and without nephropathy, respectively (P 300 U/l (at-risk level for cardiovascular...

  11. Renal protection in diabetes

    DEFF Research Database (Denmark)

    Parving, H H; Tarnow, L; Rossing, P

    1996-01-01

    BACKGROUND: The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end......-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic nephropathy is a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic...... nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. OVERVIEW: Calcium antagonists antagonize preglomerular vasoconstriction. Additional putative...

  12. Elevated MBL concentrations are not an indication of association between the MBL2 gene and type 1 diabetes or diabetic nephropathy

    DEFF Research Database (Denmark)

    Kaunisto, M.A.; Sjolind, L.; Sallinen, R.

    2009-01-01

    OBJECTIVE: Mannose-binding lectin (MBL) is an essential component of the acute-phase immune response and may thus play a role in the pathogenesis of type 1 diabetes and diabetic nephropathy. The serum concentration of MBL is mainly genetically determined, and elevated concentrations have been...... associated with both type 1 diabetes and diabetic nephropathy. Previous genetic studies have not been conclusive due to the small number of patients and polymorphisms studied. We investigated whether MBL2 polymorphisms are associated with type 1 diabetes or diabetic nephropathy and whether patients...... consisting of 1,297 patients with type 1 diabetes with or without nephropathy and 701 nondiabetic individuals. The serum concentration of MBL was available for 1,064 patients. RESULTS: We found that 19 SNPs were associated with the MBL concentration (P = 3 x 10(-81)-7 x 10(-4)). MBL concentrations were...

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

    Directory of Open Access Journals (Sweden)

    Jae Hee Ahn

    2014-04-01

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

  14. Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

    Science.gov (United States)

    Bertram, Anna; Menne, Jan

    2017-01-01

    Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40–50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD. PMID:29082239

  15. Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

    Directory of Open Access Journals (Sweden)

    Hermann Haller

    2017-01-01

    Full Text Available Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40–50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.

  16. Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate-Free Radical Scavenger and Growth Factor Inhibition.

    Science.gov (United States)

    Haller, Hermann; Ji, Linong; Stahl, Klaus; Bertram, Anna; Menne, Jan

    2017-01-01

    Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40-50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.

  17. Nephropathy in patients with recently diagonised type 2 diabetes ...

    African Journals Online (AJOL)

    Background: Albuminuria is long recognised as a sign of renal disease in diabetes. In type 1 diabetes, renal disease occurs after a longer duration of diabetic state. In type 2 diabetes, it is more variable. Objective: To determine the prevalence and any risk factors of albuminuria in shortterm (<2 yrs) type 2 diabetes. Design: ...

  18. Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Lajer, Maria Stenkil; Tarnow, Lise; Jorsal, Anders

    2008-01-01

    OBJECTIVE: To investigate whether circulating asymmetric dimethylarginine (ADMA) levels are predictive of cardiovascular events, decline in glomerular filtration rate (GFR), end-stage renal disease (ESRD), and all-cause mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We...... aged 42.7 +/- 9.7 years, duration of diabetes 27.7 +/- 8.3 years). Patients were followed for a median 11.3 years (range 0.0-12.9) with yearly measurements of GFR ((51)Cr-EDTA plasma clearance) in patients with diabetic nephropathy. Endpoints were fatal and nonfatal cardiovascular disease (CVD...... nephropathy. Furthermore, increased ADMA levels tend to contribute to increased risk of progressive diabetic kidney disease....

  19. Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Kim, Won Yong; Astrup, Anne Sofie; Stuber, Matthias

    2007-01-01

    BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic...... cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden......, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; Pcoronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P

  20. Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    1996-01-01

    ) [apo(a)] in particular to CVD in nephropathic patients with IDDM. RESEARCH DESIGN AND METHODS: We investigated 199 IDDM patients with diabetic nephropathy and 192 normoalbuminuric IDDM patients matched for sex, age, diabetes duration, and BMI. RESULTS: The prevalence of CVD was 30 and 12% in patients.......0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P 300......OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a...

  1. Oral contraceptives, angiotensin-dependent renal vasoconstriction, and risk of diabetic nephropathy

    DEFF Research Database (Denmark)

    Ahmed, Sofia B; Hovind, Peter; Parving, Hans-Henrik

    2005-01-01

    OBJECTIVE: Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic...... examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1-24). RESULTS: Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril...... = 0.72, P developed macroalbuminuria compared with 2% (2/81 [0-5.9]) of OC nonusers (P = 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression...

  2. Expression, localization, and function of the thioredoxin system in diabetic nephropathy

    DEFF Research Database (Denmark)

    Advani, Andrew; Gilbert, Richard E; Thai, Kerri

    2009-01-01

    Excessive reactive oxygen species play a key role in the pathogenesis of diabetic nephropathy, but to what extent these result from increased generation, impaired antioxidant systems, or both is incompletely understood. Here, we report the expression, localization, and activity of the antioxidant......RNA and protein localized to the renal cortex, particularly within the proximal tubules and to a lesser extent in the distal nephron. Induction of diabetes in rats increased expression of TxnIP but not thioredoxin mRNA. Kidneys from patients with diabetic nephropathy had significantly higher levels of TxnIP than...... interference RNA suggested that TxnIP mediates the glucose-induced impairment of thioredoxin activity. Knockdown of TxnIP also abrogated both glucose-induced 3H-proline incorporation (a marker of collagen production) and oxidative stress. Taken together, these findings suggest that impaired thiol reductive...

  3. Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase.

    Science.gov (United States)

    Fujii, Masakazu; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; Zheng, Jing; Kobayashi, Kunihisa; Takayanagi, Ryoichi

    2010-11-01

    We recently found a markedly lower prevalence of vascular complications, including kidney disease, in diabetic patients with Gilbert syndrome, a congenital form of hyperbilirubinemia, suggesting a beneficial effect of bilirubin (BIL) on diabetic nephropathy. To directly examine this, we determined whether hereditary hyperbilirubinemic Gunn j/j rats and biliverdin (BVD)-treated diabetic db/db mice were resistant to the development of renal disease. Both rodent models had less albuminuria and complete protection against the progression of mesangial expansion accompanied by normalization of transforming growth factor-β1 and fibronectin expression. Simultaneously, there was normalization of urinary and renal oxidative stress markers, and the expression of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits in the kidney. In cultured vascular endothelial and mesangial cells, BIL and BVD significantly inhibited NADPH-dependent superoxide production, and both high glucose- and angiotensin II-induced production of reactive oxygen species. Collectively, our findings suggest that BIL and BVD may protect against diabetic nephropathy and may lead to novel antioxidant therapies for diabetic nephropathy.

  4. Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy.

    Science.gov (United States)

    Blouza, Samira; Dakhli, Sabeur; Abid, Hafaoua; Aissaoui, Mohamed; Ardhaoui, Ilhem; Ben Abdallah, Nejib; Ben Brahim, Samir; Ben Ghorbel, Imed; Ben Salem, Nabila; Beji, Soumaya; Chamakhi, Said; Derbel, Adnene; Derouiche, Fethi; Djait, Faycal; Doghri, Taieb; Fourti, Yamina; Gharbi, Faycel; Jellouli, Kamel; Jellazi, Nabil; Kamoun, Kamel; Khedher, Adel; Letaief, Amel; Limam, Ridha; Mekaouer, Awatef; Miledi, Riadh; Nagati, Khemaies; Naouar, Meriem; Sellem, Sami; Tarzi, Hichem; Turki, Selma; Zidi, Borni; Achour, Abdellatif

    2010-01-01

    Diabetic nephropathy (DN) is the single greatest cause of end-stage renal disease (ESRD). Without specific interventions, microalbuminuria (incipient nephropathy) gradually progresses to macroalbuminuria (overt nephropathy) within 10-15 years in about 80% of type 1 and 30% of type 2 diabetic patients, and to ESRD within further 20 years in about 75% and 20%, respectively. A primary alteration in DN consists of decreased concentration of glycosaminoglycans (GAGs) in the glomerular extracellular matrix. This evidence has prompted interest in using exogenous GAGs and specifically sulodexide in DN treatment. In this uncontrolled multicenter study, diabetic patients with albumin excretion rate (AER) >or=30 mg/24 hours were treated with oral sulodexide 50 mg/day for 6 months, while receiving concomitant medication as required. Two hundred thirty-seven patients (54% males and 46% females, mean age 55 years, mean diabetes duration 11 years) were evaluated; 89% had type 2 and 11% type 1 diabetes mellitus, 67% microalbuminuria and 33% macroalbuminuria. AER was significantly and progressively reduced during sulodexide treatment (ptherapy was shown to reduce AER in patients with DN.

  5. [Hospital-primary care teamwork in nephrology: 'preventive' epidemiology of diabetic nephropathy].

    Science.gov (United States)

    Russo, D; Vico, A; Monterisi, F; Biga, M L; Falanga, R; Mancini, A; Teutonico, A; Losappio, R; Gruppo di Integrazione Territtorio-Ospedale In Nefrologia, G I T O N

    2007-01-01

    The onset of clinical proteinuria in patients with diabetic nephropathy usually marks the existence of irreversible and progressive kidney damage. Prevention of chronic renal failure ought to take place in earlier stages, mostly in the outpatient setting and in close collaboration with general practitioners (GPs). This study aims to evaluate the prevalence and the clinical stage of diabetic nephropathy and to screen for progression factors in the regional community referred to the outpatient department of the nephrology unit of the Mons. DiMiccoli Hospital in Barletta; it is intended as the first phase of a collaborative project for the prevention of diabetic nephropathy. Our team asked for the collaboration of GPs within the geographic area referring to our outpatient department. This led to the institution of a working group aimed at interrelating primary with hospital care in the setting of nephrology. The clinical data of diabetic patients as well as their codified personal data were classified by GPs and subsequently processed by the nephrology team. The glomerular filtration rate was estimated by means of the abbreviated MDRD study equation. Finally, the cumulative prevalence of known risk factors for diabetic nephropathy progression was assessed in a subgroup of 201 diabetic patients. Within the whole group of screened subjects from the regional community (21,314), the prevalence of diabetes was 3.54%, and the rates of personal and clinical features did not show any substantial differences from the ones recorded in Italy as a whole. In the subgroup of 201 diabetic patients, the cumulative frequency of progression factors for diabetic nephropathy showed a relevant percentage of subjects with clinical and laboratory features deviating from the targets proposed by current guidelines, thus justifying the adoption of specific prevention plans. This study shows the feasibility and the advantages of setting up a stable collaboration between hospital and primary

  6. "Vitamin D supplementation and bone health in adults with diabetic nephropathy: the protocol for a randomized controlled trial"

    National Research Council Canada - National Science Library

    Mager, Diana R; Jackson, Stephanie T; Hoffmann, Michelle R; Jindal, Kailash; Senior, Peter A

    2014-01-01

    ... health is a major challenge. It is unknown what level of vitamin D supplementation will ameliorate or improve suboptimal vitamin D status in patients with diabetic nephropathy or contribute to improved bone health, particularly...

  7. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

    Directory of Open Access Journals (Sweden)

    Jingsong Shi

    2016-01-01

    Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

  8. Risk Factors Accompanied with Nephropathy in Patients with Type II Diabetes; Test of the Biopsychosocial Model

    Directory of Open Access Journals (Sweden)

    I. Rahimian Boogar

    2012-07-01

    Full Text Available Introduction & Objective: The study of biopsychosocial factors influencing nephropathy as a most serious complication of type II diabetes is important. This study aimed to investigate risk factors accompanied with nephropathy in patients with type II diabetes based on the biopsychosocial model. Materials & Methods: In a cross-sectional descriptive study, 295 patients with type II diabetes were selected by convenience sampling in Tehran Shariati hospital outpatient clinics. The data were collected by demographical information questionnaire along with disease characteristics and depression anxiety stress scales (dass, quality of life scale (who- qol- bref, diabetes self-management scale (dsms, and diabetes knowledge scale (dks, then analyzed by chi-square, independent t-test and logistic regression with pasw software. Results: Hypertension (OR=3.841 & P0.05.Conclusion: It is important to pay attention to hypertension, glycated hemoglobin, body mass index, diabetes self-management, depression, quality of life, and diabetes knowledge for therapeutic intervention programming and diabetes complications control protocols for diabetic patients.(Sci J Hamadan Univ Med Sci 2012;19(2:44-53

  9. Increased oxidative stress in diabetic nephropathy and its relationship with soluble Klotho levels

    Science.gov (United States)

    Inci, A; Olmaz, R; Sarı, F; Coban, M; Ellidag, HY; Sarıkaya, M

    2016-01-01

    Background: In the present study, we aimed to assess the relationship between the levels of soluble Klotho (s-Klotho) and oxidative stress markers in diabetic nephropathy patients with different stages of chronic kidney disease (CKD) and albuminuria levels. Methods: We enrolled 109 patients with type 2 diabetes (mean age, 61.63 ± 9.77 years) and 32 healthy controls (mean age, 49.53 ± 7.32 years) between January and June 2014.  Patients were classified into three groups based on their urinary albumin/creatinine ratio (UACR). Blood samples were collected to measure the levels of s-Klotho, serum creatinine, calcium, phosphorus, 25-hydroxyvitamin D3, and parathyroid hormone (PTH). We used the total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and ischemia-modified albumin ratio (IMAR) values to measure the oxidative status. Moreover, the oxidative stress index (OSI) was estimated as the percentage ratio of TOS/TAS values. Results: The TOS, TAS, and OSI values were significantly greater in the diabetic nephropathy patients compared to controls (p IMAR (p =0.002) values significantly differed between the groups. The s-Klotho levels also significantly differed (p =0.031) between the groups. These s-Klotho levels exhibited a significant positive correlation with TOS (r =0.186, p =0.034) and OSI (r =0.207 p =0.018), but showed no correlation with the estimated glomerular filtration rate; UACR; HbA1c, calcium, phosphorus, and PTH levels; and TAS, IMA, and IMAR values. Conclusion: Oxidative stress is greater in patients with diabetic nephropathy, and the TOS was positively correlated with s-Klotho levels in diabetic patients. The therapeutic reduction of oxidative stress in patients with diabetic nephropathy could improve the renal and cardiovascular outcomes. Hippokratia 2016, 20(3): 198-203. PMID:29097885

  10. Therapeutic approaches to slowing the progression of diabetic nephropathy – is less best?

    Directory of Open Access Journals (Sweden)

    Eva Vivian

    2013-03-01

    Full Text Available Objective: Angiotensin II receptor blockers (ARBs and angiotensin-converting enzyme (ACE inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin–angiotensin–aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI, to monotherapy.Design: Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012 and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs.Setting: Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review.Participants: Adult (≥18 years patients with diabetic nephropathy.Measurements: Serum creatinine level was used to estimate glomerular filtration rate (GFR. GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine was defined as macroalbuminuria.Results: ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk

  11. Therapeutic approaches to slowing the progression of diabetic nephropathy - is less best?

    Science.gov (United States)

    Vivian, Eva; Mannebach, Chelsea

    2013-03-27

    Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin-angiotensin-aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy. Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012) and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs. Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Adult (≥18 years) patients with diabetic nephropathy. Serum creatinine level was used to estimate glomerular filtration rate (GFR). GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine) was defined as macroalbuminuria. ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk of hyperkalemia or acute kidney injury. Both ACE inhibitors and ARBs remain

  12. Therapeutic approaches to slowing the progression of diabetic nephropathy – is less best?

    Science.gov (United States)

    Vivian, Eva; Mannebach, Chelsea

    2013-01-01

    Objective: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin–angiotensin–aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy. Design: Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012) and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs. Setting: Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Participants: Adult (≥18 years) patients with diabetic nephropathy. Measurements: Serum creatinine level was used to estimate glomerular filtration rate (GFR). GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine) was defined as macroalbuminuria. Results: ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk of

  13. Free Triiodothyronine Levels Are Associated with Diabetic Nephropathy in Euthyroid Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jingcheng Wu

    2015-01-01

    Full Text Available Objective. To investigate the association of thyroid function and diabetic nephropathy (DN in euthyroid patients with type 2 diabetes. Methods. A total of 421 patients were included in this cross-sectional study. The following parameters were assessed: anthropometric measurements, fast plasma glucose, serum creatinine, lipid profile, HbA1c, free triiodothyronine (FT3, free thyroxine, thyroid-stimulating hormone levels, and urinary albumin-to-creatinine ratio (UACR. Patients with UACR of ≥30 mg/g were defined as those suffering from DN. Results. Of the 421 patients, 203 (48.2% suffered from DN, and no difference was found between males and females. The patients with DN yielded significantly lower FT3 levels than those without DN (P<0.01. The prevalence of DN showed a significantly decreasing trend across the three tertiles based on FT3 levels (59.6%, 46.4%, and 38.6%, P<0.01. After adjustment for gender and age, FT3 levels were found to correlate positively with estimated glomerular filtration rate (P=0.03 and negatively with UACR (P<0.01. Multiple linear regression analysis showed that FT3 level was independently associated with UACR (β=-0.18, t=-3.70, and P<0.01. Conclusion. Serum FT3 levels are inversely associated with DN in euthyroid patients with type 2 diabetes, independent of traditional risk factors.

  14. Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus.

    Science.gov (United States)

    Tsutsui, Hideyo; Nomura, Kyoko; Ohkubo, Takayoshi; Ozaki, Nobuaki; Kusunoki, Masataka; Ishiguro, Tetsuya; Oshida, Yoshiharu

    2016-04-01

    We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM. A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including "Body functions", "Body structures", "Activities and participation", and "Environmental factors". The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes. The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy.

  15. DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy

    Science.gov (United States)

    Kaida, Yusuke; Fukami, Kei; Matsui, Takanori; Higashimoto, Yuichiro; Nishino, Yuri; Obara, Nana; Nakayama, Yosuke; Ando, Ryotaro; Toyonaga, Maki; Ueda, Seiji; Takeuchi, Masayoshi; Inoue, Hiroyoshi; Okuda, Seiya

    2013-01-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2′-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy. PMID:23630304

  16. Albuminuria in nondiabetic relatives of IDDM patients with and without diabetic nephropathy.

    Science.gov (United States)

    Fagerudd, J A; Pettersson-Fernholm, K J; Riska, M K; Grönhagen-Riska, C; Groop, P H

    2000-09-01

    In non-insulin-dependent diabetes mellitus (NIDDM), there is a clustering of an elevated urinary albumin excretion rate (U-AER) in nondiabetic relatives of albuminuric patients. Whether this is also the case in insulin-dependent diabetes mellitus (IDDM) is unknown. Overnight U-AER was measured in 186 nondiabetic first-degree relatives of 80 IDDM patients with diabetic nephropathy (U-AER > 200 microg/min or 300 mg/24 hours; DN+) and in 52 relatives of 25 IDDM patients without nephropathy (U-AER therapy, and smoking habits. No difference was found in overnight U-AER between relatives of patients with DN+ and DN- [median (range), 3.4 (0.1 to 372) vs. 4.0 (0.2 to 62) microg/min, respectively, P = NS]. The proportion of relatives with a U-AER = 10 microg/min was 12% in DN+ compared with 8% in DN- (P = NS). Among relatives of DN+, those with antihypertensive treatment (AHT+) had higher U-AER compared with those without [AHT+ vs. AHT-, 5.0 (0.5 to 372) vs. 3.4 (0.1 to 26.5) microg/min, P AER in nondiabetic relatives of patients with nephropathy. This is different from what has been reported in NIDDM, and suggests heterogeneity in the genesis of albuminuria in diabetes.

  17. Effects of Apolipoprotein E Isoforms in Diabetic Nephropathy of Chinese Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    YongWei Jiang

    2017-01-01

    Full Text Available Diabetic nephropathy (DN is one of the major chronic complications of diabetes. Genetic polymorphism of Apolipoprotein E (ApoE has been proposed to participating in DN. The purpose of the study was to evaluate the relationship between ApoE genetic polymorphism and the presence of DN in Chinese type 2 diabetic patients. We studied 845 diabetic patients who were divided into DN group (n=429 and control group (n=416. ApoE genotype was determined by ApoE genotyping chip and the plasmatic biochemical characterization was performed on all subjects. There were differences (P<0.001 in HbA1c, creatinine, and urinary albumin between the two groups. The ApoE ε2 allelic frequency was 7.69% in DN group versus 3.49% in control group (OR = 2.22, 95% CI = 1.41–3.47, and P<0.05, as expected, ApoE E2/E2 and E2/E3 genotype frequency were higher in DN group (13.75% versus 6.49%, P<0.05. The ApoE ε4 allelic frequency was 7.93% in DN group versus 11.54% in control group (OR = 0.70, 95% CI = 0.50–0.97, and P<0.05, and DN group presented a lower frequency of ApoE E3/E4 and E4/E4 genotype frequency (14.91% versus 19.96%, P<0.05. These results suggest ApoE ε2 allele may be a risk factor; however ApoE ε4 allele may play a protective role of DN in Chinese type 2 diabetic patients.

  18. The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2014-05-01

    Full Text Available Diabetic nephropathy (DN has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS in streptozotocin (STZ-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.

