Reversal of Lesions of Diabetic Nephropathy After Pancreas Transplantation

Fioretto, Paola; Steffes, Michael W.; Sutherland, David E.R.; Goetz, Frederick C.; Mauer, Michael

doi:10.1016/s0022-5347(01)61860-3

Cited by 170 publications

(232 citation statements)

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“…These findings lend support to the notion that chronic HBV infection might adversely affect the metabolic milieu of subjects who are at risk of developing type 2 diabetes. Given the importance of glycaemia as one of the key determinants of progression of albuminuria and development of ESRD [24,25], it is plausible that chronic HBV infection might worsen insulin resistance and hyperglycaemia, which interact with chronic inflammation to increase the risk of ESRD in our patients. In support of our hypothesis, HBsAg was found to be an independent risk factor for ESRD along with albuminuria, eGFR, diastolic blood pressure and anaemia.…”

Section: Discussionmentioning

confidence: 99%

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

et al. 2006

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Aims/hypothesis: We examined the association between chronic hepatitis B virus (HBV) infection and clinical outcomes in a consecutive cohort of Chinese patients with type 2 diabetes. Subjects, materials and methods: Between 1995 and 1999, 2,838 type 2 diabetes patients underwent comprehensive assessments and blood screening for hepatitis B surface antigen (HBsAg). The risk of occurrence of cardiovascular events and end-stage renal disease (defined as need for dialysis, doubling of serum creatinine or serum creatinine ≥500 μmol/l) was compared between HBsAg-positive and HBsAg-negative groups. Results: At baseline, HBV-infected patients (n=286, 10.1%) were younger (51.0±11.5 vs 53.7±12.7 years, p=0.004), had earlier onset of diabetes (51.0±11.5 vs 53.7±12.7 years, p=0.001) and a higher frequency of retinopathy (28 vs 22%, p=0.03) than non-HBV-infected patients. After a median follow-up of 3.5 years (interquartile range: 1.7-5.9 years) and adjustment of age, glycaemic control and other potential confounding factors, HBV-infected patients were more likely to develop end-stage renal disease than non-HBV infected patients (8.7 vs 6.4%) with a hazard ratio of 4.5 (95% CI 1.1-18.6). The difference in the frequency of cardiovascular endpoints was not statistically significant. Conclusions: In Chinese type 2 diabetes patients, chronic HBV infection was associated with increased risk of end-stage renal disease, and this was independent of other potential confounding factors. Early identification of HBV status and close surveillance of renal function are important in patients with type 2 diabetes who are living in areas where HBV is endemic or who are at risk of chronic HBV infection.

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Section: Discussionmentioning

confidence: 99%

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

et al. 2006

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“…Hyperglycaemia is a necessary precondition for the development of diabetic renal lesions [4,5], while systemic hypertension is an equally important aggravating factor of the disease [6]. Mechanisms including glomerular hypertension with hyperfiltration, renin-angiotensin system (RAS) activation, increased oxidative stress and advanced glycation end-products, activation of the protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) pathways, growth factors and cytokines such as TGF-β, and genetic susceptibility have been identified as important deteriorating factors [2,7,8], but the precise mechanisms involved in the progression of diabetic renal injury remain elusive.…”

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confidence: 99%

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

et al. 2006

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Aims/hypothesis Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. Materials and methods We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. Results After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-β and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. Conclusions/interpretation Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

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“…26,27 Pancreatic transplantation to achieve normal glycemic control has yielded promising results; reduction in proteinuria 28 and histologic improvements in diabetic glomerulopathy. [29][30][31] In summary, intensive glycemic treatment in both DMT1 and DMT2 reduces the risk and progression of early DN. The specific goal for HbA1c should be individualized considering the potential benefits and harms of different levels of HbA1c.…”

Section: Intensive Glucose Controlmentioning

confidence: 99%

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

et al. 2011

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Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, proteinuria/albuminuria reduction, interruption of the renin-angiotensin-aldosterone system through the use of angiotensin converting enzyme inhibitors and angiotensin type-1 receptor blockers, along with dietary modification and cholesterol lowering agents. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are urgently needed. This review highlights the available standard therapeutic approaches to manage progressive diabetic nephropathy, including markers for early diagnosis of diabetic nephropathy. Furthermore, we will discuss emerging strategies such as PPAR-gamma agonists, Endothelin blockers, vitamin D activation and inflammation modulation. Finally, we will summarize the recommendations of these interventions for the primary care practitioner.

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Reversal of Lesions of Diabetic Nephropathy After Pancreas Transplantation

Cited by 170 publications

References 0 publications

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

Chronic hepatitis B viral infection independently predicts renal outcome in type 2 diabetic patients

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

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