  19. Pro12Ala Polymorphism in the PPARG Gene Contributes to the Development of Diabetic Nephropathy in Chinese Type 2 Diabetic Patients

    Science.gov (United States)

    Liu, Limei; Zheng, Taishan; Wang, Feng; Wang, Niansong; Song, Yanyan; Li, Ming; Li, Lifang; Jiang, Jiamei; Zhao, Weijing

    2010-01-01

    OBJECTIVE Oxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator–activated receptor γ heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among patients, 532 had diabetic nephropathy with microalbuminuria (n = 245) or overt albuminuria (n = 287), and 228 did not show either of these symptoms but had had diabetes for ≥10 years and were not undergoing antihypertension treatment. RESULTS After adjustment for confounders, the Pro/Pro genotype was significantly associated with diabetic nephropathy (odds ratio 2.30 [95% CI 1.18–4.45], P = 0.014); smoking was also an independent risk factor for diabetic nephropathy (1.99 [1.08–3.68], P = 0.029). In addition, we identified possible synergistic effects; i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (1.78–11.48, P = 0.002) of diabetic nephropathy than the low-risk group (nonsmokers with the Pro/Ala genotype) in a multiple logistic regression analysis controlled for the confounders. CONCLUSIONS Our results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy. PMID:19837787

  20. MicroRNA biomarkers in clinical renal disease: from diabetic nephropathy renal transplantation and beyond.

    Science.gov (United States)

    Nassirpour, Rounak; Raj, Dominic; Townsend, Raymond; Argyropoulos, Christos

    2016-12-01

    Chronic Kidney Disease (CKD) is a common health problem affecting 1 in 12 Americans. It is associated with elevated risks of mortality, cardiovascular disease, and high costs for the treatment of renal failure with dialysis or transplantation. Advances in CKD care are impeded by the lack of biomarkers for early diagnosis, assessment of the extent of tissue injury, estimation of disease progression, and evaluation of response to therapy. Such biomarkers should improve the performance of existing measures of renal functional impairment (estimated glomerular filtration rate, eGFR) or kidney damage (proteinuria). MicroRNAs (miRNAs) a class of small, non-coding RNAs that act as post-transcriptional repressors are gaining momentum as biomarkers in a number of disease areas. In this review, we examine the potential utility of miRNAs as promising biomarkers for renal disease. We explore the performance of miRNAs as biomarkers in two clinically important forms of CKD, diabetes and the nephropathy developing in kidney transplant recipients. Finally, we highlight the pitfalls and opportunities of miRNAs and provide a broad perspective for the future clinical development of miRNAs as biomarkers in CKD beyond the current gold standards of eGFR and albuminuria. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Association of levels of mannose-binding lectin and the MBL2 gene with type 2 diabetes and diabetic nephropathy.

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    Nana Zhang

    Full Text Available OBJECTIVE: To investigate the association of Mannose-binding lectin (MBL and the MBL2 gene with type 2 diabetes and diabetic nephropathy and the influence of MBL2 polymorphisms on serum MBL levels. METHODS: The study population included 675 type 2 diabetic patients with or without nephropathy and 855 normoglycemic controls. The single nucleotide polymorphisms (SNPs of rs1800450, rs1800451, and rs11003125 of the MBL2 gene were determined by the Multiplex Snapshot method. Serum MBL levels were measured by enzyme-linked immune sorbent assay. RESULTS: Rs1800450 and rs11003125 SNPs demonstrated strong linkage disequilibrium in the study population (r(2 = 0.97. The haplotypes constructed from the G allele of rs1800450 and the C allele of rs11003125 increased the risk for type 2 diabetes (OR = 1.2, 95% CI = 1.1-1.4, P = 0.01. For rs1800450, GG and GA genotypes were associated with type 2 diabetes (P = 0.02, 0.01, respectively. For rs11003125, the GC genotype frequency was significantly different between patients and controls (18.1% vs. 24.9%, P = 0.001. Analyses of genotypes and allele frequency distributions among patients with normal UAE, microalbuminuria, and macroalbuminuria showed that there was no obvious evidence of association between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels. CONCLUSIONS: The rs1800450 and rs11003125 SNPs of the MBL2 gene have strong linkage disequilibrium and are associated with type 2 diabetes in the North Chinese Han population. No association was observed between the MBL2 gene and diabetic nephropathy. Subjects with the GG genotype of rs1800450 and the CC genotype of rs11003125 had much higher serum MBL levels. An association between elevated serum MBL and diabetic nephropathy was also observed.

  2. The Association Between Smoking Tobacco After a Diagnosis of Diabetes and the Prevalence of Diabetic Nephropathy in the Korean Male Population.

    Science.gov (United States)

    Yeom, Hyungseon; Lee, Jung Hyun; Kim, Hyeon Chang; Suh, Il

    2016-03-01

    Smoking is known to be associated with nephropathy in patients with diabetes. The distinct effects of smoking before and after diabetes has been diagnosed, however, are not well characterized. We evaluated the association of cigarette smoking before and after a diagnosis of diabetes with the presence of diabetic nephropathy. We analyzed data from the 2011-2013 editions of the Korea National Health and Nutrition Examination Survey. A total of 629 male patients diagnosed with diabetes were classified as non-smokers (90 patients), former smokers (225 patients), or continuing smokers (314 patients). A "former smoker" was a patient who smoked only before receiving his diagnosis of diabetes. A "continuing smoker" was a patient who smoked at any time after his diabetes had been diagnosed. Diabetic nephropathy was defined as the presence of albuminuria (spot urine albumin/creatinine ratio ≥30 mg/g) or low estimated glomerular filtration rate (smoked. Compared to non-smokers, continuing smokers had significantly higher odds ratio ([OR], 2.17; 95% confidence interval [CI], 1.23 to 3.83) of suffering from diabetic nephropathy. The corresponding OR (95% CI) for former smokers was 1.26 (0.70 to 2.29). Smoking after diagnosis of diabetes is significantly associated with the presence of diabetic nephropathy in the Korean male population.

  3. Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    1996-01-01

    .0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P 300......OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a...

  4. Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism.

    Science.gov (United States)

    Liang, Guang; Song, Lintao; Chen, Zilu; Qian, Yuanyuan; Xie, Junjun; Zhao, Longwei; Lin, Qian; Zhu, Guanghui; Tan, Yi; Li, Xiaokun; Mohammadi, Moosa; Huang, Zhifeng

    2018-01-01

    Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic intraperitoneal administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models. Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast growth factor 1 was able to correct the elevated blood glucose levels in type 2 but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of fibroblast growth factor 1 was independent of its glucose-lowering activity. The mechanistic study demonstrated that fibroblast growth factor 1-mediated inhibition of the renal inflammation in vivo was accompanied by attenuation of the nuclear factor κB and c-Jun N-terminal kinase signaling pathways, further validated in vitro using cultured glomerular mesangial cells and podocytes. Thus, fibroblast growth factor 1 holds great promise for developing new treatments for diabetic nephropathy through countering inflammatory signaling cascades in injured renal tissue. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Role of Obesity in the Progression of Diabetic Nephropathy in Patients with Diabetes Mellitus (Literature Review

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    S.U. Аhmedova

    2016-11-01

    Full Text Available The prevalence of obesity has risen proportionally to epidemic and continues to be a major health problem worldwide. The high prevalence of obesity is closely associated with the increased incidence of chronic diseases, such as diabetes mellitus, hypertension and cardiovascular diseases. Obesity, as well as diabetes mellitus and hypertension, is the main cause of chronic kidney disease and end-stage renal disease. The presence of at least one of these risk factors increases the overall risk of developing the disease. The pathophysiology of diabetic nephropathy and renal diseases associated with obesity are nearly identical. In addition, they lead to the development of successive chan­ges, from an increase in glomerular filtration rate and intraglomerular capillary pressure to glomerular hypertrophy and microalbuminuria. Increased systolic blood pressure further aggravates the process and causes the disease progression to proteinuria, nodular glomerulosclerosis, tubulointerstitial renal disease and reduced glomerular filtration rate leading to the development of end-stage renal failure. White adipose tissue — not only a fat storage organ, but also is now recognized as a dynamic tissue involved in the production of adipokines, such as leptin, adiponectin, etc. The balance between these adipokines allows adipose tissue to regulate appetite, food intake, glucose clearance, ener­gy expenditure. Imbalance in obesity stimulates an inflammatory environment and leads to insulin resistance. Kidney disease related to obesity is associated with disorders of renal hemodynamics, dysfunction of endothelium and podocytes, damage to the glomerular basement membrane, mesangial expansion, tubular atrophy, interstitial fibrosis and progressive decline in renal function (increased albuminuria and decreased glomerular filtration rate leading to the development of end-stage renal disease. Nevertheless, there is no clear understanding of the mechanisms, by which

  6. Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic Nephropathy.

    Science.gov (United States)

    Marquardt, Andi; Al-Dabet, Moh'd Mohanad; Ghosh, Sanchita; Kohli, Shrey; Manoharan, Jayakumar; ElWakiel, Ahmed; Gadi, Ihsan; Bock, Fabian; Nazir, Sumra; Wang, Hongjie; Lindquist, Jonathan A; Nawroth, Peter Paul; Madhusudhan, Thati; Mertens, Peter R; Shahzad, Khurrum; Isermann, Berend

    2017-11-01

    Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells. Indeed, TUDCA induced expression of FXR-dependent genes (SOCS3 and DDAH1) in tubular cells but not in other renal cells. In vivo, TUDCA reduced glomerular and tubular injury in db/db and diabetic endothelial nitric oxide synthase-deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA. Notably, these in vivo approaches abolished tubular but not glomerular protection by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more efficiently than did either treatment alone. Although both therapies reduced glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions that specifically protect the tubular compartment in dNP, such as FXR agonism, may provide renoprotective effects on top of those achieved by inhibiting angiotensin-converting enzyme. Copyright © 2017 by the American Society of Nephrology.

  7. Comparison of the effects of levocetirizine and losartan on diabetic nephropathy and vascular dysfunction in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Anbar, Hanan S; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M

    2016-06-05

    This work was designed to investigate the effects of levocetirizine, a histamine H1 receptor antagonist, on diabetes-induced nephropathy and vascular disorder, in comparison to an angiotensin II receptor antagonist, losartan. Diabetes was induced in male Sprague Dawley rats by a single intraperitoneal injection of streptozotocin (50mg/kg). Diabetic rats were divided into three groups; diabetic, diabetic-levocetirizine (0.5mg/kg/day) and diabetic-losartan (25mg/kg/day). Treatments were started two weeks following diabetes induction and continued for additional eight weeks. At the end of the experiment, urine was collected and serum was separated for biochemical measurements. Tissue homogenates of kidney and aorta were prepared for measuring oxidative stress, nitric oxide (NO), transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Moreover, histological analyses were conducted and aortic vascular reactivity was investigated. Levocetirizine improved renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney to body weight ratio, serum albumin, urinary proteins and creatinine clearance). Moreover, levocetirizine attenuated the elevated renal levels of TNF-α and TGF-β1, ameliorated renal oxidative stress and restored NO bioavailability in diabetic kidney. These effects were comparable to or surpassed those produced by losartan. Moreover, levocetirizine, similar to losartan, reduced the enhanced responsiveness of diabetic aorta to phenylephrine. Histological evaluation of renal and aortic tissues further confirmed the beneficial effects of levocetirizine on diabetic nephropathy and revealed a greater attenuation of diabetes-induced vascular hypertrophy by levocetirizine than by losartan. In conclusion, levocetirizine may offer comparable renoprotective effect to, and possibly superior vasculoprotective effects than, losartan in streptozotocin-diabetic rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Reliability of peripheral arterial tonometry in patients with heart failure, diabetic nephropathy and arterial hypertension.

    Science.gov (United States)

    Weisrock, Fabian; Fritschka, Max; Beckmann, Sebastian; Litmeier, Simon; Wagner, Josephine; Tahirovic, Elvis; Radenovic, Sara; Zelenak, Christine; Hashemi, Djawid; Busjahn, Andreas; Krahn, Thomas; Pieske, Burkert; Dinh, Wilfried; Düngen, Hans-Dirk

    2017-08-01

    Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.

  9. Soy milk consumption and blood pressure among type 2 diabetic patients with nephropathy.

    Science.gov (United States)

    Miraghajani, Maryam Sadat; Najafabadi, Mojgan Mortazavi; Surkan, Pamela J; Esmaillzadeh, Ahmad; Mirlohi, Maryam; Azadbakht, Leila

    2013-07-01

    The purpose of this study was to determine the effects of soy milk consumption cardiovascular risk and biomarkers of renal function in type 2 diabetic patients with nephropathy. This randomized, crossover, controlled clinical trial was conducted in 29 type 2 diabetic patients with nephropathy. Participants were randomly assigned to consume a diet containing soy milk, or a diet containing cow's milk, each for 4 weeks. There was a 2-week washout between the two intervention periods. Anthropometric and biochemical measurements were performed according to standard protocols. The mean age and body mass index of patients were 51 ± 10 years and 28 ± 4 kg/m(2), respectively. Consumption of soy milk resulted in a significant reduction in systolic blood pressure compared with consumption of cow's milk (percent change: -4.50 vs. 5.89%; P = .03). Serum triglyceride levels decreased significantly after soy milk consumption (percent change: -15.22 vs. 2.37%; P = .02). After adjustment for carbohydrate intake, the effect of soy milk on triglyceride level was not significant. There were no significant differences between soy milk and cow's milk consumption in terms of their effect on cardiovascular risks and markers of kidney function. Soy milk consumption was associated with better blood pressure control among diabetic patients with nephropathy. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.

  10. Early pre-eclampsia unmasks underlying IgA nephropathy

    OpenAIRE

    Mona Singh; Akhenaton Pappoe; Burl R Don

    2010-01-01

    Mona Singh, Akhenaton Pappoe, Burl R DonDivision of Nephrology, University of California Davis Medical Center, Sacramento, CA, USAAbstract: Pre-eclampsia is the most ominous complication of pregnancy, and primary glomerular diseases can mimic pre-eclampsia in presentation. A patient presented at 21 weeks gestation with signs and symptoms of both pre-eclampsia and primary glomerular nephropathy. A critical clinical decision whether to continue or terminate the pregnancy was dependent on result...

  11. Advanced glycation end products assessed by skin autofluorescence in type 1 diabetics are associated with nephropathy, but not retinopathy.

    Science.gov (United States)

    Chabroux, S; Canouï-Poitrine, F; Reffet, S; Mills-Joncour, G; Morelon, E; Colin, C; Thivolet, C

    2010-04-01

    Advanced glycation end products (AGEs) are thought to play a central role in the pathogenesis of diabetes complications. For this reason, a non-invasive tool using skin autofluorescence (AF) quantification that correlates with levels of tissue AGEs has been developed. The present study aimed to assess whether or not skin AF is associated with microvascular complications in patients with type 1 diabetes (T1D). All consecutive patients with T1D (n=133) had three AF measures taken on the forearm, using illumination with a fluorescent tube, all on the same day after breakfast or lunch. Potential associations between skin AF levels and microvascular complications, age, diabetes duration and health status were then assessed using a multivariate linear-regression model. On age-adjusted analyses, diabetes duration, retinopathy, nephropathy and neuropathy were significantly associated with skin AF levels (all P<0.001). AF levels increased significantly with severity in both retinopathy and nephropathy (P<0.001). After adjusting for age, diabetes duration, HbA(1c), smoking, retinopathy, nephropathy and neuropathy, the association of AF levels remained significant with nephropathy and neuropathy, but not with retinopathy and diabetes duration. This study suggests an independent association between skin AF levels and diabetic nephropathy and neuropathy, but not retinopathy, in T1D patients. Prospective studies are needed to confirm the ability of skin AF levels to predict microangiopathy. (c) 2010 Elsevier Masson SAS. All rights reserved.

  12. High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

    Science.gov (United States)

    Dower, Ken; Zhao, Shanrong; Schlerman, Franklin J; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P; Wang, Ju; Nie, Qing; Karsdal, Morten A; Genovese, Federica; Boucher, Germaine; Brown, Thomas P; Zhang, Baohong; Homer, Bruce L; Martinez, Robert V

    2017-01-01

    ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

  13. Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han's patients with type 1 diabetes mellitus.

    Science.gov (United States)

    Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping

    2017-03-31

    Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P regression analysis showed bilirubin concentrations were independently associated with 24 h urinary microalbumin. In logistic regression analysis, bilirubin concentrations were significantly inversely associated with nephropathy. In addition, in stratified analysis, from the first to the fourth quartile group, increased bilirubin concentrations were associated with decreased prevalence of DN from 21.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

  14. The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes.

    Science.gov (United States)

    Ahola, Aila J; Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Dahlström, Emma; Groop, Per-Henrik

    2017-05-01

    Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  15. The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

    Directory of Open Access Journals (Sweden)

    Isabele Beserra Santos Gomes

    2015-09-01

    Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

  16. Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

    National Research Council Canada - National Science Library

    Romero, Montserrat; Ortega, Arantxa; Olea, Nuria; Arenas, María Isabel; Izquierdo, Adriana; Bover, Jordi; Esbrit, Pedro; Bosch, Ricardo J

    2013-01-01

    ... to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria...

  17. The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes

    DEFF Research Database (Denmark)

    Möllsten, A; Jorsal, Anders; Lajer, Maria Stenkil

    2009-01-01

    AIMS/HYPOTHESIS: Hyperglycaemia increases oxidative stress and may thereby increase the risk of diabetic complications, including diabetic nephropathy. Cells are protected from oxidative damage by, for example, the manganese superoxide dismutase enzyme (MnSOD), but the functional polymorphism V16A...... affects the localisation of MnSOD and therefore its ability to scavenge superoxide radicals. In a Danish cohort of type 1 diabetes patients, we sought to confirm previous findings of association between the V allele and the risk of diabetic nephropathy and to investigate the influence of this polymorphism...... on the development of cardiovascular disease. METHODS: Type 1 diabetes patients attending the Steno Diabetes Center, Gentofte, Denmark, between 1993 and 2001 were enrolled in this study. A total of 441 cases with diabetic nephropathy (albumin excretion > or =300 mg/24 h) and 314 controls with persistent...

  18. The Diagnosis of Minimal Change Disease in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    M. Barry Stokes

    2005-01-01

    Full Text Available Proteinuria is common in diabetic patients and usually reflects the presence of diabetic glomerulosclerosis. This paper reviews the differential diagnosis of proteinuria in diabetic patients and discusses the role of renal biopsy examination in identification and management of minimal change disease in this cohort. Identification of nondiabetic glomerular disease requires careful correlation of clinical history and renal biopsy findings and may have important implications for prognosis and therapy.

  19. Association of aldose reductase gene Z+2 polymorphism with reduced susceptibility to diabetic nephropathy in Caucasian Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Lajer, Mathilde; Tarnow, L; Fleckner, Jan

    2004-01-01

    AIMS: The Z-2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether this polymorph......AIMS: The Z-2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether...... of the ALR2 promoter polymorphism is associated with a reduced susceptibility to diabetic nephropathy in Danish Type 1 diabetic patients, suggesting a minor role for the polyol pathway in the pathogenesis of diabetic kidney disease. No association of the ALR2 polymorphism with diabetic retinopathy was found....

  20. Influence of peritoneal transport characteristics on nutritional status and clinical outcome in Chinese diabetic nephropathy patients on peritoneal dialysis.

    Science.gov (United States)

    Guan, Ji-Chao; Bian, Wei; Zhang, Xiao-Hui; Shou, Zhang-Fei; Chen, Jiang-Hua

    2015-04-05

    High peritoneal transport status was previously thought to be a poor prognostic factor in peritoneal dialysis (PD) patients. However, its effect on diabetic nephropathy PD patients is unclear in consideration of the adverse impact of diabetes itself. The purpose of this study was to investigate the influence of peritoneal transport characteristics on nutritional status and clinical outcome in diabetic nephropathy patients on PD. One hundred and two diabetic nephropathy patients on PD were enrolled in this observational cohort study. According to the initial peritoneal equilibration test result, patients were divided into two groups: Higher transport group (HT, including high and high average transport) and lower transport group (LT, including low and low-average transport). Demographic characteristics, biochemical data, dialysis adequacy, and nutritional status were evaluated. Clinical outcomes were compared. Risk factors for death-censored technique failure and mortality were analyzed. Compared with LT group (n = 37), serum albumin was significantly lower and the incidence of malnutrition by subjective global assessment was significantly higher in HT group (n = 65) (P renal function (RRF) were independent predictors of death-censored technique failure when adjusted for serum albumin and total weekly urea clearance (Kt/V). Independent predictors of mortality were advanced age, anemia, hypoalbuminemia, and lower RRF, but not higher peritoneal transport status. Higher peritoneal transport status has an adverse influence on nutrition for diabetic nephropathy patients on PD. Higher peritoneal transport status is a significant independent risk factor for death-censored technique failure, but not for mortality in diabetic nephropathy patients on PD.

  1. Nephropathy and Neuropathy in Diabetic Patients with Chronic ...

    African Journals Online (AJOL)

    Introduction: Several reports described an association between type 2 diabetes mellitus (DM) and chronic hepatitis C virus (HCV) infection. Chronic HCV infection is prevalent in Egypt. The present work aimed to evaluate the prevalence of proteinuria and neuropathy among diabetic patients with and without chronic HCV ...

  2. The role of human serum carnosinase-1 in diabetic nephropathy

    NARCIS (Netherlands)

    Zhang, Shiqi

    2016-01-01

    Diabetische nephropaty (DN), een nierziekte die ontstaat ten gevolge van diabetes, is de meest voorkomende oorzaak voor nierfalen. Uit verschillende genetische studies is gebleken dat niet alle patienten met diabetes even gevoelig zijn voor het ontstaan van DN, maar dat dit ten dele wordt bepaald

  3. Eucommia bark (Du-Zhong improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats

    Directory of Open Access Journals (Sweden)

    Niu HS

    2016-03-01

    Full Text Available Ho-Shan Niu,1 I-Min Liu,2 Chiang-Shan Niu,1 Po-Ming Ku,3,4 Chao-Tien Hsu,5 Juei-Tang Cheng4,6 1Department of Nursing, Tzu Chi University of Science and Technology, Hualien City, 2Department of Pharmacy & Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County, 3Department of Cardiology, 4Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, 5Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung City, 6Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan Background: Eucommia bark, Eucommia ulmoides Oliver barks (Du-Zhong in Mandarin, is an herb used for renal dysfunction in Chinese traditional medicine. In an attempt to develop this herb as a treatment for diabetic nephropathy (DN, we investigated the effects of Du-Zhong on renal dysfunction in type 1-like diabetic rats. Methods: Streptozotocin (STZ was used to induce type 1-like diabetes in rats (STZ-diabetic rats. In addition to hyperglycemia, STZ-diabetic rats showed significant nephropathy, including higher plasma levels of blood urea nitrogen, creatinine, and renal fibrosis. Western blot analysis of renal cortical tissue was applied to characterize the changes in potential signals related to nephropathy. Results: Oral administration of Du-Zhong (1 g/kg/day to STZ-diabetic rats for 20 days not only decreased the plasma levels of blood urea nitrogen and creatinine but also improved renal fibrosis, whereas the plasma glucose level was not changed. The higher expressions of protein levels of transforming growth factor-beta (TGF-β and connective tissue growth factor in diabetic rats were markedly attenuated by Du-Zhong. The increased phosphorylation of Smad2/3 in STZ-diabetic rats was also reduced by Du-Zhong. However, Du-Zhong cannot reverse the hyperglycemia-induced overproduction of signal transducers and activators of transcription 3 in the diabetic kidney

  4. Fufang Xue Shuan Tong capsules inhibit renal oxidative stress markers and indices of nephropathy in diabetic rats.

    Science.gov (United States)

    Fang, Donghong; Wan, Xuesi; Deng, Wanping; Guan, Hongyu; Ke, Weijian; Xiao, Haipeng; Li, Yanbing

    2012-11-01

    Fufang Xue Shuan Tong (FXST) capsules, a traditional Chinese medicine, have been used to treat diabetic nephropathy for many years. FXST has been shown to attenuate elevated levels of oxidative stress in the retina of diabetic rats. However, whether FXST protects kidneys through the same mechanism(s) remains unclear. In this study, diabetes was induced in rats by administration of a high-fat diet and low-dose streptozotocin. Rats were administered low (450 mg/kg/day), middle (900 mg/kg/day) or high (1800 mg/kg/day) doses of FXST orally for 3 months. Another group was administered 50 mg/kg/day orally for the same period. The results indicated that all doses of FXST reduced urinary protein excretion and creatinine clearance and ameliorated the diabetic nephropathy-related mesangial matrix expansion. However, only middle and high doses of FXST prevented glomerular hypertrophy in diabetic rats, and the high dose showed the greatest inhibitory effect with regard to mesangial matrix expansion. Furthermore, superoxide dismutase activities were significantly elevated, whereas malondialdehyde levels were significantly reduced in the renal cortex following FXST treatment. The kidney-protective role of FXST is not inferior to that of captopril, one of the most commonly used drugs for the treatment of diabetic nephropathy. In conclusion, FXST retards the progression of diabetic nephropathy, while high-dose FXST shows the most prominent effect in counteracting the pathological changes of diabetic nephropathy. The renoprotective action of FXST is induced by the reduction of oxidative stress in diabetic nephropathy.

  5. Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Montilla, Pedro; Barcos, Montserrat; Munoz, Maria C; Bujalance, Inmaculada; Munoz-Castaneda, Juan R; Tunez, Isaac

    2005-09-30

    We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.

  6. Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats.

    Science.gov (United States)

    Hofni, Amal; El-Moselhy, Mohamed A; Taye, Ashraf; Khalifa, Mohamed M

    2014-12-05

    Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Science.gov (United States)

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  8. Enhanced expression of two discrete isoforms of matrix metalloproteinase-2 in experimental and human diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    Full Text Available We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2 in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2 and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2 generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms.We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. The streptozotocin (STZ murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study.Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold. Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively.The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal

  9. Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy.

    Science.gov (United States)

    Nørgaard, Sisse A; Sand, Fredrik W; Sørensen, Dorte B; Abelson, Klas Sp; Søndergaard, Henrik

    2018-01-01

    The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.

  10. Assessment of glomerular filtration rate in diabetic nephropathy using the plasma clearance of 51Cr-EDTA

    DEFF Research Database (Denmark)

    Hansen, H P; Rossing, P; Mathiesen, E R

    1998-01-01

    Plasma clearance of 51Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total 51Cr...... and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq 51Cr...

  11. Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis

    NARCIS (Netherlands)

    Mohamed, Riyaz; Jayakumar, Calpurnia; Chen, Feng; Fulton, David; Stepp, David; Gansevoort, Ron T.; Ramesh, Ganesan

    Diabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially

  12. ACE variants interact with the RAS pathway to confer risk and protection against type 2 diabetic nephropathy

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Ahuja, Monica; Rai, Taranjit Singh

    2009-01-01

    Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Among candidate genes examined for susceptibility to diabetic nephropathy, angiotensin-converting enzyme (ACE) gene has been found to be associated with pathogenesis and progr...

  13. Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1 gene with diabetic nephropathy in north Indians

    Directory of Open Access Journals (Sweden)

    Ashok K Yadav

    2016-01-01

    Interpretation & conclusions: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

  14. Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in Westernized South Asian people

    NARCIS (Netherlands)

    van den Berg, Else; Hospers, Frederique; Navis, Gerjan; Engberink, Marielle F.; Brink, Elizabeth J.; Geleijnse, Johanna M.; van Baak, Marleen A.; Gans, Rijk O. B.; Bakker, Stephan J. L.

    2011-01-01

    Diabetic nephropathy is now the most common cause of end-stage renal failure in many countries of the world. Despite increasing implementation of preventive treatment, the chance that an individual diabetic patient will reach end-stage renal failure has been increasing rather than decreasing during

  15. Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in westernized South Asian people

    NARCIS (Netherlands)

    Berg, E. van den; Hospers, F.A.P.; Navis, G.; Engberink, M.F.; Brink, E.J.; Geleijnse, J.M.; Baak, M.A. van; Gans, R.O.B.; Bakker, S.J.L.

    2011-01-01

    Diabetic nephropathy is now the most common cause of end-stage renal failure in many countries of the world. Despite increasing implementation of preventive treatment, the chance that an individual diabetic patient will reach end-stage renal failure has been increasing rather than decreasing during

  16. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes.

    Science.gov (United States)

    De Nicola, Luca; Gabbai, Francis B; Liberti, Maria Elena; Sagliocca, Adelia; Conte, Giuseppe; Minutolo, Roberto

    2014-07-01

    Optimal prevention and treatment of chronic kidney disease in diabetes requires implementing therapies that specifically interfere with the pathogenesis of diabetic nephropathy. In this regard, significant attention has been given to alterations of the proximal tubule and resulting changes in glomerular filtration rate. At the onset of diabetes mellitus, hyperglycemia causes increases in proximal tubular reabsorption secondary to induction of tubular growth with associated increases in sodium/glucose cotransport. The increase in proximal reabsorption leads to a decrease in solute load to the macula densa, deactivation of the tubuloglomerular feedback, and increases in glomerular filtration rate. Because glomerular hyperfiltration currently is recognized as a risk factor for progression of kidney disease in diabetic patients, limiting proximal tubular reabsorption constitutes a potential target to reduce hyperfiltration. The recent introduction of sodium/glucose cotransporter 2 (SGLT2) inhibitors opens new therapeutic perspectives for this high-risk patient population. Experimental studies have shown that these new agents attenuate the progressive nature of diabetic nephropathy by blood glucose-dependent and -independent mechanisms. SGLT2 inhibition may prevent glomerular hyperfiltration independent of the effect of lowering blood glucose levels while limiting kidney growth, inflammation, and albuminuria through reductions in blood glucose levels. Clinical data for the potential role of the proximal tubule in the pathophysiology of diabetic nephropathy and the nephroprotective effects of SGLT2 inhibitors currently are limited compared to the more extensive experimental literature. We review the evidence supporting this working hypothesis by integrating the experimental findings with the available clinical data. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  17. Endothelial progenitor cells in long-standing asymptomatic type 1 diabetic patients with or without diabetic nephropathy

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Jacobsen, Peter Karl; Lajer, Maria

    2011-01-01

    A decrease in the number and dysfunction of endothelial progenitor cells (EPC) may increase the risk for progression of cardiovascular disease (CVD) in type 1 diabetic patients with diabetic nephropathy (DN). Our aim was to evaluate EPC numbers in asymptomatic CVD type 1 diabetic patients...... with or without DN and to study the effect of CVD and medication on EPC numbers. Methods: We examined EPC numbers in 37 type 1 diabetic patients with DN and 35 type 1 diabetic patients with long-standing normoalbuminuria. Patients were without symptoms of CVD and the prevalence of CVD was previously shown...... patients with DN had EPC numbers similar to normoalbuminuric patients, which was related to aggressive CVD intervention therapy. This may have contributed to the low prevalence of CVD....

  18. Expression of toll-like receptor 2 in glomerular endothelial cells and promotion of diabetic nephropathy by Porphyromonas gingivalis lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    Yoshihiko Sawa

    Full Text Available The toll-like receptor (TLR has been suggested as a candidate cause for diabetic nephropathy. Recently, we have reported the TLR4 expression in diabetic mouse glomerular endothelium. The study here investigates the effects of the periodontal pathogen Porphyromonas gingivalis lipopolysaccharide (LPS which is a ligand for TLR2 and TLR4 in diabetic nephropathy. In laser-scanning microscopy of glomeruli of streptozotocin- and a high fat diet feed-induced type I and type II diabetic mice, TLR2 localized on the glomerular endothelium and proximal tubule epithelium. The TLR2 mRNA was detected in diabetic mouse glomeruli by in situ hybridization and in real-time PCR of the renal cortex, the TLR2 mRNA amounts were larger in diabetic mice than in non-diabetic mice. All diabetic mice subjected to repeated LPS administrations died within the survival period of all of the diabetic mice not administered LPS and of all of the non-diabetic LPS-administered mice. The LPS administration promoted the production of urinary protein, the accumulation of type I collagen in the glomeruli, and the increases in IL-6, TNF-α, and TGF-β in the renal cortex of the glomeruli of the diabetic mice. It is thought that blood TLR ligands like Porphyromonas gingivalis LPS induce the glomerular endothelium to produce cytokines which aid glomerulosclerosis. Periodontitis may promote diabetic nephropathy.

  19. Calcium antagonists and the diabetic hypertensive patient

    DEFF Research Database (Denmark)

    Parving, H H; Rossing, P

    1993-01-01

    reduces albuminuria, delays the progression of nephropathy, and postpones renal insufficiency in diabetic nephropathy. Calcium antagonists and angiotensin converting enzyme inhibitors induce an acute increase in the glomerular filtration rate, renal plasma flow, and renal sodium excretion...... nephropathy alone and is rapidly rising. Increased arterial blood pressure is an early and common finding in incipient and overt diabetic nephropathy. Fluid and sodium retention with normal concentrations of active renin, angiotensin I and II, and aldosterone has been demonstrated in diabetic renal disease...

  20. Novel hydrogen sulfide-releasing compound, S-propargyl-cysteine, prevents STZ-induced diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Xin [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Li, Xinghui [Departments of Physiology and Pathophysiology, Shanghai College of Medicine, Fudan University, Shanghai (China); Ma, Fenfen; Luo, Shanshan [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Ge, Ruowen [Departmentof Biological Sciences, National University of Singapore (Singapore); Zhu, Yizhun, E-mail: zhuyz@fudan.edu.cn [Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai (China); Departmentof Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore (Singapore)

    2016-05-13

    In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H{sub 2}S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover, SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy. - Highlights: • We synthesized a novel hydrogen sulfide-releasing compound, S-propargyl-cysteine (SPRC). • SPRC was preliminarily demonstrated to prevent STZ-induced diabetic nephropathy (DN). • SPRC may exert potential therapeutic candidate to suppress DN.

  1. BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial.

    Science.gov (United States)

    Leehey, David J; Zhang, Jane H; Emanuele, Nicholas V; Whaley-Connell, Adam; Palevsky, Paul M; Reilly, Robert F; Guarino, Peter; Fried, Linda F

    2015-12-07

    Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease. BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on-treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured. The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P150 mmHg (P=0.02), with a significantly higher hazard ratio for 140-149 versus 120-129 mmHg (1.51 [1.06, 2.15]; P=0.02). There was also a significant association of mean diastolic BP with the hazard of developing the primary end point (P<0.01), with a significantly higher hazard ratio when mean diastolic BP was 80-89 versus 70-79 mmHg (1.54 [1.05, 2.25]; P=0.03); there was also a strong trend when mean diastolic BP was <60 mmHg. Associations between BP and both renal end point and rate of eGFR decline were similar to those with the primary end point. No association of BP with mortality was observed, possibly because of the limited number of mortality events. In patients with proteinuric diabetic kidney disease, mean systolic BP ≥ 140 mmHg and mean diastolic BP ≥ 80 mmHg were associated with worse renal outcomes. Copyright © 2015 by the American Society of Nephrology.

  2. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a 4......-year randomized, intervention study evaluating low-protein diet in T1D patients with diabetic nephropathy, 78 patients were studied with yearly measurements of u-NGAL (ELISA, BioPorto). Outcome: Decline in glomerular filtration rate (GFR) ((51)Cr-EDTA), and end-stage renal disease (ESRD) or death...

  3. Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy : a systematic review

    NARCIS (Netherlands)

    Huang, Yunyu; Zhou, Qiyun; Haaijer-Ruskamp, Flora M.; Postma, Maarten J.

    2014-01-01

    Background: Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. Methods: A systematic

  4. 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.

    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 for multiple...

  5. The Selected Traditional Chinese Medicinal Formulas for Treating Diabetic Nephropathy: Perspective of Modern Science

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2013-07-01

    Full Text Available With the increasing patients and limited therapeutic options, diabetic nephropathy (DN is a long-term complication of diabetic mellitus. The precise mechanism of DN is not yet fully understood and the effective blockade of the progression of nephropathy remains a therapeutic challenge. Application of traditional Chinese medicine (TCM for diabetes and its related complications has received increasing attention due to its wide availability, low side effects, and proven therapeutic mechanisms and benefits. In the current review, we mainly focus on the recent laboratory studies of the TCM formulas including Wu-Ling-San (Poria Five Powder; 五苓散 Wǔ Líng Sǎn, Danggui-Buxue-Tang (Tangkuei and Astragalus Decoction; 當歸補血湯 Dāng Guī Bǔ Xuè Tang, and Danggui-Shaoyao-San (Tangkuei and Paeonia Formula; 當歸芍藥散 Dāng Guī Sháo Yào Sǎn, conducted by the Committee on Chinese Medicine and Pharmacy at the Department of Health of Taiwan Government, in the amelioration of DN. These selected TCM formulas have anti-diabetic properties, with antihyperglycemic activity accompanied by amelioration of advanced glycation end product–mediated renal damage in streptozotocin-induced diabetic rats. However, the renoprotective effects of the selected TCM formulas did not correlate with suppressing renal renin–angiotensin system hyperactivity in diabetic rats. These TCM formulas also have the capacity to ameliorate the defective antioxidative defense system, leading to modulation of the oxidative stress, thereby resulting in downregulation of nuclear factor-κB as well as transforming growth factor-β1 and, consequently, attenuation of extracellular matrix components such as fibronectin or type IV collagen expression in diabetic renal cortex tissue. More detailed mechanistic researches and long-term clinical evaluations, as well as evaluation of safety of the selected TCM formulas are needed for their future applications in DN therapy.

  6. Plasma proteins production and excretion in diabetic nephropathy in ...

    African Journals Online (AJOL)

    Knowledge of these potential relationships is important to understand both the mechanistic associations between albuminuria and hyperfibrinogenaemia. Therefore, this study was designed to measure fibrinogen and albumin concentrations in patients with type II diabetes who had normal or increased urinary albumin ...

  7. Transplantation for diabetic nephropathy at Groote Schuur Hospital

    African Journals Online (AJOL)

    survival rates in diabetics were 87% and 62% respectively. Vascular disease was a IIlajor prob- lem. Six patients developed limb gangrene, and symptomatic coronary and cerebrovascular disease developed in 2 patients. Infections were common and included wound sepsis, cellulitis, candidiasis and urinary tract infections.

  8. Transplantation for diabetic nephropathy at Groote Schuur Hospital ...

    African Journals Online (AJOL)

    Vascular disease was a major problem. Six patients developed limb gangrene, and symptomatic coronary and cerebrovascular disease developed in 2 patients. Infections were common and included wound sepsis, cellulitis, candidiasis and urinary tract infections. Diabetes was poorly controlled after transplantation in 5 ...

  9. Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic

    Directory of Open Access Journals (Sweden)

    Al-Wakeel Jamal

    2009-01-01

    Full Text Available To evaluate the diabetic complications and fate of diabetic nephropathy in Saudi population, we studied 184 diabetic nephropathy (DN patients who were referred to nephrology clinic of King Khalid University Hospital, Riyadh, Saudi Arabia from January 2003-June 2006. The patients had mean age of 61.9 ± 13.1 years, included 128 (69.6% males, and were followed up for a mean period of 10.2 ± 1.5 years. The mean duration of diabetes mellitus (DM was 19.5 ± 5.8 years, and duration of nephropathy was 7.7 ± 3.3 years. Family history of DN was documented in 52 (28.2% patients. At initial visit, the mean systolic blood pressure was 164 ± 14.5 mmHg, the mean diastolic blood pressure was 97.9 ± 10.4 mmHg. Thirty-seven (20% patients had normal BMI, 88 (48% were overweight, while 55 (30% were obese. Mean creatinine clearance was 51.7 ± 26.3 mL/min, 24 hrs urinary proteins 1.99 ± 2.48 gm/day, HbA1C 9.2 ± 1.8 %, triglyceride 2.1 ± 1.3 mmol/L, and cholesterol 5.17 ± 1.54 mmol/L. Diabetic complications included angiography proven coronary artery disease in 106 (57.6 % patients, stroke in 21 (11.4%, myocardial infarction (MI in 27(14.6%, angina in 87 (47.2 %, retinopathy in 82 (44.5%, Blindness in 3 (1.6%, peripheral vascular disease in 121 (65.7%, Neuropathy in 123 (66.8%, hypertension in178 (96.7%, diabetic foot in 25 (13.5%, Amputation in 10 (5.4%, and end-stage renal disease in 70 (38%. Total of 13 (7.05% patients died in the hospital. Thirty-seven percent of patients developed > 6 concomitant complications. 28% developed 5, 17% developed 4, and the rest developed < 3. DN was relatively refractory to therapy and progressive; 123 (66.8% patients doubled their serum creatinine in 3.59 ± 2.88 years, 32 (17.3% maintained stable renal function, 136 (73.6 % deteriorated, and 12 (6.52% improved. we conclude that the prevalence of diabetic complications is high among Saudi patients, and many had multiple complications. Baseline creatinine clearance and

  10. Quantitative iTRAQ-Based Proteomic Identification of Candidate Biomarkers for Diabetic Nephropathy in Plasma of Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Thingholm, Tine Engberg; Larsen, Martin R

    2010-01-01

    immunoassay confirmed the overall protein expression patterns observed by the iTRAQ analysis. CONCLUSION: The candidate biomarkers discovered in this cross-sectional cohort may turn out to be progression biomarkers and might have several clinical applications in the treatment and monitoring of diabetic......INTRODUCTION: As part of a clinical proteomics programme focused on diabetes and its complications, it was our goal to investigate the proteome of plasma in order to find improved candidate biomarkers to predict diabetic nephropathy. METHODS: Proteins derived from plasma from a cross......-sectional cohort of 123 type 1 diabetic patients previously diagnosed as normoalbuminuric, microalbuminuric or macroalbuminuric were enriched with hexapeptide library beads and subsequently pooled within three groups. Proteins from the three groups were compared by online liquid chromatography and tandem mass...

  11. The pattern-recognition molecule mannan-binding lectin (MBL) in the pathophysiology of diabetic nephropathy

    DEFF Research Database (Denmark)

    Axelgaard, Esben; Thiel, Steffen; Hansen, Troels Krarup

    The pattern-recognition molecule mannan-binding lectin (MBL) in the pathophysiology of diabetic nephropathy Esben Axelgaard*; Steffen Thiel*; Jakob Appel Østergaard† and Troels Krarup Hansen† *Department of Biomedicine, Aarhus University, Wilhelm Meyer´s Allé 4, 8000 Aarhus C, Denmark. †Department...... of Clinical Medicine, Aarhus University and The Danish Diabetes Academy, Nørrebrogade 44, build. 3, 8000 Aarhus C, Denmark The complement system is part of the innate immune system and is an important part of the first line of defence against pathogens. Mannan-binding lectin (MBL) is one of the pattern...... to carbohydrates of both specific type and density, which thus provides sufficient binding avidity. The character of MBL binding-sites on host cells remain unknown, but it is speculated that altered protein glycation in diabetes permits MBL binding. Based on new studies using MBL/double knockout C57bl/6j mice, we...

  12. Predicting diabetic nephropathy in insulin-dependent patients

    DEFF Research Database (Denmark)

    Mogensen, C E; Christensen, Cramer

    1984-01-01

    We studied whether microalbuminuria (urinary albumin excretion rates of 15 to 150 micrograms per minute) would predict the development of increased proteinuria in Type I diabetes. We also studied the influence of glomerular filtration rate, renal blood flow, and blood pressure on the later...... development of proteinuria. Forty-four patients who had had Type I diabetes for at least seven years and who had albumin excretion rates below 150 micrograms per minute were studied from 1969 to 1976, and 43 were restudied in 1983. Of the 14 who initially had albumin excretion rates at or above 15 micrograms...... per minute, 12 had clinically detectable proteinuria (over 500 mg of protein per 24 hours) or an albumin excretion rate above 150 micrograms per minute at the later examination. Of the 29 who initially had albumin excretion rates below 15 micrograms per minute, none had clinically detectable...

  13. Strategies to reverse endothelial dysfunction in diabetic nephropathy

    OpenAIRE

    Badal, Shawn S.; Danesh, Farhad R.

    2012-01-01

    Endothelial dysfunction underlies the basic pathophysiology of microvascular complications of diabetes. Endothelial dysfunction is associated with impaired nitric oxide (NO) availability. Since NO production is tightly regulated by endothelial nitric oxide synthase (eNOS), several therapeutic strategies have been investigated and proposed to improve eNOS bioavailability in the vasculature. The findings of Cheng et al. suggest that increased availability of eNOS may be an effective strategy in...

  14. Correlation between Retinopathy, Nephropathy and Peripheral ...

    African Journals Online (AJOL)

    Diabetes Mellitus is a worldwide common metabolic disorder. Increasing prevalence of diabetes, lack of proper education about the nature and course of the disease and necessary control are the main factors for an early onset of micro vascular complications. Objective: To correlate between retinopathy, nephropathy and ...

  15. Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1.

    Science.gov (United States)

    Zhang, Xiaoqian

    2013-01-01

    The aim of this study was to investigate whether calcium dobesilate (calcium dihydroxy-2,5-benzenesulfonate) may be used to treat diabetic nephropathy. A total of 121 patients with type 2 diabetic nephropathy received calcium dobesilate (500 mg, 3 times a day) for 3 months. The levels of glycated hemoglobin, fasting serum C peptide, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, γ-glutamyl transferase, urea nitrogen, creatinine, hematocrit, plasma viscosity, whole blood reduced viscosity, high, medium and low shear rate whole blood viscosity, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and endothelin were determined. The urinary albumin excretion rate (UAER) was also determined once a month during the study. The UAER and medium and low shear rate whole blood viscosity were significantly lower in the treated patients. The rate of microalbuminuria normalization was 90%. During the treatment, the UAERs decreased. The results revealed that calcium dobesilate has therapeutic effects on type 2 diabetes patients with microalbuminuria. In addition, the benefit was positively correlated with the calcium dobesilate treatment time. The therapeutic effect may be due to decreases in the levels of PAI-1.

  16. Why Is Diabetes Mellitus a Risk Factor for Contrast-Induced Nephropathy?

    Directory of Open Access Journals (Sweden)

    Samuel N. Heyman

    2013-01-01

    Full Text Available Contrast-induced nephropathy (CIN remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media. The pathophysiology of this vulnerability is complex and involves various mechanisms, including a priori enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. The regulation of vascular tone and peritubular blood flow may also be altered, particularly due to defective nitrovasodilation, enhanced endothelin production, and a particular hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro- and macrovascular diseases and chronic tubulointerstitial changes further compromise regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these susceptible patients.

  17. 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.

  18. Polyphenols of Hibiscus sabdariffa improved diabetic nephropathy via attenuating renal epithelial mesenchymal transition.

    Science.gov (United States)

    Yang, Yi-Sun; Wang, Chau-Jong; Huang, Chien-Ning; Chen, Mu-Lin; Chen, Ming-Jinn; Peng, Chiung-Huei

    2013-08-07

    We previously reported that Hibiscus sabdariffa polyphenol extracts (HPE) are beneficial for diabetic nephropathy. Since an epithelial to mesenchymal transition (EMT) is critical in renal fibrosis, the present study aimed to investigate whether HPE could prevent EMT of tubular cells. Treatment of HPE reduced angiotensin II receptors (AT)-1 and transforming growth factor β1 (TGF-β1) evoked by high glucose and recovered the increased vimentin and decreased E-cadherin. HPE decreased fibronectin, thus avoiding EMT and accompanying fibrosis. AT-1 was upstream to TGF-β1, while there were recruitment signals between AT-1 and TGF-β1. Scan electron microscopy (SEM) and immunohistochemistry (IHC) revealed that the interacting filaments of tubular cells disappeared when treated with high glucose, and type IV collagen of tubulointerstitial decreased in diabetic kidneys. Treatment of HPE recovered morphological changes of cell junction and basement membrane. We suggest that HPE has the potential to be an adjuvant for diabetic nephropathy by regulating AT-1/TGF-β1 and EMT.

  19. [Preliminary analysis of the relationship between peripheral arterial disease and other atherosclerosis markers and diabetic nephropathy].

    Science.gov (United States)

    Rioja, José; Moreno, Tamara; Coca, Inmaculada; Jiménez-Villodres, Manuel; Rodríguez-Morata, Alejandro; Valdivielso, Pedro

    2014-01-01

    To determine lipid serum levels, lipoproteins and other markers related to nephropathy and peripheral arterial disease (PAD) in a type 2 diabetes population stratified according to their level of renal dysfunction. A cross-sectional study was conducted on 72 type 2 diabetic patients followed-up in outpatient clinics. Patients were divided into 4 groups according to their estimated glomerular filtration rate (eGFR, mL/min) and albumin/creatinine ratio (ACR, mg/g) (eGFR > 60 and ACR 60 and ACR > 30 [n = 12], eGFR30-60 [n = 23] and eGFR renal and hematology parameters were measured. Finally, a multivariate Wald stepwise logistic regression statistic analysis was performed to determine variables independently associated with the presence of renal dysfunction. The univariate statistical analysis showed that the higher renal dysfunction, the higher the prevalence of hypertension, smoking habit and triglycerides levels, and the lower hemoglobin levels (P renal dysfunction (eGFR < 60 mL/min.). The further inclusion of the presence of PAD in the statistical model did not modify those associations. The results confirm the relationship between triglycerides levels and diabetic nephropathy, independently of the presence of PAD. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  20. Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice.

    Directory of Open Access Journals (Sweden)

    Sung-Hsun Yu

    Full Text Available Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-β1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN.

  1. Sensitivity of Total Protein Creatinine Ratio in Urine for Diagnosis Diabetic Nephropathy

    OpenAIRE

    Fatrinawati, .; Windarwati, .; Sianipar, Osman

    2017-01-01

    ABSTRACTDiabetic nephropathy is one of diabetic complication characterized by proteinuria and impaired renal function. Confirmation of diagnosis based either on urine value of albumin excretion rate (AER) 30-300 mg/24 hours or albumin creatinine ratio (ACR) 30-300 mg/g or total protein creatinine ratio (TPCR) 150-500 mg/g. It is reported that TPCR measurement is more acceptable since it is convenient, fast and does not require special preparation. The aim of this study is to investigate the a...

  2. Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Rossing, P; Tarnow, L

    1996-01-01

    The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood......-118); P albuminuria [microgram/min; median (range)] was observed; [Day: group I, 1467 (235-3933); group II, 695 (170-6719); group III, 875 (228-3173). Night: group I, 1079 (279-4665); group II, 572 (113-3807); group...... III, 659 (81-2493)]. A significant correlation between MABP and albuminuria was demonstrated during day- (rho = 0.50, P

  3. Circadian rhythm of arterial blood pressure and albuminuria in diabetic nephropathy

    DEFF Research Database (Denmark)

    Hansen, H P; Rossing, P; Tarnow, L

    1996-01-01

    The aim of our study was to evaluate the diurnal relationship between arterial blood pressure and albuminuria, and some potential mechanisms responsible for impaired nocturnal blood pressure reduction (non-dippers, groups I and II) in diabetic nephropathy (DN). Twenty-four-hour ambulatory blood...... was about the same in the three groups. Our study indicated an association between blood pressure and albuminuria, but the mechanisms involved in the reduction of albuminuria from day to night was not unraveled. A relative lack of sympathetic withdrawal during sleep seems to be an important feature...

  4. Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients.

    Science.gov (United States)

    Arfa, Imen; Abid, Abdelmajid; Nouira, Sonia; Elloumi-Zghal, Houda; Malouche, Dhafer; Mannai, Imen; Zorgati, Mohamed Majdi; Ben Alaya, Nissaf; Rebai, Ahmed; Zouari, Béchir; Ben Ammar, Slim; Ben Rayana, Mohamed Chiheb; Hmida, Slama; Blousa-Chabchoub, Samira; Abdelhak, Sonia

    2008-03-01

    The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals. The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without nephropathy (DD: 44%; ID: 46%; II: 10% vs. DD: 41%; ID: 47 %; II: 12%, respectively). There was also no significant statistical difference between the genotype distribution and allele frequencies of the (I/D) polymorphism in all type 2 diabetic subjects compared to non-diabetic controls with normal fasting blood glucose (DD: 43%; ID: 46%; II: 11% vs. DD: 37%; ID: 48%; II: 15%, respectively). In the present preliminary study, the (I/D) polymorphism within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population.

  5. Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy

    DEFF Research Database (Denmark)

    Clausen, P; Jacobsen, P; Rossing, K

    2000-01-01

    AIMS: Elevated urinary albumin excretion is associated with macrovascular atherosclerotic complications in Type 1 diabetes mellitus. Adhesion molecules mediate leucocyte adhesion to the endothelium early in the atherosclerotic process. The present study tests the hypothesis that microalbuminuria...... disease in diabetic patients with renal complications. METHODS: Soluble adhesion molecule concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in healthy controls (n = 16) and in 59 Type 1 diabetic patients: group 1-patients with normoalbuminuria (n = 16); group 2-patients...... and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess cardiovascular...

  6. Uric acid as a mediator of diabetic nephropathy

    DEFF Research Database (Denmark)

    Jalal, Diana I; Maahs, David M; Hovind, Peter

    2011-01-01

    evidence has emerged in the past decade to suggest uric acid is an inflammatory factor and may play a role in endothelial dysfunction. This has lead our group and others to explore the role of uric acid in the onset and progression of DN. In this review, we highlight some of the animal and human studies...... that implicate uric acid in DN. Based on the evidence we review, we conclude the need for properly planned randomized controlled studies to decrease uric acid levels and assess the impact of such therapy on diabetic kidney disease....

  7. Aldosterone synthase (CYP11B2) -344T/C polymorphism is not associated with the initiation and progression of diabetic nephropathy in Caucasian Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Lajer, Mathilde; Schjoedt, K J; Jacobsen, P

    2006-01-01

    AIMS: Aldosterone is one of the main effectors of the renin-angiotensin-aldosterone system regulating blood pressure. Previous studies have shown that the aldosterone synthase promoter polymorphism -344T/C influences aldosterone levels and is associated with hypertension, a risk factor...... for the initiation and progression of diabetic nephropathy. Therefore, we investigated whether the -344T/C polymorphism is associated with the development and progression of diabetic nephropathy in Type 1 diabetes mellitus. METHODS: The -344T/C polymorphism was determined using standard PCR techniques in 422 Type 1...

  8. Renin-angiotensin-aldosterone-blockade is associated with decreased use of antidepressant therapy in patients with type 1 diabetes and diabetic nephropathy.

    Science.gov (United States)

    Ahola, Aila J; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik

    2014-08-01

    Hypertension and depression are frequent comorbidities of diabetes. Studies suggest that antihypertensive medication affecting the renin-angiotensin-aldosterone system (RAAS) might also relieve depression. Whether this is also seen in patients with type 1 diabetes is not known. We therefore studied whether use of RAAS-modifying medication is associated with reduced antidepressant use in type 1 diabetes. In all, 1,705 participants in the FinnDiane Study were included (57 % men, mean age 46 ± 11 years). Data on medications were obtained from the Drug Prescription Register. Based on their albumin excretion rate (AER), the patients were classified as having normal AER, microalbuminuria, or macroalbuminuria. Diabetic nephropathy was defined as macroalbuminuria or end-stage renal disease (dialysis or renal transplant). A total of 8.4 and 10.9 % of patients with and without RAAS-modifying medication, respectively, had antidepressant medication purchases (NS). In logistic regression analysis, after adjusting for potential confounding factors, use of RAAS-modifying medication was not associated with antidepressant purchases. However, when patients with and without diabetic nephropathy were analyzed separately, RAAS-modifying medication was associated with lower frequency of antidepressant purchases among patients with established diabetic nephropathy. In conclusion, use of RAAS-modifying medication may improve mood in patients with type 1 diabetes and established diabetic nephropathy.

  9. Endothelin-1 Gene Polymorphisms rs5370, rs1476046, and rs3087459 are not Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Šeruga Maja

    2017-09-01

    Full Text Available Background: Diabetic nephropathy (DN is a major microvascular complication of type 2 diabetes mellitus (T2DM. Several lines of evidence implicate the endothelin (ET system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1 gene affect susceptibility to DN in Caucasians with T2DM.

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

    Science.gov (United States)

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

    2015-09-04

    Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb. In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention. Copyright © 2015 by the American Society of Nephrology.

  11. Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study

    DEFF Research Database (Denmark)

    Hovind, Peter; Rossing, Peter; Tarnow, Lise

    2009-01-01

    OBJECTIVE: Experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension and kidney disease. Whether uric acid has a causal role in the development of diabetic nephropathy is not known. The objective of the present study is to evaluate uric acid...... as a predictor of persistent micro- and macroalbuminuria. RESEARCH DESIGN AND METHODS: This prospective observational follow-up study consisted of an inception cohort of 277 patients followed from onset of type 1 diabetes. Of these, 270 patients had blood samples taken at baseline. In seven cases, uric acid...... could not be determined; therefore, 263 patients (156 men) were available for analysis. Uric acid was measured 3 years after onset of diabetes and before any patient developed microalbuminuria. RESULTS: During a median follow-up of 18.1 years (range 1.0-21.8), 23 of 263 patients developed persistent...

  12. Effects of Ayurvedic treatment on 100 patients of chronic renal failure (other than diabetic nephropathy).

    Science.gov (United States)

    Patel, Manish V; Gupta, S N; Patel, Nimesh G

    2011-10-01

    Chronic renal failure (CRF) refers to an irreversible deterioration in renal function, which develops over a period of years. This initially manifests only as a biochemical abnormality. CRF is considered when glomerular filtration rate (GFR) falls below 30 ml/min. The conventional approach of management includes dialysis and renal transplantation, which are not affordable by Indian population mainly due to economic reasons. Therefore, exploration of a safe and alternative therapy is needed, which proves to be helpful in reducing the requirement of dialysis and in postponing the renal transplantation. A clinical study of 100 patients of CRF was conducted at OPD and IPD of PD Patel Ayurved Hospital, Nadiad. They were given Niruha basti of Punarnavadi kvatha daily with oral medicaments including Goksuradi guggulu, Rasayana churna, and Varunadi kvatha for 1 month period. The patients of CRF, having diabetic nephropathy as a cause, were excluded since a separate study for diabetic nephropathy is being conducted. Results were analyzed statistically using the "t" test. The symptoms and signs, serum creatinine, blood urea, urine albumin level were reduced, which were found to be statistically highly significant on "t" test.

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

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    Itay Israel Shemesh

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Despite optimal treatment, including renin-angiotensin system (RAS) inhibitors, patients with type 2 diabetic nephropathy have high cardiorenal morbidity and mortality related to residual albuminuria. We evaluated whether or not atrasentan, a selective endothelin A receptor antagonist, further...... reduces albuminuria when administered concomitantly with maximum tolerated labeled doses of RAS inhibitors. We enrolled 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300-3500 mg/g, and eGFRs of 30-75 ml/min per 1.73 m(2) in two identically designed, parallel, multinational, double......, respectively) and reduced albuminuria≥30% in 51% and 55% of participants, respectively. eGFR and office BP measurements did not change, whereas 24-hour systolic and diastolic BP, LDL cholesterol, and triglyceride levels decreased significantly in both treatment groups. Use of atrasentan was associated...

  15. 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...... albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used...... data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes...

  16. Proteomics and diabetic nephropathy: what have we learned from a decade of clinical proteomics studies?

    Science.gov (United States)

    Papale, Massimo; Di Paolo, Salvatore; Vocino, Grazia; Rocchetti, Maria Teresa; Gesualdo, Loreto

    2014-06-01

    Diabetic nephropathy (DN) has become the most frequent cause of chronic kidney disease worldwide due to the constant increase of the incidence of type 2 diabetes mellitus in developed and developing countries. The understanding of the pathophysiological mechanisms of human diseases through a large-scale characterization of the protein content of a biological sample is the key feature of the proteomics approach to the study of human disease. We discuss the main results of over 10 years of tissue and urine proteomics studies applied to DN in order to understand how far we have come and how far we still have to go before obtaining a full comprehension of the molecular mechanisms involved in the pathogenesis of DN and identifying reliable biomarkers for accurate management of patients.

  17. Birth weight--a risk factor for progression in diabetic nephropathy?

    DEFF Research Database (Denmark)

    Jacobsen, P; Rossing, P; Tarnow, L

    2003-01-01

    OBJECTIVES: Intrauterine growth retardation, as seen in individuals with low weight at birth, may give rise to a reduction in nephron number. Oligonephropathy has been linked to hypertension and renal disease in adult life. We tested the concept that low weight at birth acts as a risk factor...... [R2 (adjusted) = 0.34], whereas birth weight and birth weight/length ratio did not. CONCLUSIONS: Our study does not suggest that weight at birth is associated with progression of established diabetic nephropathy in type 1 diabetic patients, whilst several other potential modifiable risk factors were...... [median (range)] similar to the 134 patients above: 2.6 (-4.7; 9.6) vs. 3.4 (-2.3; 19.3) mL min(-1) year(-1), respectively (NS). A multiple regression analysis revealed that albuminuria, arterial blood pressure, and haemoglobin A1C during follow-up showed a significant correlation with the decline in GFR...

  18. Metabolic control of prevention of nephropathy by 2-tetradecylglycidate in the diabetic mouse (db/db).

    Science.gov (United States)

    Lee, S M; Tutwiler, G; Bressler, R; Kircher, C H

    1982-01-01

    The genetically diabetic mouse (db/db) exhibits hyperphagia, progressive weight gain, hyperglycemia, and hyperinsulinemia during the first few months of life during which time characteristic pathologic changes occur in several organ systems including the kidney. The extent to which long chain fatty acid oxidation (LCFAO) contributes to excessive gluconeogenesis and hyperglycemia in these animals in unknown. Therefore, the synthetic fatty acid analogue 2-tetradeclyglycidate (TDHA), a potent inhibitor of LCFAO, was given orally to db/db mice to evaluate its capacity to control the blood glucose and prevent their diabetic nephropathy. Five groups of diabetic mice (N = 6) were assigned to receive TDGA in a dose of 5, 10, and 25 mg/kg/day, vehicle (tragacanth), or nothing (control). TDGA had no observable effects on food intake or growth patterns. Drug-treated animals had significant lowering of fasting glucose at 0 and 4 h after dosing during the midportion of the study (2-6 wk). In the latter part of the study (wk 8-11), blood glucose 4 h after dosing was lowered in mice given 10 and 25 free fatty acids. Animals receiving TDGA 25 mg/kg/day exhibited significant inhibition of immunopathologic changes in the kidney. Heart weight was significantly increased in mice receiving TDGA 25 mg/kg/day, and the total amount of myocardial carnitine content was increased in all three drug-treated groups. Increased tissue deposition of lipid was not apparent on histologic examination of liver in drug-treated animals. Inhibition of long chain fat oxidation in the db/db mouse results in significant lowering of blood glucose, and decreased the renal immunopathologic features of diabetic nephropathy in this animal model.

  19. Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

    Science.gov (United States)

    Korish, Aida A; Abdel Gader, Abdel Galil; Korashy, Hesham M; Al-Drees, Abdul Majeed; Alhaider, Abdulqader A; Arafah, Maha M

    2015-03-05

    Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy

    NARCIS (Netherlands)

    Boels, M.G.; Koudijs, A.; Avramut, M.C.; Sol, W.; Wang, G.; Oeveren-Rietdijk, A.M. van; Zonneveld, A.J. van; Boer, H.C. de; Vlag, J. van der; Kooten, C. van; Eulberg, D.; Berg, B.M.; DHT, I.J.; Rabelink, T.J.

    2017-01-01

    Inhibition of monocyte chemotactic protein-1 (MCP-1) with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Because the endothelial glycocalyx is also

  1. Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); L. Tarnow; J.M. van Gool (Jeanette); R.J.A. de Bruin (René); F.H.M. Derkx (Frans); M.A.D.H. Schalekamp (Maarten); H.H. Parving

    1999-01-01

    textabstractBACKGROUND: The most striking abnormality in the renin angiotensin system in diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the renin gene has not been studied for

  2. Plasma renin and prorenin and renin gene variation in patients with insulin-dependent diabetes mellitus and nephropathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); L. Tarnow; J.M. van Gool (Jeanette); R.J.A. de Bruin (René); F.H.M. Derkx (Frans); M.A.D.H. Schalekamp (Maarten); H.H. Parving

    1999-01-01

    textabstractBackground. The most striking abnormality in the renin-angiotensin system in diabetic nephropathy (DN) is increased plasma prorenin. Renin is thought to be low or normal in DN. In spite of altered (pro)renin regulation the renin gene has not been studied for contribution to the

  3. Natural antioxidants in the treatment and prevention of diabetic nephropathy; a potential approach that warrants clinical trials.

    Science.gov (United States)

    Al-Waili, Noori; Al-Waili, Hamza; Al-Waili, Thia; Salom, Khelod

    2017-05-01

    Diabetic nephropathy is the major cause of end-stage renal disease and effective and new therapeutic approaches are needed in diabetic nephropathy and chronic kidney diseases. Oxidative stress and inflammatory process are important factors contributing to kidney damage by increasing production of oxidants. KEAP1/Nrf2/ARE pathway regulates the transcription of many antioxidant genes and modulation of the pathway up regulates antioxidants. NFB controls the expression of genes involved in the inflammatory response. Natural substances have antioxidant and anti-inflammatory activities and have an impact on NFB and KEAP1/Nrf2/ARE pathways. The preclinical studies explored the effectiveness of whole herbs, plants or seeds and their active ingredients in established diabetic nephropathy. They ameliorate oxidative stress induced kidney damage, enhance antioxidant system, and decrease inflammatory process and fibrosis; most likely by activating KEAP1/Nrf2/ARE pathway and by deactivating NFB pathway. Whole natural products contain balanced antioxidants that might work synergistically to induce beneficial therapeutic outcome. In this context, more clinical studies involving whole plants or herbal products or mixtures of different herbs and plants and their active ingredients might change our strategies for the management of diabetic nephropathy. The natural products might be useful as preventive interventions and studies are required in this field.

  4. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Mathiesen, E R; Deckert, T

    1986-01-01

    . The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventional-treatment group (median 8.6%, range 7.2-13.4) (p less than 0.001). Clinical diabetic nephropathy (a urinary...

  5. Exposure to DDT and diabetic nephropathy among Mexican Americans in the 1999-2004 National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Everett, Charles J; Thompson, Olivia M; Dismuke, Clara E

    2017-03-01

    Concentrations of the pesticide DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (dichlorodiphenyldichloroethylene), in the blood of Mexican Americans, were evaluated to determine their relationships with diabetes and diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted N = 1,411, population estimate = 13,760,609). The sample included teens, 12-19 years old, which accounted for 19.8% of the data. The time of the study overlapped the banning of DDT in Mexico in the year 2000, and those participants born in Mexico were exposed to DDT before they immigrated to the US. We sought to better understand the relationship of DDT with diabetes in a race/ethnicity group prone to develop diabetes and exposed to DDT. In this study, nephropathy was defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria, and total diabetes was defined as diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥ 6.5%). The proportion with the isomer p,p'-DDT >0.086 ng/g (above the maximum limit of detection) was 13.3% for Mexican Americans born in the US, and 36.9% for those born in Mexico. Levels of p,p'-DDT >0.086 ng/g were associated with total diabetes with nephropathy (odds ratio = 4.42, 95% CI 2.23-8.76), and with total diabetes without nephropathy (odds ratio = 2.02, 95% CI 1.19-3.44). The third quartile of p,p'-DDE (2.99-7.67 ng/g) and the fourth quartile of p,p'-DDE (≥7.68 ng/g) were associated with diabetic nephropathy and had odds ratios of 5.32 (95% CI 1.05-26.87) and 14.95 (95% CI 2.96-75.48) compared to less than the median, respectively, whereas p,p'-DDE was not associated with total diabetes without nephropathy. The findings of this study differ from those of a prior investigation of the general adult US population in that there were more associations found with the Mexican Americans sample. Published by Elsevier Ltd.

  6. Influence of Enalapril on the progression of chronic renal failure in diabetic nephropathy and nephropathies of and other aethiology: A two-year study

    Directory of Open Access Journals (Sweden)

    Trbojević Jasna

    2002-01-01

    Full Text Available Chronic renal failure (CRF is almost always associated with high arterial blood pressure. Adequate control of hypertension slows down the progression of the disease, Inhibitors of angiotenzin-converting enzyme (ACE inhibitors have proved to be very efficacious in decreasing high blood pressure. The aim of this study was to assess the influence of ACE inhibitor enalapril on the progression of CRF in patients with diabetic nephropathy and nephropathies of other origin. During 1998 and 1999 thirty patients (20 males and 10 females, aged 525+1.3 have been followed-up at the Department of Nephrology, Clinical Centre of Serbia. On regular monthly controls serum creatinine, urea, calcium and protein levels, creatinine clearance, and blood pressure, were measured. All patients were suggested a low protein diet. Progression of the disease was expressed by the slope of the regression line showing reciprocal serum creatinine values. Proteinaemia was significantly higher in diabetic patients after 12 months (p<0.35 but in the next 12 months the difference between groups disappeared. The same patients had significantly lower serum urea (p<0.05 after 24 months and creatinine values (p<0.05 dur ing the whole study. Other variables changed in the same manner and with similar progression in both groups. The direction of slope lines suggested recovery of kidney function in both examined groups. However, a smaller slope in patients with diabetic nephropathy together with other results showed that enalapril had better influence on slowing down the progression of CRF in this group of patients.

  7. Management of Madhumeha Janya Upadrava with special reference to diabetic nephropathy - A clinical study.

    Science.gov (United States)

    Akarshini, A M; Aruna

    2014-01-01

    Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. As the disease DN manifests secondary to Madhumeha, the disease is termed as Madhumeha Janya Upadrava. The diagnosis of DN is microalbuminuria is a powerful screening tool in screening DN earlier stages. A diabetic can develop nondiabetic renal disease like anyone, but the finding of diabetic retinopathy strongly suggests that any proteinuria is due to diabetic glomerulosclerosis. In this dissertation, all diabetic patients who showed positive diabetic retinopathy changes; were screened for 24 h microalbuminuria, at its earlier asymptomatic period itself. This research work is specially intended to instigate effective therapies at earlier stage itself, thereby prevent further progression. To evaluate the combined effect of Shilajitvadi Vataka, Punarnavadi Mandura, Triphala Guggulu and Pippalimooladi Paneeya added with Amrita and Bringaraja in DN. Single blind clinical study with pre-test and post-test was designed. The study conducted on 15 patients of both sex aged between 20 and 80 years, having DN changes through assays for microalbuminuria and other biochemical assays; along with prior confirmation of diabetic retinopathy changes. The duration of the study was 48 days and patients were assessed on every 15 days. After 48 days of treatment, statistically significant improvement in levels of microalbuminuria with mean difference 83.76 μg/24 h, highly significant improvement in status of Agni and statistically no significant improvement in glomerular filtration rate by 2.381 mL/min/1.73m(2). No significant side-effects were observed. Overall the study showed encouraging results in treating the malady DN.

  8. Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

    Science.gov (United States)

    Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

    2018-01-01

    There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were

  9. Controversial effects of Calendula officinalis L. on Biochemical and Pathological Factors of Nephropathy in Diabetic Wistar Rats

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    Salehi

    2015-07-01

    Full Text Available Background Chronic hyperglycemia leads to microvascular and macrovascular complications such as diabetic nephropathy. Medicinal plants are good sources for finding new therapeutic chemicals to improve diabetes and relieve its symptoms. Objectives The purpose of the present study was to evaluate the effect of the hydroalcoholic extract (300 mg/kg of Calendula officinalis (marigold on blood biochemical profiles and histopathological changes in kidney of streptozotocin-induced diabetic rats. Materials and Methods Twenty male Wistar rats were divided to four groups: Normal control (NC, diabetic control (DC, normal C. officinalis (N+CO 300 mg/kg, and diabetic C. officinalis (D+CO 300 mg/kg. The rats were treated for a period of 13 weeks. Diabetes was induced by Streptozocin injection, intraperitoneally. Level of glucose, urea, creatinine and also total anti-oxidant capacity, malondialdehyde, total oxidant status in serum and histological alterations in the kidney were analyzed. Results Level of serum glucose, urea, creatinine, malondialdehyde and total oxidant status were increased in diabetic rats, whereas, total anti-oxidant capacity was decreased compared to the control animals. Also, histological findings confirmed the absence of integrity in glomerulus and mass infiltration in kidney tissue in diabetic rats compared to the normal controls. Calendula officinalis extract had no effect on blood glucose, but it decreased blood urea nitrogen and creatinine, total oxidant status and malondialdehyde while it increased total anti-oxidant capacity in the diabetic extract-treated group when compared to diabetic rats. Calendula officinalis could not prevent nephropathy changes in the diabetic rats. Conclusions Therefore, our results suggest that although administration of 300 mg/kg of Calendula officinalis extract showed salutary effects on anti-oxidant profile, yet its protective effects on anti-diabetic and regenerative properties on nephropathy were

  10. Effect of direct renin inhibitor monotherapy on proteinuria in overt diabetic nephropathy.

    Science.gov (United States)

    Silaratana, Somrutat; Sumransurp, Sangduen; Duangchana, Soodkate; Tasanarong, Adis

    2012-01-01

    Diabetic nephropathy is one of the major causes of chronic kidney disease (CKD), consequently progression to end stage renal disease. The previous studies demonstrated that the inhibition on renin-angiotensin-aldosterone system (RAAS) such as by angiotensin converting enzyme inhibitor (ACEI) and angiotensin type I receptor blocker (ARB) reduced proteinuria and slow progression of CKD. Direct renin inhibitor (DRI) theoretical complete block RAAS by reducing plama renin activity angiotensin I and angiotensin II. The present study aimed to determine the efficacy of aliskiren (DRI) monotherapy on blood pressure control and proteinuria reduction. Diabetic mellitus patients with estimated glomerular filtration rate (eGFR) > or = 30 ml/min who had proteinuria > 300 mg/day were enrolled to receive aliskiren 150 mg/day for 2 weeks then 300 mg/day until 24 weeks. The SBP were significantly decreased form 137.8 to 123.7 (p = 0.01) at 2 weeks, 137.8 to 126.26 (p = 0.04) at 4 weeks and 137.8 to 121 mmHg (p = 0.002) at 24 weeks after treatment, respectively. Similar to SBP, the DBP was significantly decreased from 84.08 to 73.66 (p = 0.04) at 4 weeks and 84.08 to 75.85 mmHg (p = 0.002) at the end of study. Reduction of UPCR showed significantly reduced for 32.65% (p = 0.007) and 45% (p = 0.004) from baseline at 2 weeks and 24 weeks after DRI treatment respectively. Serum creatinine, eGFR and serum potassium were no significant changed from the baseline. There were no harmful adverse reaction in patients who receiving aliskirin. Aliskiren monotherapy showed significantly reduced proteinuria, good blood pressure control without harmful side effect in overt diabetic nephropathy patients.

  11. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, Tri Q; Tarnow, Lise; Jorsal, Anders

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic...

  12. Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice

    Science.gov (United States)

    2012-01-01

    Background In the present study, we examined the antioxidant effect of water soluble derivative of propolis (WSDP) and ethanolic (EEP) extract of propolis on renal and liver function in alloxan-induced diabetic mice. In addition, we examined whether different extract of propolis could prevent diabetic nephropathy and liver toxicity by inhibiting lipid peroxidation in vivo. Methods Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg-1). Two days after alloxan injection, propolis preparations (50 mg kg-1 per day) were given intraperitoneally for 7 days in diabetic mice. Survival analysis and body weights as well as hematological and biochemical parameters were measured. The renal and liver oxidative stress marker malonaldehyde levels and histopathological changes were monitored in the liver and kidney of treated and control mice. Results Administration of propolis to diabetic mice resulted in a significant increase of body weight, haematological and immunological parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected mice showed a marked increase in oxidative stress in liver and kidney homogenate, as determined by lipid peroxidation. Histopathological observation of the liver sections of alloxan-induced diabetic mice showed several lesions including cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations, but with individual variability.Treatment of diabetic mice with propolis extracts results in decreased number of vacuolized cells and degree of vacuolization; propolis treatment improve the impairment of fatty acid metabolism in diabetes. Renal histology showed corpuscular, tubular and interstitial changes in alloxan-induced diabetic mice. Test components did not improve renal histopathology in diabetic mice. Conclusions Propolis preparations are able to attenuate diabetic hepatorenal damage, probably through its anti-oxidative action and its detoxification

  13. Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice

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    Oršolić Nada

    2012-08-01

    Full Text Available Abstract Background In the present study, we examined the antioxidant effect of water soluble derivative of propolis (WSDP and ethanolic (EEP extract of propolis on renal and liver function in alloxan-induced diabetic mice. In addition, we examined whether different extract of propolis could prevent diabetic nephropathy and liver toxicity by inhibiting lipid peroxidation in vivo. Methods Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg-1. Two days after alloxan injection, propolis preparations (50 mg kg-1 per day were given intraperitoneally for 7 days in diabetic mice. Survival analysis and body weights as well as hematological and biochemical parameters were measured. The renal and liver oxidative stress marker malonaldehyde levels and histopathological changes were monitored in the liver and kidney of treated and control mice. Results Administration of propolis to diabetic mice resulted in a significant increase of body weight, haematological and immunological parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected mice showed a marked increase in oxidative stress in liver and kidney homogenate, as determined by lipid peroxidation. Histopathological observation of the liver sections of alloxan-induced diabetic mice showed several lesions including cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations, but with individual variability.Treatment of diabetic mice with propolis extracts results in decreased number of vacuolized cells and degree of vacuolization; propolis treatment improve the impairment of fatty acid metabolism in diabetes. Renal histology showed corpuscular, tubular and interstitial changes in alloxan-induced diabetic mice. Test components did not improve renal histopathology in diabetic mice. Conclusions Propolis preparations are able to attenuate diabetic hepatorenal damage, probably through its anti-oxidative action and

  14. Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy.

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    Kim, Bo Hwan; Lee, Eun Soo; Choi, Ran; Nawaboot, Jarinyaporn; Lee, Mi Young; Lee, Eun Young; Kim, Hyeon Soo; Chung, Choon Hee

    2016-05-01

    Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

  15. NLRP3 expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients.

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    El-Horany, Hemat El-Sayed; Abd-Ellatif, Rania Nagi; Watany, Mona; Hafez, Yasser M; Okda, Hanaa Ibrahim

    2017-08-01

    Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN. Forty-five type 2 diabetic patients: 15 normoalbuminuric, 15 microalbuminuric, 15 macroalbuminuric, in addition to 15 healthy controls were enrolled in this study. Clinical examination and routine laboratory investigations were performed. NLRP3 mRNA expression was assessed by real time polymerase chain reaction. Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin 1β (IL-1β), and uHSP72 levels were estimated by enzyme-linked immunosorbent assay. Serum chitotriosidase (CHIT1) activity was examined. NLRP3 mRNA relative expression, serum levels of 8-OHdG, IL-1β, and uHSP72, in addition to CHIT 1 activity were significantly increased in the macroalbuminuric patient group as compared to control and the other two diabetic groups. Also, a significant positive correlation was documented between the previously mentioned parameters and urinary albumin/creatinine ratio, serum creatinine, and HbA1c. Multiple linear regression analysis using urinary albumin/creatinine ratio as dependent variable confirmed that uHSP72 and NLRP3 mRNA relative expression were the independent predictors of DN (β were 0.432 and 0.448 respectively, P NLRP3 mRNA relative expression and uHSP72 levels were useful biomarkers discriminating DN patients from patients with type 2 diabetes mellitus (AUC were 0.957 and 0.983, respectively). uHSP72 may

  16. Improvement of renal oxidative stress markers after ozone administrationin diabetic nephropathy in rats

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    Morsy Mohamed D

    2010-05-01

    Full Text Available Abstract Background Several complications of diabetes mellitus (DM e.g. nephropathy (DN have been linked to oxidative stress. Ozone, by means of oxidative preconditioning, may exert its protective effects on DN. Aim The aim of the present work is to study the possible role of ozone therapy in ameliorating oxidative stress and inducing renal antioxidant defence in streptozotocin (STZ-induced diabetic rats. Methods Six groups (n = 10 of male Sprague Dawley rats were used as follows: Group C: Control group. Group O: Ozone group, in which animals received ozone intraperitoneally (i.p. (1.1 mg/kg. Group D: Diabetic group, in which DM was induced by single i.p. injections of streptozotocin (STZ. Group DI: Similar to group D but animals also received subcutaneous (SC insulin (0.75 IU/100 gm BW.. Group DO: In which diabetic rats received the same dose of ozone, 48 h after induction of diabetes. Group DIO, in which diabetic rats received the same doses of insulin and ozone, respectively. All animals received daily treatment for six weeks. At the end of the study period (6 weeks, blood pressure, blood glycosylated hemoglobin (HbA1c, serum creatinine, blood urea nitrogen (BUN, kidney tissue levels of superoxide dismutase (SOD, catalase (CAT, glutathione peroxide (GPx, aldose reductase (AR activities and malondialdehyde (MDA concentration were measured. Results Induction of DM in rats significantly elevated blood pressure, HbA1c, BUN, creatinine and renal tissue levels of MDA and AR while significantly reducing SOD, CAT and GPx activities. Either Insulin or ozone therapy significantly reversed the effects of DM on all parameters; in combination (DIO group, they caused significant improvements in all parameters in comparison to each alone. Conclusions Ozone administration in conjunction with insulin in DM rats reduces oxidative stress markers and improves renal antioxidant enzyme activity which highlights its potential uses in the regimen for treatment of

  17. Protective effects of allicin on streptozotocin-induced diabetic nephropathy in rats.

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    Huang, Hong; Jiang, Ying; Mao, Genxiang; Yuan, Fang; Zheng, Hexin; Ruan, Yuan; Wu, Tianfeng

    2017-03-01

    Studies in animal models have shown that allicin, a major biologically active component of garlic, can play a role in the prevention of tissue fibrosis in the liver, lung and heart, mainly related to the inhibition of fibroblast proliferation, fibrogenic cytokine secretion and extracellular matrix synthesis. This study aimed to investigate the protective effects of allicin on renal damage in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were administered allicin (15, 30 and 45 mg · kg -1  · day -1 ) via daily intra-gastric gavage for 12 weeks. The levels of fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (sCr), lipid and 24 h urine albumin excretion (UAE) were measured at the end of weeks 4, 8 and 12. The renal histopathology and the expression levels of collagen I, transforming growth factor β1 (TGF-β1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were measured using immunohistochemistry and/or western blotting. In 12 week STZ-induced diabetic rats, severe hyperglycemia and albuminuria were markedly developed. Treatment with allicin for 12 weeks ameliorated diabetes-induced morphological alterations of the kidney and decreased FBG, BUN, sCr, triglyceride (TG) and 24 h UAE in diabetic rats. The expression levels of collagen I, TGF-β1 and p-ERK1/2 were significantly decreased by allicin treatment. These results suggested that allicin may play a protective role in diabetic nephropathy via the TGF-β1/ERK pathway in diabetic rats. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  18. Histone Acetylation and Its Modifiers in the Pathogenesis of Diabetic Nephropathy

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    Xiaoxia Li

    2016-01-01

    Full Text Available Diabetic nephropathy (DN remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors contributing to DN is required to develop more effective therapeutic options. It is becoming more evident that histone acetylation (HAc, as one of the epigenetic mechanisms, is thought to be associated with the etiology of diabetic vascular complications such as diabetic retinopathy (DR, diabetic cardiomyopathy (DCM, and DN. Histone acetylases (HATs and histone deacetylases (HDACs are the well-known regulators of reversible acetylation in the amino-terminal domains of histone and nonhistone proteins. In DN, however, the roles of histone acetylation (HAc and these enzymes are still controversial. Some new evidence has revealed that HATs and HDACs inhibitors are renoprotective in cellular and animal models of DN, while, on the other hand, upregulation of HAc has been implicated in the pathogenesis of DN. In this review, we focus on the recent advances on the roles of HAc and their covalent enzymes in the development and progression of DN in certain cellular processes including fibrosis, inflammation, hypertrophy, and oxidative stress and discuss how targeting these enzymes and their inhibitors can ultimately lead to the therapeutic approaches for treating DN.

  19. Novel Actions of Growth Hormone in Podocytes: Implications for Diabetic Nephropathy

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    Dhanunjay Mukhi

    2017-07-01

    Full Text Available The kidney regulates water, electrolyte, and acid-base balance and thus maintains body homeostasis. The kidney’s potential to ensure ultrafiltered and almost protein-free urine is compromised in various metabolic and hormonal disorders such as diabetes mellitus (DM. Diabetic nephropathy (DN accounts for ~20–40% of mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates injury to the glomerular filtration barrier (GFB. The GFB is composed of glomerular endothelium, basement membrane, and podocytes. Podocytes are terminally differentiated epithelial cells with limited ability to replicate. Podocyte shape and number are both critical for the integrity and function of the GFB. Podocytes are vulnerable to various noxious stimuli prevalent in a diabetic milieu that could provoke podocytes to undergo changes to their unique architecture and function. Effacement of podocyte foot process is a typical morphological alteration associated with proteinuria. The dedifferentiation of podocytes from epithelial-to-mesenchymal phenotype and consequential loss results in proteinuria. Poorly controlled type 1 DM is associated with elevated levels of circulating growth hormone (GH, which is implicated in the pathophysiology of various diabetic complications including DN. Recent studies demonstrate that functional GH receptors are expressed in podocytes and that GH may exert detrimental effects on the podocyte. In this review, we summarize recent advances that shed light on actions of GH on the podocyte that could play a role in the pathogenesis of DN.

  20. Urinary N-acetyl B glucosaminidase as an earlier marker of diabetic nephropathy and influence of low-dose perindopril/indapamide combination.

    Science.gov (United States)

    Basturk, T; Altuntaş, Y; Kurklu, A; Aydin, L; Eren, N; Unsal, A

    2006-01-01

    Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. N-Acetyl B glucosaminidase (NAG) is derived from proximal tubular cells and is widely used to evaluate tubular renal function. The objective of this study is whether NAG can be used as an early marker of diabetic nephropathy by comparing the urinary NAG levels between healthy controls and diabetic patients and determining changes in urinary NAG excretion after treatment with low-dose combination perindopril (2 mg)/ indapamide (0.625 mg)/o.d. A total of 50 patients (29 female) with type II diabetes mellitus applying to our diabetes outpatient clinics for the first time were included in our study (Group 1). Diabetic patients were classified into three subgroups on the basis of their duration of diabetes: Group 1A (n = 15) 5 years. The inclusion criteria were no prior use of antihypertensive agents; blood pressure Systolic and diastolic blood pressures, HbA1c, body mass index, 24-h microalbuminuria (MAU), and NAG measurements in urine samples were performed by using colorimetric assay method in an analyzer (Roche Cobas Mira). The assay defined as fragmentation of 3-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide molecule by NAG to 3-cresolsulphonphthalein and N-acetylglucosamine molecules and serum creatinine were measured in all groups. Type II diabetic patients were administered perindopril (2 mg)/indapamide (0.625 mg) combination once daily for 4 months, and urinary NAG levels were measured at the end of treatment. Statistically significant differences were observed between the groups 1 and 2 with respect to the levels of NAG and HbA1c (p 0.05). In diabetic patients, pretreatment NAG were lowest in Group 1A and highest in Group 1c, although the difference between the treatment subgroups was not statistically significant (p > 0.05). Urinary NAG excretion is elevated in type II diabetic patients as compared with the healthy individuals

  1. Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

    Science.gov (United States)

    Yadav, Ashok K; Sinha, Nisha; Kumar, Vinod; Bhansali, Anil; Dutta, Pinaki; Jha, Vivekanand

    2016-07-01

    CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to ß-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

  2. The CNDP1 (CTG5 Polymorphism Is Associated with Biopsy-Proven Diabetic Nephropathy, Time on Hemodialysis, and Diabetes Duration

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    Thomas Albrecht

    2017-01-01

    Full Text Available Considering that the homozygous CNDP1 (CTG5 genotype affords protection against diabetic nephropathy (DN in female patients with type 2 diabetes, this study assessed if this association remains gender-specific when applying clinical inclusion criteria (CIC-DN or biopsy proof (BP-DN. Additionally, it assessed if the prevalence of the protective genotype changes with diabetes duration and time on hemodialysis and if this occurs in association with serum carnosinase (CN-1 activity. Whereas the distribution of the (CTG5 homozygous genotype in the no-DN and CIC-DN patients was comparable, a lower frequency was found in the BP-DN patients, particularly in females. We observed a significant trend towards high frequencies of the (CTG5 homozygous genotype with increased time on dialysis. This was also observed for diabetes duration but only reached significance when both (CTG5 homo- and heterozygous patients were included. CN-1 activity negatively correlated with time on hemodialysis and was lower in (CTG5 homozygous patients. The latter remained significant in female subjects after gender stratification. We confirm the association between the CNDP1 genotype and DN to be likely gender-specific. Although our data also suggest that (CTG5 homozygous patients may have a survival advantage on dialysis and in diabetes, this hypothesis needs to be confirmed in a prospective cohort study.

  3. Value of ambulatory blood pressure monitoring in type I (insulin-dependent) diabetic patients with incipient diabetic nephropathy.

    Science.gov (United States)

    Berrut, G; Hallab, M; Bouhanick, B; Chameau, A M; Marre, M; Fressinaud, P

    1994-03-01

    Ambulatory blood pressure monitoring (ABPM) is currently proposed for measuring blood pressure in type I, insulin-dependent diabetic subjects with incipient diabetic nephropathy. However, the value of this method, in comparison with conventional ones in detecting blood pressure differences between normotensive type I, insulin-dependent diabetic subjects with or without microalbuminuria, is questionable. We obtained systolic, diastolic, and mean blood pressures (SBP/DBP/MBP) in 10 hospitalized normotensive type I, insulin-dependent diabetic subjects with microalbuminuria, and in 29 others without, using a mercury sphygmomanometer (method 1) and an automatic device (Dinamap; method 2) to obtain morning (9 to 11 AM) measurements, and ABPM (SpaceLabs 90207; method 3) to obtain daytime (7 AM to 10 PM) and nighttime (10 PM to 7 AM) measurements. During the daytime, SBP/DBP/MBP values were higher in microalbuminuric than in normoalbuminuric patients, whatever the blood pressure measurement method used (P = .034/.061/.033, two-factor ANOVA). Analysis of 24-h ABPM also showed higher SBP/DBP/MBP in microalbuminuric than in normoalbuminuric patients (P = .022/.040/.016), and demonstrated a defect in nocturnal SBP decrease in microalbuminuric compared with normoalbuminuric patients (P = .028). Stepwise multiple regression analysis indicated nocturnal SBP as the only independent factor determining for microalbuminuria (F = 6.72). Thus ABPM, in relation to other methods, indicates above all that the most relevant blood pressure change in type I insulin-dependent diabetic subjects with microalbuminuria is a defect in nocturnal SBP decrease.

  4. Family-based association analysis confirms the role of the chromosome 9q21.32 locus in the susceptibility of diabetic nephropathy.

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    Marcus G Pezzolesi

    Full Text Available A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted P = 0.222]. When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P = 1.42×10(-3 [adjusted P = 0.009]. This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192] and in analyses expanded to include all relatives (P = 0.019 [adjusted P = 0.114]. These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci.

  5. Impact of arterial blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients

    DEFF Research Database (Denmark)

    Rossing, P; Hommel, E; Smidt, U M

    1993-01-01

    To evaluate the impact of systemic blood pressure and albuminuria on the progression of diabetic nephropathy, we followed 41 IDDM patients with persistent albuminuria (> 300 mg/24 h) by measuring glomerular filtration rate (51Cr-EDTA technique), blood pressure, and albuminuria. None of the patients...... were taking drugs other than insulin. Arterial blood pressure, albuminuria, and blood glucose were measured four to eight times/yr, whereas glomerular filtration rate was determined twice yearly. During the median investigation period of 36 (15-66) mo, glomerular filtration rate decreased from 102...... +/- 23 to 83 +/- 27 ml.min-1 x 1.73 m-2 (P albuminuria increased from 633 to 1435 micrograms/min (P

  6. A Glimpse of the Pathogenetic Mechanisms of Wnt/β-Catenin Signaling in Diabetic Nephropathy

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    Li Xiao

    2013-01-01

    Full Text Available The Wnt family of proteins belongs to a group of secreted lipid-modified glycoproteins with highly conserved cysteine residues. Prior results indicate that Wnt/β-catenin signaling plays a prominent role in cell differentiation, adhesion, survival, and apoptosis and is involved in organ development, tumorigenesis, and tissue fibrosis, among other functions. Accumulating evidence has suggested that Wnt/β-catenin exhibits a pivotal function in the progression of diabetic nephropathy (DN. In this review, we focused on discussing the dual role of Wnt/β-catenin in apoptosis and epithelial mesenchymal transition (EMT formation of mesangial cells. Moreover, we also elucidated the effect of Wnt/β-catenin in podocyte dysfunction, tubular EMT formation, and renal fibrosis under DN conditions. In addition, the molecular mechanisms involved in this process are introduced. This information provides a novel molecular target of Wnt/β-catenin for the protection of kidney damage and in delay of the progression of DN.

  7. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice.

    Science.gov (United States)

    Saravanan, Settu; Pari, Leelevinothan

    2016-02-05

    Obesity is one of several factors implicated in chronic kidney disease (CKD). Thymol, a monoterpene phenolic compound found in the oils of thyme with multiple biological properties especially antidiabetic activity. The present study was undertaken to evaluate the thymol against diabetic nephropathy by high fat diet (HFD)-induced diabetic C57BL/6J mice. After 10 weeks of continuous dietary intervention, HFD (fat- 35.2%) to mice presented characteristic features of progressive nephropathy by significant increased in kidney weight, blood, and urinary parameters, glomerulosclerosis, oxidative stress, hyperlipidemia and subsequent renal injuries. After intragastric administration of thymol (40 mg/kg BW) daily for the subsequent 5 weeks significantly decreased the blood, urinary parameters and kidney weight. Thymol inhibited the activation of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF). Also, significantly increased the antioxidants and suppresses the lipid peroxidation markers in erythrocytes and kidney tissue compared to the diabetic mice. Thymol downregulated the expression level of sterol regulatory element binding protein-1c (SREBP-1c) and reduced the lipid accumulation in renal. Histopathological study of kidney tissues showed that extracellular mesangial matrix expansion, glomerulosclerosis in diabetic mice were suppressed by thymol. Further, our results indicate that administration of thymol afforded remarkable protection against HFD-induced diabetic nephropathy. Copyright © 2015. Published by Elsevier Ireland Ltd.

  8. Attenuation of Diabetic Nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF Rats with a Combination of Chinese Herbs (Tangshen Formula

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    Haojun Zhang

    2011-01-01

    Full Text Available Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula on diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model.

  9. Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Hovind, P; Tarnow, L; Oestergaard, P B

    2000-01-01

    with nephropathy as compared to the normoalbuminuric group; (median [range]): 45.7 [22.0-410] versus 27.1 [22.0-355] ng/L, respectively, P 0.001. This difference was ascribed to elevated VEGF levels in nephropathic men: 51.8 [22.0-410] versus 22.0 [22.0-308] ng/L, P 0. 001. No differences were found between...... women with and without nephropathy: 37.8 [22.0-325] versus 36.6 [22.0-335] ng/L, NS. In proteinuric patients with GFR above and below the median value, there was no difference in the level of VEGF, NS. Plasma VEGF was below the detection limit (22.0 ng/L) in 60 patients with nephropathy and 93 patients...... with normoalbuminuria, P 0.001. The mean rate of GFR decline was 3.5 (SE: 0.4) mL/min/year, and the following baseline variables acted as predictors of progression: albuminuria, mean arterial blood pressure and male gender. Hemoglobin A1c and plasma VEGF did not act as predictors. No significant differences between...

  10. The plasma osteoprotegerin level and osteoprotegerin expression in renal biopsy tissue are increased in type 2 diabetes with nephropathy.

    Science.gov (United States)

    Wang, S-T; Zhang, C-Y; Zhang, C-M; Rong, W

    2015-02-01

    To investigate the plasma osteoprotegerin level and osteoprotegerin expression in renal biopsy tissue in type 2 diabetes with nephropathy. Plasma osteoprotegerin level was measured by enzyme-linked immunoassay in 48 type 2 diabetes with normoalbuminuria, 48 patients with microalbuminuria, 44 patients with macroalbuminuria and 40 healthy persons. Part of diabetes patients with nephropathy were performed kidney biopsy by ultrasound guide. The osteoprotegerin expression in kidney biopsy tissue is examined by immunohistochemistry. The plasma osteoprotegerin levels were significantly elevated in patients with microalbuminuria (3.73±0.75 ng/l) and macroalbuminuria (4.68±0.82 ng/l) as compared with patients with normoalbuminuria (2.71±0.69 ng/l) and control subjects (2.11±0.42 ng/l). And the plasma osteoprotegerin level in macroalbuminuric group was also higher than that in microalbuminuria group. The plasma osteoprotegerin level had a positive correlation with the fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glycohemoglobinA1c (HbA1C), high sensitive C-reactive protein (hsCRP) and log(UAER). Multivariate regression analysis revealed that plasma osteoprotegerin level was an independent factor associated with albuminuria in type 2 diabetes. The immunohistochemistry results showed that positive immunostaining for osteoprotegerin was observed in the renal tubule cells of biopsy and not in glomerulus, and the osteoprotegerin expression was higher in macroalbuminuria group than that in microalbuminuria group. The plasma osteoprotegerin level and the osteoprotegerin expression in renal tubule cells of biopsy tissue were increased in nephropathy of type 2 diabetes. This finding supports the growing concept that osteoprotegerin may act as an important regulatory molecule in the angiopathy, and particularly, that it may be involved in the occurrence and development of nephropathy in type 2 diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Chaperonin-Containing t-Complex Protein-1 Subunit β as a Possible Biomarker for the Phase of Glomerular Hyperfiltration of Diabetic Nephropathy

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    Chung-Ze Wu

    2015-01-01

    Full Text Available In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β and early diabetic nephropathy (DN. In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM. To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (Ccr, and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that Ccr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.

  12. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

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    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  13. Combined losartan and nitro-oleic acid remarkably improves diabetic nephropathy in mice

    Science.gov (United States)

    Liu, Ying; Jia, Zhanjun; Liu, Shanshan; Downton, Maicy; Liu, Gang; Du, Yaomin

    2013-01-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). The inhibitors of renin-angiotensin-aldosterone system (RAAS) can alleviate some of the symptoms of DN but fail to stop the progression to ESRD. Our previous studies demonstrate renoprotective action of nitro-oleic acid (OA-NO2) in several rodent models of renal disease. Here we examined the therapeutic potential and the underlying mechanism of combination of losartan and OA-NO2 in db/db mice. OA-NO2 was infused at 5 mg·kg−1·day−1 via osmotic minipump, and losartan was incorporated into diet at 10 mg·kg−1·day−1, each administered alone or in combination for 2 wk. Diabetic db/db mice developed progressive albuminuria and glomerulosclerosis, accompanied by podocytes loss, increased indexes of renal fibrosis, oxidative stress, and inflammation. Treatment of the diabetic mice with OA-NO2 or losartan alone moderately ameliorated kidney injury; however, the combined treatment remarkably reduced albuminuria, restored glomerular filtration barrier structure, and attenuated glomerulosclerosis, accompanied with significant suppression of renal oxidative stress and inflammation. These data demonstrate that combination of losartan and OA-NO2 effectively reverses renal injury in DN. PMID:23946292

  14. IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives.

    Science.gov (United States)

    Feigerlová, Eva; Battaglia-Hsu, Shyue-Fang

    2017-10-01

    Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

    Science.gov (United States)

    Yuan, Hongping; Zhang, Xiaoxuan; Zheng, Wei; Zhou, Hui; Zhang, Bo-Yin; Zhao, Dongxu

    2016-01-01

    The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis.

  16. The PPAR gamma 2 Pro12Ala variant predicts ESRD and mortality in patients with type 1 diabetes and diabetic nephropathy

    DEFF Research Database (Denmark)

    Jorsal, A; Tarnow, L; Lajer, M

    2008-01-01

    The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma 2 gene is suggested to associate with diabetic nephropathy and cardiovascular disease in type 2 diabetes. The aim of this study was to investigate the polymorphism in relation to diabetic nephropathy, end-stage renal...... frequencies (p=0.25). Cox regression analysis revealed a covariate-adjusted hazard ratio (HR) for all-cause mortality in patients with the Ala/Ala genotype of 2.44 (1.23-4.84). The Pro12Ala polymorphism did not predict CVD events. However, the Ala/Ala genotype predicts ESRD (covariate-adjusted HR 2.60 (1.......11-6.07)). Furthermore, Carriers of the Ala-allele had a higher rate of decline in GFR (p=0.040). In conclusion, the Pro12Ala polymorphism is not associated with type 1 diabetic nephropathy. The Ala-allele is associated with enhanced decline in GFR and predicts ESRD and all-cause mortality in patients with nephropathy....

  17. PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Jacobsen, Peter; Grarup, Niels; Tarnow, Lise

    2002-01-01

    Recently, an amino acid variant (K121Q) in the glycoprotein PC-1 (Q allele) has been associated with faster progression of diabetic nephropathy, as estimated by calculated creatinine clearance. We tested the impact of the PC-1 (K121Q) variant on loss of glomerular filtration rate (GFR) measured...

  18. Relative Incidence of ESRD Versus Cardiovascular Mortality in Proteinuric Type 2 Diabetes and Nephropathy : Results From the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) Database

    NARCIS (Netherlands)

    Packham, David K.; Alves, Tahira P.; Dwyer, Jamie P.; Atkins, Robert; de Zeeuw, Dick; Cooper, Mark; Shahinfar, Shahnaz; Lewis, Julia B.; Lambers Heerspink, Hiddo J.

    Background: Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome

  19. Plasma high-sensitivity troponin T predicts end-stage renal disease and cardiovascular and all-cause mortality in patients with type 1 diabetes and diabetic nephropathy

    DEFF Research Database (Denmark)

    Galsgaard, Julie; Persson, Frederik; Hansen, Tine Willum

    2017-01-01

    factors, including NT-proBNP and hsCRP, the hazard ratio for ESRD at 1.26 was not significant in the diabetic nephropathy group, but there was a significant association with GFR decline after adjustment during follow-up (2.9 ml/min/1.73 m(2) annual decline per doubling in hsTnT). The unadjusted...

  20. Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.

    Science.gov (United States)

    Mahfoz, Amal M; El-Latif, Hekma A Abd; Ahmed, Lamiaa A; Hassanein, Nahed M; Shoka, Afaf A

    2016-12-01

    Since chronic kidney disease due to diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are desperately needed. In the present study, the anti-diabetic and renoprotective effects of aliskiren have been evaluated in streptozotocin (STZ)-induced DN in rats. DN was induced by a single intraperitoneal injection of STZ (65 mg/kg). Three weeks after STZ, rats were divided into four groups; normal, diabetic, diabetic treated with gliclazide (10 mg/kg/day) for 1 month, and diabetic treated with aliskiren (50 mg/kg/day) for 1 month. At the end of the experiment, mean arterial blood pressure and heart rate were recorded. Rats were then euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin, and tumor necrosis factor-alpha (TNF-α). One kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) contents. Other kidney was used for histopathological study and immunohistochemical measurement of caspase-3 and transforming growth factor beta (TGF-β). In addition, islets of Langerhans were isolated from normal rats by collagenase digestion technique for in vitro study. Aliskiren normalized STZ-induced hyperglycemia, increased insulin level both in vivo and in vitro, normalized kidney function tests and blood pressure, and alleviated STZ-induced kidney histopathological changes. This could be related to the ability of aliskiren toward preserving hemodynamic changes and alleviating oxidative stress and inflammatory and apoptotic markers induced by STZ in rats. However, aliskiren was more effective than gliclazide in relieving STZ-induced DN. These findings support the beneficial effect of aliskiren treatment in DN which could be attributed to its anti-diabetic, renoprotective, antioxidant, anti-inflammatory, and anti-apoptotic effects. Moreover, clinical studies are required to establish the

  1. Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia.

    Directory of Open Access Journals (Sweden)

    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.

  2. PECAM-1 Leu125Val (rs688 Polymorphism and Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Matej Završnik

    2016-01-01

    Full Text Available Objectives. Platelet endothelial cell adhesion molecule-1 (PECAM-1 plays a key role in the transendothelial migration of circulating leukocytes during inflammation and in the maintenance of vascular endothelial integrity. We hypothesized that genetic variation in PECAM-1 gene could be associated with diabetic nephropathy (DN and with the level of soluble PECAM-1 in Caucasians with type 2 diabetes mellitus (T2DM. Design and Methods. We analyzed the rs688 single nucleotide polymorphism of PECAM-1 gene C373G (Leu125Val at exon 3, which encodes the first extracellular Ig-like domain that mediates the homophilic binding of PECAM-1, in 276 T2DM subjects with documented DN (cases and 375 T2DM subjects without DN (controls, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy. Level of plasma soluble PECAM-1 (sPECAM-1 was measured by ELISA in a subpopulation of 120 diabetics with DN. Results. We found no association between the Leu125Val polymorphism and DN in subjects with T2DM. Likewise, the Leu125Val polymorphism was not associated with serum sPECAM-1 levels in a subpopulation of 120 diabetics with DN. Conclusion. The Leu125Val polymorphism of PECAM-1 and the level of sPECAM-1 are not associated with DN in T2DM subjects of Slovenian origin.

  3. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jie, E-mail: jiezhang@dicp.ac.cn [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Yan Lijuan [XiaMen Entry-Exit Inspection and Quarantine Bureau, 361012 Xiamen (China); Chen Wengui [First Hospital of Xiamen, 361003 Xiamen (China); Lin Lin [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Song Xiuyu [First Hospital of Xiamen, 361003 Xiamen (China); Yan Xiaomei [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Hang Wei, E-mail: weihang@xmu.edu.cn [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Huang Benli [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China)

    2009-09-14

    Ultra performance liquid chromatography (UPLC) coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry has showed great potential in diabetes research. In this paper, a UPLC-oaTOF-MS system was employed to distinguish the global serum profiles of 8 diabetic nephropathy (DN) patients, 33 type 2 diabetes mellitus (T2DM) patients and 25 healthy volunteers, and tried to find potential biomarkers. The UPLC system produced information-rich chromatograms with typical measured peak widths of 4 s, generating peak capacities of 225 in 15 min. Furthermore, principal component analysis (PCA) was used for group differentiation and marker selection. As shown in the scores plot, the distinct clustering between the patients and controls was observed, and DN and T2DM patients were also separated into two individual groups. Several compounds were tentatively identified based on accurate mass, isotopic pattern and MS/MS information. In addition, significant changes in the serum level of leucine, dihydrosphingosine and phytoshpingosine were noted, indicating the perturbations of amino acid metabolism and phospholipid metabolism in diabetic diseases, which having implications in clinical diagnosis and treatment.

  4. Dysregulation of the Intrarenal Vitamin D Endocytic Pathway in a Nephropathy-Prone Mouse Model of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    John L. Fowlkes

    2011-01-01

    Full Text Available Microalbuminuria in humans with Type 1 diabetes (T1D is associated with increased urinary excretion of megalin, as well as many megalin ligands, including vitamin-D-binding protein (VDBP. We examined the DBA/2J diabetic mouse, nephropathy prone model, to determine if megalin and VDBP excretion coincide with the development of diabetic nephropathy. Megalin, VDBP, and 25-hydroxy-vitamin D (25-OHD were measured in urine, and genes involved in vitamin D metabolism were assessed in renal tissues from diabetic and control mice at 10, 15, and 18 weeks following the onset of diabetes. Megalin, VDBP, and 25-OHD were increased in the urine of diabetic mice. 1-α hydroxylase (CYP27B1 mRNA in the kidney was persistently increased in diabetic mice, as were several vitamin D-target genes. These studies show that intrarenal vitamin D handling is altered in the diabetic kidney, and they suggest that in T1D, urinary losses of VDBP may portend risk for intrarenal and extrarenal vitamin D deficiencies.

  5. Fast renal decline to end-stage renal disease: an unrecognized feature of nephropathy in diabetes.

    Science.gov (United States)

    Krolewski, Andrzej S; Skupien, Jan; Rossing, Peter; Warram, James H

    2017-06-01

    A new model of diabetic nephropathy in type 1 diabetes emerged from our studies of Joslin Clinic patients. The dominant feature is progressive renal decline, not albuminuria. This decline is a unidirectional process commencing while patients have normal renal function and, in the majority, progressing steadily (linearly) to end-stage renal disease (ESRD). While an individual's rate of renal decline is constant, the estimated glomerular filtration rate (eGFR) slope varies widely among individuals from -72 to -3.0 ml/min/year. Kidney Disease: Improving Global Outcomes guidelines define rapid progression as rate of eGFR declines > 5 ml/min/year, a value exceeded by 80% of patients in Joslin's type 1 diabetes ESRD cohort. The extraordinary range of slopes within the rapid progression category prompted us to partition it into "very fast," "fast" and "moderate" decline. We showed, for the first time, that very fast and fast decline from normal eGFR to ESRD within 2 to 10 years constitutes 50% of the Joslin cohort. In this review we present data about frequency of fast decliners in both diabetes types, survey some mechanisms underlying fast renal decline, discuss methods of identifying patients at risk and comment on the need for effective therapeutic interventions. Whether the initiating mechanism of fast renal decline affects glomerulus, tubule, interstitium or vasculature is unknown. Since no animal model mimics progressive renal decline, studies in humans are needed. Prospective studies searching for markers predictive of the rate of renal decline yield findings that may make detection of fast decliners feasible. Identifying such patients will be the foundation for developing effective individualized methods to prevent or delay onset of ESRD in diabetes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  6. Bamboo leaf extract ameliorates diabetic nephropathy through activating the AKT signaling pathway in rats.

    Science.gov (United States)

    Ying, Changjiang; Mao, Yizhen; Chen, Lei; Wang, Shanshan; Ling, Hongwei; Li, Wei; Zhou, Xiaoyan

    2017-12-01

    Diabetic nephropathy (DN) is one of the most severe diabetic complication and it is becoming become a worldwide epidemic, accounting for approximately one-third of all case of end-stage renal disease. However, the underlying mechanism and strategy to alleviate renal injury remain unclear. In the present study, we assessed the protective effect of bamboo leaf extract on the DN, and investigated the underlying mechanism by which bamboo leaf extract ameliorating DN. Diabetic rats were induced by 4 weeks high sugar and high fat diet, and then injected a single dose of STZ (35mg/kg) into abdominal cavity. Different dose of bamboo extract (50mg/kg, 100mg/kg and 200mg/kg) were orally administered every day for a period of 12 weeks. Body weight, blood glucose, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and 24-hour urinary protein (24 h-UP) were assessed. Total superoxide dismutase (T-SOD) activity and MDA (methane dicarboxylic aldehyde, MDA) level were tested by assay kit. Microstructural changes were observed by hematoxylin-eosin (HE) staining and electron microscopy. Expression of phosphorylated ser/thr protein kinase (P-AKT), phosphorylated glycogen synthase kinase-3 beta (P-GSK-3β), B cell lymphoma/leukemia 2-associated X protein (BAX) and cleaved-cysteinyl aspartate-specific proteinase-3 (Cleaved Caspase-3) were measured by Western-Blotting (WB). Results showed that diabetic rats had weight loss, high blood glucose, HbAlc, BUN, Scr and 24-UP and T-SOD activity were increased and MDA level was decreased in diabetic rats. Moreover, hyperglycemia could injury renal tissue ultrastructure, inhibit P-AKT level and increase P-GSK-3β, BAX and Cleaved Caspase-3 levels in rats. However, bamboo leaf extract treatment could reduce body weight loss, BUN, Scr, 24 h-UP and MDA level, improve T-SOD activity and alleviate renal injury in diabetic rats. Furthermore, bamboo leaf extract increased P-AKT level, decreased P-GSK-3β, BAX and

  7. Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress.

    Science.gov (United States)

    Liu, Tingting; Duan, Wang; Nizigiyimana, Paul; Gao, Lin; Liao, Zhouning; Xu, Boya; Liu, Lerong; Lei, Minxiang

    2018-02-05

    Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms. Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured. The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury. Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Wang, Zeng Si; Xiong, Fei; Xie, Xiao Hang; Chen, Dan; Pan, Jian Hua; Cheng, Li

    2015-03-31

    Diabetic nephropathy (DN) is a major cause of Chronic Kidney Disease and End-Stage Renal Disease throughout the world; however, the reversibility of diabetic nephropathy remains controversial. Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of DN. Astragaloside IV (AS-IV) is derived from Astragalus membranaceus (Fisch) Bge, a widely used traditional herbal medicine in China, and has diverse pharmacological activities including the attenuation of podocyte injury and amelioration of proteinuria in idiopathic nephrotic syndrome. The present study aimed to investigate the effect and mechanism of AS-IV on proteinuria in the rat streptozotocin (STZ)-induced model of diabetes. Male Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (Normal group), diabetic nephropathy (Model group), diabetic nephropathy plus AS-IV treatment (AS-IV group) and diabetic nephropathy plus 4-phenyl butyric acid treatment (PBA group). ER stress was induced in cultured human podocytes, pretreated with or without AS-IV, with tunicamycin (TM). At the end of 8 weeks, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour urinary protein excretion rate (UAER) were determined. Renal morphology was examined after periodic acid-Schiff staining of kidney sections. Apoptosis of podocytes was measured by flow cytometry. The total expression and phosphorylation of eIF2α, PERK and JNK, and the expression of CHOP and cleaved caspase-3 were determined by western blotting. The expression of glucose-regulated protein 78 (GRP78) and 150 kDa oxygen-regulated protein (ORP150) mRNA and protein was determined by real-time PCR and western blotting respectively. AS-IV treatment significantly reduced urinary albumin excretion, plasma creatinine and blood urea nitrogen levels, and prevented the mesangial matrix expansion and increase in mean mesangial induced by STZ. AS-IV also prevented the phosphorylation of eIF2α, PERK and JNK, and inhibited the

  9. Number and frequency of albuminuria measurements in clinical trials in diabetic nephropathy.

    Science.gov (United States)

    Kröpelin, Tobias F; de Zeeuw, Dick; Andress, Dennis L; Bijlsma, Maarten J; Persson, Frederik; Parving, Hans-Henrik; Heerspink, Hiddo J Lambers

    2015-03-06

    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 albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits. This study used data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes and macroalbuminuria. Albuminuria-lowering drug effects were estimated from one, two, or three urine collections at consecutive days before each study visit and reported as albuminuria change from baseline to end of treatment or the change over time considering an average of all follow-up albuminuria measurements. Increasing the number of urine collections for an albuminuria measurement at baseline and end of treatment or using all study visits during follow-up did not alter the average drug effect. The precision of the drug effect increased (decreased SEM) when the number of study visits and the number of 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. Increasing the number of urine collections per study visit and the number of visits over time does not change the average drug effect estimate but markedly increases the precision, thereby enhancing statistical power. Thus, clinical trial designs in diabetic

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

    Science.gov (United States)

    Kröpelin, Tobias F.; de Zeeuw, Dick; Andress, Dennis L.; Bijlsma, Maarten J.; Persson, Frederik; Parving, Hans-Henrik

    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 albuminuria shows a large day-to-day variability, this study assessed to what extent the average and the precision of the antialbuminuric drug effect varies with the number of urine collections at each visit and the number of follow-up visits. Design, setting, participants, & measurements This study used data from three randomized intervention trials (Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist Atrasentan) including patients with type 2 diabetes and macroalbuminuria. Albuminuria-lowering drug effects were estimated from one, two, or three urine collections at consecutive days before each study visit and reported as albuminuria change from baseline to end of treatment or the change over time considering an average of all follow-up albuminuria measurements. Results Increasing the number of urine collections for an albuminuria measurement at baseline and end of treatment or using all study visits during follow-up did not alter the average drug effect. The precision of the drug effect increased (decreased SEM) when the number of study visits and the number of 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. Conclusions Increasing the number of urine collections per study visit and the number of visits over time does not change the average drug effect estimate but markedly increases the

  11. Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan.

    Science.gov (United States)

    Chien, Hung-Yu; Chen, Chang-Yi; Chiu, Yen-Hui; Lin, Yi-Chun; Li, Wan-Chun

    2016-01-01

    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. 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 (ACRproteinuria (ACR>300mg/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. 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. Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.

  12. The effects of ozone therapy on caspase pathways, TNF-α, and HIF-1α in diabetic nephropathy.

    Science.gov (United States)

    Güçlü, Aydın; Erken, Haydar Ali; Erken, Gülten; Dodurga, Yavuz; Yay, Arzu; Özçoban, Özge; Şimşek, Hasan; Akçılar, Aydın; Koçak, Fatma Emel

    2016-03-01

    Accelerated apoptosis plays a vital role in the development of diabetic vascular complications. Ozone may attenuate diabetic nephropathy by means of decreased apoptosis-related genes. The aim of our study was to investigate the effect of ozone therapy on streptozotocin-induced diabetic nephropathy in rats. Also the histopathological changes in diabetic kidney tissue with ozone treatment were evaluated. The rats were randomly divided into six groups (n = 7): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). D, DI, and DOI groups were induced by a single intraperitoneal injection of streptozotocin. Ozone was given to the O, DO, and DOI groups. Group DI and DOI received subcutaneous (SC) insulin (3 IU). All animals received daily treatment for 6 weeks. Expressions of caspase-1-3-9, HIF-1α, and TNF-α genes were significantly higher in D group compared to C group (p Ozone treatment resulted in significant decrease in the expressions of these genes in diabetic kidney tissue compared to both C and D group (p ozone treatment to insulin therapy resulted in more significantly decrease in the expressions of these genes in diabetic tissue compared to only insulin-treated diabetic group (p ozone treatment resulted in decrease in the renal corpuscular inflammation and normal kidney morphology was observed. Both insulin and ozone therapies apparently improved kidney histological findings with less degenerated tubules and less inflammation of renal corpuscle compared to D, DO, and DI groups. Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.

  13. Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy

    OpenAIRE

    Sekhar, Pagadala Nataraj; Kishor, P. B. Kavi; P. K. Zubaidha; Hashmi, A. M; Kadam, T. A.; Anandareddy, Lakkireddy; De Maeyer, Marc; Kumar, K. Praveen; Bhaskar, B. Vijaya; Munichandrababu, T; Jayasree, G; Narayana, P. V. B. S; Gyananath, G

    2011-01-01

    The enzyme aldoreductase which plays an important role in pathogenesis of diabetic retinopathy, neuropathy, and nephropathy was purified from bovine lens, and its inhibitory activity was studied with the synthesized flavone derivatives 1-(2-hydroxyphenyl)ethanone as the starting material. Experimental study revealed that 2-chloroflavone shows less inhibitory activity of 60-70% than other flavones used in the study. To validate experimental results computationally, docking studies of new flavo...

  14. A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy

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    Jiao Ying Ou

    2016-01-01

    Full Text Available Objective. The purpose of this systematic review is to evaluate the evidence of Yiqi Yangyin Huoxue Method for diabetic nephropathy. Methods. 11 electronic databases, through September 2015, were searched to identify randomized controlled trials of Yiqi Yangyin Huoxue Method for diabetic nephropathy. The quality of the included trials was assessed using the Jadad scale. Results. 26 randomized controlled trials were included in our review. Of all the included trials, most of them were considered as high quality. The aggregated results suggested that Yiqi Yangyin Huoxue Method is beneficial to diabetic nephropathy in bringing down the microalbuminuria (SMD = −0.98, 95% CI −1.22 to −0.74, serum creatinine (SMD = −0.56, 95% CI −0.93 to −0.20, beta-2 microglobulin (MD = 0.06, 95% CI 0.01 to 0.12, fasting plasma glucose (MD = −0.35, 95% CI −0.62 to −0.08, and 2-hour postprandial blood glucose (MD = 1.13, 95% CI 0.07 to 2.20, but not in decreasing blood urea nitrogen (SMD = −0.72, 95% CI −1.47 to 0.02 or 2-hour postprandial blood glucose (SMD = −0.48, 95% CI −1.01 to 0.04. Conclusions. Yiqi Yangyin Huoxue Method should be a valid complementary and alternative therapy in the management of diabetic nephropathy, especially in improving UAER, serum creatinine, fasting blood glucose, and beta-2 microglobulin. However, more studies with long follow-up are warrant to confirm the current findings.

  15. Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated With the Development and Progression of Diabetic Nephropathy

    Science.gov (United States)

    Al-Kateb, Hussam; Boright, Andrew P.; Mirea, Lucia; Xie, Xinlei; Sutradhar, Rinku; Mowjoodi, Alireza; Bharaj, Bhupinder; Liu, Michelle; Bucksa, Jean M.; Arends, Valerie L.; Steffes, Michael W.; Cleary, Patricia A.; Sun, Wanjie; Lachin, John M.; Thorner, Paul S.; Ho, Michael; McKnight, Amy Jayne; Maxwell, A. Peter; Savage, David A.; Kidd, Kenneth K.; Kidd, Judith R.; Speed, William C.; Orchard, Trevor J.; Miller, Rachel G.; Sun, Lei; Bull, Shelley B.; Paterson, Andrew D.

    2008-01-01

    BACKGROUND Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS We observed association between rs17880135 in the 3′ region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64– 4.18], P = 5.6 × 10−5, q = 0.06) and persistent microalbuminuria (1.82 [1.29 –2.57], P = 6.4 × 10−4, q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10−3) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study. PMID:17914031

  16. Therapeutic Effect of Alprostadil in Diabetic Nephropathy: Possible Roles of Angiopoietin-2 and IL-18

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    Changqing Luo

    2014-08-01

    Full Text Available Background/Aims: To investigate the role of angiopoietin-2 (Ang-2 and IL-18 in the pathogenesis of diabetic nephropathy (DN and the molecular mechanisms through which alprostadil protects renal function. Methods: DN was induced by streptozotocin and intraperitoneal injection of alprostadil was given to diabetic mice. After 2, 4 and 8 weeks of alprostadil treatment, the mRNA and protein expression of kidney Ang-2 and IL-18 were detected by reverse transcription PCR, Western blot and immunohistochemistry analyses. Mouse glomerular endothelial cells (GEnCs were cultured in high glucose and treated with alprostadil. After transfection with an Ang-2-pcDNA and Ang-2-siRNA, both Ang-2 and IL-18 expression were measured by Western blot analyses. Results: Alprostadil treatment caused a significant decrease in the renal damage parameters. Both Ang-2 and IL-18 were significantly increased in DN mice and in GEnCs cultured in high glucose; however, their expression was greatly reduced by alprostadil treatment. Ang-2 could also increase IL-18 expression in cultured endothelial cells under high glucose, and this response was partially blocked by Ang-2 siRNA. Conclusions: Ang-2 and IL-18 may be associated with the development and progression of DN in mice. Alprostadil treatment can protect renal function by reducing proteinuria. These effects are mediated, at least in part, through down-regulation of Ang-2 and IL-18 expression.

  17. Serum amyloid A enrichment impairs the anti-inflammatory ability of HDL from diabetic nephropathy patients.

    Science.gov (United States)

    Mao, Jing Yan; Sun, Jia Teng; Yang, Ke; Shen, Wei Feng; Lu, Lin; Zhang, Rui Yan; Tong, Xuemei; Liu, Yan

    2017-10-01

    Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has been demonstrated in patients with type-2 diabetes mellitus (T2DM). However, whether HDL from patients with diabetic nephropathy (DN) suffers additional damage remains unknown. This study compared the anti-inflammatory capacities of HDL from healthy controls, T2DM patients with normal renal function, and T2DM patients with DN. HDL was isolated from healthy controls (n=33) and T2DM patients with normal renal function (n=21), chronic kidney disease (CKD) (n=27), and end-stage renal disease (ESRD) (n=27). Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers were pretreated with HDL (100μg/mL) for 1h, then incubated with lipopolysaccharide (LPS) (50ng/mL) for 24h. The anti-inflammatory ability of HDL was measured as the secretion of TNF-α in LPS-activated monocytes. The anti-inflammatory ability of HDL was gradually impaired as kidney function declined. Serum amyloid A (SAA) concentration in HDLDN significantly increased and was positively correlated with the impaired anti-inflammatory ability of HDL (Pearson r=0.315, P=0.006). Furthermore, HDL supplemented with SAA significantly increased TNF-α release from PBMCs compared with that from control HDL. These findings identified an impaired anti-inflammatory capacity of HDL from DN patients, which might be attributable to SAA enrichment. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Novel insights into the pathophysiology and clinical aspects of diabetic nephropathy.

    Science.gov (United States)

    Ilyas, Zubair; Chaiban, Joumana T; Krikorian, Armand

    2017-03-01

    Diabetic nephropathy (DN) is a well-described complication of diabetes mellitus and the leading cause of end stage renal disease (ESRD). Although increased albuminuria has been the gold standard for screening, data suggests that renal damage starts long before the onset of clinically apparent increases in macro and even micro-albuminuria. Clinical practice guidelines for the prevention of DN have been traditionally focused on the control of serum glucose, blood pressure and dyslipidemia, with some focus on the renin-angiotensin-aldosterone system (RAAS) as a main target for successful therapy. Recent evidence has led to a better understanding of the underlying mechanisms of the pathophysiology of this disease and suggests that various novels pathways can be targeted to delay and even prevent the progression of DN. Hence a more comprehensive therapeutic approach to therapy is on the horizon, carrying the promise for a more successful and impactful management. This review will highlight new insights into the pathophysiology, clinical aspects and future diagnostic and therapeutic modalities for DN.

  19. Epithelial-to-Mesenchymal Transition in Diabetic Nephropathy: Fact or Fiction?

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    Ivonne Loeffler

    2015-10-01

    Full Text Available The pathophysiology of diabetic nephropathy (DN, one of the most serious complications in diabetic patients and the leading cause of end-stage renal disease worldwide, is complex and not fully elucidated. A typical hallmark of DN is the excessive deposition of extracellular matrix (ECM proteins in the glomerulus and in the renal tubulointerstitium, eventually leading to glomerulosclerosis and interstitial fibrosis. Although it is obvious that myofibroblasts play a major role in the synthesis and secretion of ECM, the origin of myofibroblasts in DN remains the subject of controversial debates. A number of studies have focused on epithelial-to-mesenchymal transition (EMT as one source of matrix-generating fibroblasts in the diseased kidney. EMT is characterized by the acquisition of mesenchymal properties by epithelial cells, preferentially proximal tubular cells and podocytes. In this review we comprehensively review the literature and discuss arguments both for and against a function of EMT in renal fibrosis in DN. While the precise extent of the contribution to nephrotic fibrosis is certainly arduous to quantify, the picture that emerges from this extensive body of literature suggests EMT as a major source of myofibroblasts in DN.

  20. Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy

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    Ning Yan

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is one of the most common complications of diabetes mellitus (DM. However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT, and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1, and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.

  1. Role of Protein Kinase C (PKC in Podocytes and Development of Glomerular Damage in Diabetic Nephropathy

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    Beina eTeng

    2014-11-01

    Full Text Available The early glomerular changes in diabetes include a podocyte phenotype with loss of slit diaphragm proteins, changes in the actin cytoskeleton and foot process architecture. This review focusses on the role of the Protein Kinase C family in podocytes and points out the differential roles of classical, novel and atypical PKCs in podocytes. Some PKC-isoforms are indispensable for proper glomerular development and slit diaphragm maintenance whereas others might be harmful when activated in the diabetic milieu. Therefore some might be interesting treatment targets in the early phase of diabetes.

  2. Evaluation of the effectiveness of diabetic nephropathy stage III in patients with type 2 diabetes mellitus therapy with sulodexide

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    V. G. Kadzharyan

    2013-08-01

    Full Text Available Introduction. Diabetes mellitus (DM - takes the main place in the structure of endocrine diseases, and the third after cardiovascular and cancer pathology. In Ukraine 1.2 million of people suffer from diabetes and type 2 diabetes occurs in 85-90% of them. In 2004, 3.4 million of people died from diabetes complications. Diabetic nephropathy (DN is a serious chronic complication of diabetes that leads to the formation of nodular or diffuse glomerulosclerosis. It is the most frequent cause of terminal chronic renal failure (CRF in the world, accounting for over 25% of all cases of CRF. The generally accepted classification is Moggensen`s classification (1983, WHO, according to which five stages of diabetic nephropathy are identified, the first two stages of them are preclinical. Leading role in the pathogenesis of DN takes hyperglycemia, which is implemented by the phenomenon of glucosetoxicity. A lot of facts underscore the importance of inflammatory mechanisms triggered by cytokines. There's immune and non-immune theory of DN. The basis of non-immune theory is a violation of the synthesis of glycosaminoglycans (GAGs that are a major component of the glomerular basement membrane (GMB. GAGs create its negative charge, which prevents the passage through the renal filter small negatively charged molecules, including albumin. In hemodynamic regulation leading role belongs to the renin-angiotensin-aldosterone system (RAAS. The blockade of the RAAS system with ACE inhibitors is the basis of a treatment strategy of DN. All mentioned above became a reason for study of the possibility of a new direction in the treatment of DN using the drug sulodexid, which is a natural mixture of GAGs. Objective of the research. Evaluating the effectiveness of sulodexide therapy of DN stage III in patients with type 2 diabetes. Materials and methods. The patients were divided into 2 groups. Group I consisted of 24 patients aged 40 to 68 years. 5 of them were women and 19

  3. Effect of leflunomide combined with losartan potassium therapy on renal function and glomerular podocyte injury in patients with diabetic nephropathy

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    Xiu-Zhu Lin

    2017-04-01

    Full Text Available Objective: To study the effect of leflunomide combined with losartan potassium therapy on renal function and glomerular podocyte injury in patients with diabetic nephropathy. Methods: A total of 82 patients with diabetic nephropathy (CKDIIIa, IIIb stage who were treated in our hospital between June 2013 and May 2016 were selected as the research subjects, random number table was used to divide them into leflunomide (LEF group and control group who received leflunomide combined with losartan potassium therapy and losartan potassium monotherapy respectively. Before treatment and 8 weeks after treatment, serum contents of renal function indexes, RAAS molecules and inflammatory factors as well as urine contents of podocyte damage proteins were determined. Results: 8 weeks after treatment, serum Scr, BUN, CysC, PRA, AT-II, ALD, IL-1β, IL-6 and TNF-α contents, urine ACR levels as well as podocalyxin, nephrin, CA2AP and podocin contents of both groups of patients were significantly lower than those before treatment, and serum Scr, BUN, CysC, IL-1β, IL-6 and TNF-α contents, urine ACR level as well as podocalyxin, nephrin, CA2AP and podocin contents of LEF group were significantly lower than those of control group, serum PRA, ATII, ALD contents had no significant difference with control group. Conclusion: Leflunomide combined with losartan potassium therapy can improve the renal function of patients with diabetic nephropathy, and inhibit the inflammatory response injury to glomerular podocyte.

  4. Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti-fibrotic effects in streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Lu, Hung-Jen; Tzeng, Thing-Fong; Liou, Shorong-Shii; Da Lin, Sheng; Wu, Ming-Chang; Liu, I-Min

    2014-03-26

    Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN. Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0 mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. Ruscogenin administration did not lower the levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by ruscogenin. Ruscogenin treatment was found to markedly improve histological architecture in the diabetic kidney. Renal NF-κB activity, as wells as protein expression and infiltration of macrophages were increased in diabetic kidneys, accompanied by an increase in protein content of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in kidney tissues. All of the above abnormalities were reversed by ruscogenin treatment, which also decreased the expression of transforming growth factor-β1 and fibronectin in the

  5. Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy-a prospective follow--up study

    DEFF Research Database (Denmark)

    Astrup, A S; Tarnow, L; Christiansen, M

    2007-01-01

    AIM: Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohort...... of Type 1 diabetic patients. METHODS: In a prospective observational follow-up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0-10.3) years. PAPP-A was determined at baseline. RESULTS: In patients...... with diabetic nephropathy, plasma PAPP-A was elevated 3.6 (0.4-51.1) mIU/l [median (range)] vs. 2.1 (0.4-46.6) mIU/l in normoalbuminuric patients, P PAPP-A threshold of 10 mIU/l has been suggested. Thirty-seven patients were above the threshold and of these 13 patients...

  6. Dillenia indica L. attenuates diabetic nephropathy via inhibition of advanced glycation end products accumulation in STZ-nicotinamide induced diabetic rats.

    Science.gov (United States)

    Kaur, Navpreet; Kishore, Lalit; Singh, Randhir

    2018-01-01

    The present study was aimed to evaluate advanced glycation end products (AGEs) inhibitory activity of alcohol and hydro-alcohol extract (DAE and DHE) of Dillenia indica L. (Family: Dilleniaceae) and its potential in treatment of diabetic nephropathy by targeting markers of oxidative stress. D. indica was evaluated for its in vitro inhibitory activity against formation of AGEs by using bovine serum albumin. Diabetes was induced in male Wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. Diabetic rats were treated with different doses of extracts (100, 200 and 400 mg/kg) to analyze their nephroprotective effect. Tissue antioxidant enzymes level was measured along with the formation of AGEs in kidney to assess the effect of D. indica in ameliorating oxidative stress. D. indica showed significant inhibition of AGEs formation in vitro. D. indica produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, D. indica produced significant reduction in the formation of AGEs in kidneys. The present study concludes that D. indica as a possible therapeutic agent against diabetic nephropathy.

  7. Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Alkayyali, S; Lajer, M; Deshmukh, H

    2013-01-01

    Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2...... diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts. RESULTS: In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1...

  8. Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1 in diabetic nephropathy.

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    M Lucrecia Alvarez

    Full Text Available We previously observed association between variants in the plasmacytoma variant translocation 1 gene (PVT1 and end-stage renal disease (ESRD attributed to both type 1 and type 2 diabetes, and demonstrated PVT1 expression in a variety of renal cell types. While these findings suggest a role for PVT1 in the development of ESRD, potential mechanisms for involvement remain unknown. The goal of this study was to identify possible molecular mechanisms by which PVT1 may contribute to the development and progression of diabetic kidney disease. We knocked-down PVT1 expression in mesangial cells using RNA interference, and analyzed RNA and protein levels of fibronectin 1 (FN1, collagen, type IV, alpha 1 (COL4A1, transforming growth factor beta 1 (TGFB1 and plasminogen activator inhibitor-1 (SERPINE1 or PAI-1 by qPCR and ELISA, respectively. PVT1 expression was significantly upregulated by glucose treatment in human mesangial cells, as were levels of FN1, COL4A1, TGFB1, and PAI-1. Importantly, PVT1 knockdown significantly reduced mRNA and protein levels of the major ECM proteins, FN1 and COL4A1, and two key regulators of ECM proteins, TGFB1 and PAI-1. However, we observed a higher and more rapid reduction in levels of secreted FN1, COL4A1, and PAI-1 compared with TGFB1, suggesting that at least some of the PVT1 effects on ECM proteins may be independent of this cytokine. These results indicate that PVT1 may mediate the development and progression of diabetic nephropathy through mechanisms involving ECM accumulation.

  9. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    Science.gov (United States)

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives. Copyright © 2015. Published by Elsevier España, S.L.U.

  10. The estimated GFR, but not the stage of diabetic nephropathy graded by the urinary albumin excretion, is associated with the carotid intima-media thickness in patients with type 2 diabetes mellitus: a cross-sectional study

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    Ishida Hidenori

    2010-05-01

    Full Text Available Abstract Background To study the relationship between the intima-media thickness (IMT of the carotid artery and the stage of chronic kidney disease (CKD based on the estimated glomerular filtration rate (eGFR and diabetic nephropathy graded by the urinary albumin excretion (UAE in the patients with type 2 diabetes mellitus. Methods A cross-sectional study was performed in 338 patients with type 2 diabetes mellitus. The carotid IMT was measured using an ultrasonographic examination. Results The mean carotid IMT was 1.06 ± 0.27 mm, and 42% of the subjects showed IMT thickening (≥ 1.1 mm. Cerebrovascular disease and coronary heart disease were frequent in the patients with IMT thickening. The carotid IMT elevated significantly with the stage progression of CKD (0.87 ± 0.19 mm in stage 1, 1.02 ± 0.26 mm in stage 2, 1.11 ± 0.26 mm in stage 3, and 1.11 ± 0.27 mm in stage 4+5. However, the IMT was not significantly different among the various stages of diabetic nephropathy. The IMT was significantly greater in the diabetic patients with hypertension compared to those without hypertension. The IMT positively correlated with the age, the duration of diabetes mellitus, and the brachial-ankle pulse wave velocities (baPWV, and negatively correlated with the eGFR. In a stepwise multivariate regression analysis, the eGFR and the baPWV were independently associated with the carotid IMT. Conclusions Our study is the first report showing a relationship between the carotid IMT and the renal parameters including eGFR and the stages of diabetic nephropathy with a confirmed association between the IMT and diabetic macroangiopathy. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis and positive treatments for hypertension, dyslipidaemia, obesity, as well as hyperglycaemia are necessary when a reduced eGFR is found in diabetic patients.

  11. Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine E; Andersen, Steen; Zdunek, Dietmar

    2011-01-01

    of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary......Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels...

  12. [Using nested case-control study to appraise the effectiveness of Chinese medicines in the treatment of diabetic nephropathy].

    Science.gov (United States)

    Liu, Zhao-lan; Li, Qing; Mu, Yu-jie; Gao, Ying; Liu, Jian-ping

    2012-09-01

    A nested case-control study was carried out to assess the effectiveness of Chinese medicines in the treatment of diabetic nephropathy, so as to explore the feasibility of using nested case-control study on effect assessment of Chinese medicine. Nested case-control study was applied and the participants were enrolled from the subjects recruited in a cohort study. The cases and the controls were matched by 1 to 4 in age, gender, nationality and the stage of diabetic nephropathy when recruited in the cohort study. The EpiData 3.1 software was used for inputting data and SAS system was used for data analysis. Conditional logistic regress was applied to analyze the relationship between treatment and the progression of diabetic nephropathy. The study power was estimated and the sample sizes for case-control study and cohort study were recalculated based on the data from the cohort study. Eight cases and 32 controls were recruited in this study. The education level, ratio of drug withdrawal, change of therapy, syndrome differentiation and treatment were not significantly different in case and control groups. The progression of diabetic nephropathy was not significantly related with the treatment and the odds ratio (OR) value was 0.725 with a 95% confidence interval from 0.174 to 3.030. The statistical power of the study was 5%. To achieve the statistical power of 80%, 1 350 (270:1 080) participants were needed for 1:4 matched case-control study, 880 (440:440) for 1:1 paired case-control study, and 1 020 (510:510) for 1:1 control study. The treatment method is not significantly related with the progress of diabetic nephropathy. The nested case-control study is applicable in the therapeutic effect evaluation of Chinese medicine. Basic studies such as cross-sectional studies should be carried out to supply fundamental information for other types of studies including case-control study, cohort study and randomized clinical trials. Large sample size studies were needed to

  13. Kidney Function Improvement by Soy Milk Containing Lactobacillus plantarum A7 in Type 2 Diabetic Patients With Nephropathy: a Double-Blinded Randomized Controlled Trial.

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    Abbasi, Behnood; Ghiasvand, Reza; Mirlohi, Maryam

    2017-01-01

    Even with the ultimate medical management, more than one-third of diabetic patients develop diabetic nephropathy. To our knowledge, there is no study that has examined the effect of probiotic soy milk on kidney function in type 2 diabetic patients with nephropathy. This clinical trial aimed to assess the effects of consumption of probiotic soy milk, compared with conventional soy milk, on kidney-related indexes in patients with diabetic nephropathy. In a randomized double-blinded placebo-controlled trial, 44 patients were randomly assigned to receive 200 mL/d of either soy milk containing Lactobacillus plantarum A7 or conventional soy milk for 8 weeks. Primary endpoints included urinary albumin excretion, estimated glomerular filtration rate, interlukin-18, serum sialic acid, and serum creatinine. Fasting blood samples and morning fasting spot urine samples were collected at the beginning and after 8 weeks for evaluation of biochemical parameters. Forty patients completed the study. Administration of probiotic soymilk resulted in a significant reduction in albuminuria (P = .03), serum creatinine (P soy milk. Probiotic soymilk supplementation also led to a significant improvement in estimated glomerular filtration rate (15.9 ± 10.8 mL/min versus 3.2 ± 8.4 mL/min, P soy milk was safe and well-tolerated by patients with diabetic nephropathy for 8 weeks. Probiotic soy milk also improved indexes of kidney function in type 2 diabetic patients with nephropathy.

  14. Association of Postbreakfast Triglyceride and Visit-to-Visit Annual Variation of Fasting Plasma Glucose with Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes

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    Kaori Kitaoka

    2016-01-01

    Full Text Available Urinary albumin/creatinine ratio (ACR was measured at baseline and after a median follow-up of 6.0 years in 161 patients with type 2 diabetes. Intrapersonal means and SD of HbA1c, systolic BP, fasting, and postmeal plasma glucose (FPG and PMPG, resp. and serum triglycerides (FTG and PMTG, resp. were calculated in each patient during the first 12 months after enrollment. Associations of these variables with nephropathy progression (15 patients with progression of albuminuric stages and 5 with ACR doubling within the microalbuminuric range were determined by multivariate logistic regression analysis providing odds ratio with 95% confidential interval. Patients with nephropathy progression, compared with those without nephropathy progression, had higher HbA1c (p<0.01. They also had higher means and SD of FPG (both p<0.05, FTG (both p<0.05, and PMTG (p=0.001. Multivariate logistic regression analysis demonstrated that SD-FPG (1.036, 1.001–1.073, p=0.04 and PMTG (1.013, 1.008–1.040, p=0.001 were significant predictors of progression of nephropathy even after adjustment for mean FPG and SD-FTG, age, sex, BMI, waist circumference, diabetes duration and therapy, means and SDs of HbA1c, PPG, FTG and systolic BP, baseline ACR, smoking status, and uses of antihypertensive and lipid-lowering medications. Consistency of glycemic control and management of postmeal TG may be important to prevent nephropathy progression in type 2 diabetic patients.

  15. Diabetic Retinopathy and Clinical Parameters Favoring the Presence of Diabetic Nephropathy could Predict Renal Outcome in Patients with Diabetic Kidney Disease.

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    Hung, Chi-Chih; Lin, Hugo You-Hsien; Hwang, Daw-Yang; Kuo, I-Ching; Chiu, Yi-Wen; Lim, Lee-Moay; Hwang, Shang-Jyh; Chen, Hung-Chun

    2017-04-21

    Diabetes duration, diabetic retinopathy (DR), and a diagnostic model have been proposed as clinical parameters favoring the presence of diabetic nephropathy (DN) in biopsied patients with diabetic kidney disease. DN, compared with non-diabetic renal disease, had poorer renal outcomes. We tested whether these clinical parameters favoring DN are associated with poorer renal outcomes in non-biopsied patients. In this study, 1330 patients with type 2 diabetes and chronic kidney disease stages 1-4 were included and divided according to diabetes mellitus (DM) duration >8 years, DR, or a diagnostic model for DN. These clinical parameters favoring DN were found in 62-77% of patients and associated with higher levels of proteinuria. In a Cox survival analysis, DR and the diagnostic model favoring DN were associated with an increased risk for end-stage renal disease with adjusted hazard ratios of 1.69 (95% CI: 1.16-2.45, P = 0.006) and 1.66 (95% CI: 1.05-2.61, P = 0.029), respectively. DR was associated with an increased risk for rapid renal disease progression. DM >8 years was not associated with renal outcome. Propensity score-matched analyses also showed similar results. In conclusion, DR and the diagnostic model favoring DN were associated with poorer renal outcomes.

  16. Early onset type 2 diabetes

    DEFF Research Database (Denmark)

    Bo, A; Thomsen, R W; Nielsen, J S

    2017-01-01

    was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

  17. Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus.

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    Zhou, Tian-Biao; Drummen, Gregor P C; Jiang, Zong-Pei; Li, Hong-Yan

    2015-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C → T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case-control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies.

  18. The Missing Link - Likely Pathogenetic Role of GM3 and Other Gangliosides in the Development of Diabetic Nephropathy

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    Igor Vukovic

    2015-05-01

    Full Text Available Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy.

  19. Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

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    Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

    2017-06-01

    To determine whether ACE2 I/D and BDKRB23 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R4+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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    Keisuke Ishizawa

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

  1. Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy

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    Gareth J. McKay

    2016-01-01

    Full Text Available Objective. WNT/β-catenin pathway members have been implicated in interstitial fibrosis and glomerular sclerosis disease processes characteristic of diabetic nephropathy (DN, processes partly controlled by transcription factors (TFs that bind to gene promoter regions attenuating regulation. We sought to identify predicted cis-acting transcription factor binding sites (TFBSs overrepresented within WNT pathway members. Methods. We assessed 62 TFBS motif frequencies from the JASPAR databases in 65 WNT pathway genes. P values were estimated on the hypergeometric distribution for each TF. Gene expression profiles of enriched motifs were examined in DN-related datasets to assess clinical significance. Results. Transcription factor AP-2 alpha (TFAP2A, myeloid zinc finger 1 (MZF1, and specificity protein 1 (SP1 were significantly enriched within WNT pathway genes (P values < 6.83 × 10−29, 1.34 × 10−11, and 3.01 × 10−6, resp.. MZF1 expression was significantly increased in DN in a whole kidney dataset (fold change = 1.16; 16% increase; P=0.03. TFAP2A expression was decreased in an independent dataset (fold change = −1.02; P=0.03. No differential expression of SP1 was detected. Conclusions. Three TFBS profiles are significantly enriched within WNT pathway genes highlighting the potential of in silico analyses for identification of pathway regulators. Modification of TF binding may possibly limit DN progression, offering potential therapeutic benefit.

  2. Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice.

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    Rossi, Claudia; Marzano, Valeria; Consalvo, Ada; Zucchelli, Mirco; Levi Mortera, Stefano; Casagrande, Viviana; Mavilio, Maria; Sacchetta, Paolo; Federici, Massimo; Menghini, Rossella; Urbani, Andrea; Ciavardelli, Domenico

    2017-11-13

    The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries. In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia. Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids β-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment. Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN.

  3. Attenuation of diabetic nephropathy by Sanziguben Granule inhibiting EMT through Nrf2-mediated anti-oxidative effects in streptozotocin (STZ)-induced diabetic rats.

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    Zhang, Chenxue; Li, Qian; Lai, Sisi; Yang, Lei; Shi, Guoqi; Wang, Qing; Luo, Zijie; Zhao, Ruizhi; Yu, Yang

    2017-06-09

    Diabetic nephropathy (DN) is an acute and serious diabetic complication characterized by renal hypertrophy and renal fibrosis with the expansion of extracellular matrices. Diabetic nephropathy has become a major cause of end-stage kidney disease. Sanziguben Granule (SZGB) is a compound prescription which has been widely applied in clinical medicine for the prevention and treatment of diabetic nephropathy as well as for acute and chronic kidney injuries. However, the mechanism of protective effects of SZGB in DN remains unclear. In this research, we investigated the effects of SZGB on renal interstitial fibrosis, antioxidant proficiency, and apoptosis in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by performing a right uninephrectomy along with a single intraperitoneal injection of STZ. Rats were divided into six groups including sham, DN, SZGB-D, SZGB-Z, SZGB-G and fosinopril. SZGB and fosinopril were given to rats by gavage for 12 weeks. Samples from urine, blood and kidneys were collected for biochemical, histological, immunohistochemical and western blot analyses. We found that rats treated with SZGB showed reduced 24-h urinary protein excretion along with reduced serum total cholesterol (TC) and triglyceride (TG) levels. SZGB was also shown to prevent the disruption of catalase activity and reduce serum urea, creatinine, and renal malondialdehyde while increasing glutathione levels. Moreover, SZGB administration markedly improved the expression levels of E-cadherin, 4-HNE, Nrf2, HO-1, and Bcl-2, while it decreased the expression levels of Vimentin, α-SMA and Cleaved caspase-3 in the kidneys of diabetic rats. The renoprotective effects of SZGB was believed to be mediated by its antioxidant capacity, and SZGB treatment attenuated renal fibrosis through stimulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Therefore, it is suggested that SZGB can restrain epithelial

  4. Screening of diabetic nephropathy patients prone to triggering factors of diabetic foot

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    Regina Coeli Vasques de Miranda Burneiko

    2010-06-01

    Full Text Available Objective: To survey the prevalence of diabetic paients in the hemodialysis unit, screening those prone to outbreak of neuropathy and signs and symptoms of diabetic foot. Methods: We conducted a survey of the number of diabetics in a hemodialysis unit to apply the Michigan Neuropathy Screening Instrument Questionnaire in order to screen subjects with signs of sensory loss. Also, we observed variables related to the magnitude of the disease. The subjects were divided into two groups: Group A, no sensory deficit with a score of less than five and Group B with sensitive deficit with a score greater than or equal to six. Group B was submitted to examination, muscle strength testing, nerve palpation, and sensitivity testing of the feet. We applied the Mann-Whitney test to verify differences between groups (p <0.05. Results: Of the 168 participants of dialysis, 37 (22.02% were diabetic and of these 34 (20.24% joined in the study. To characterize the group B (n = 20, we did a frequency distribution and 4 (20% presented alterations related to nerve palpation, 11 (55% regarding muscle strength, 17 (85% to sensitivity testing, 11 (55% had neuropathy, 6 (30% had plantar ulcers, 4 (20% amputations and 100% were unaware of the diabetic foot syndrome. Conclusions: There was considerable percentage of diabetics in the hemodialysis unit, and more than half of them showed signs of neuropathy, decreased muscle strength and at least one of the signs and symptoms of diabetic foot.

  5. [Albuminuria in the diabetic patient: practical management].

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    Kistler, Andreas D

    2013-10-02

    Diabetic Nephropathy is the most common cause of end stage renal disease in Western countries. An increased urinary albumin excretion represents a characteristic sign of diabetic kidney damage. Regular screening for microalbuminuria allows early detection and timely intervention. In overt diabetic nephropathy, quantification of albuminuria helps monitoring disease progression. Therapeutic interventions to reduce albuminuria retard progression of nephropathy and reduce cardiovacular mortality, since albuminuria represents an independent cardiovascular risk factor. This review article describes the natural history of diabetic nephropathy and discusses practical issues for the measurement of albuminuria. Available prophylactic and therapeutic measures, particularly glycemic control and inhibition of the renin-angiotensin-aldosteron system, are reviewed using an evidence based approach.