Therapies For Diabetic Kidney Disease Research Articles

Current developments in renal failure in diabetic patients

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease. Recent studies demonstrate that in a significant part of diabetic patients the renal insufficiency is frequently caused by non-diabetic kidney diseases, so that an effective clarification of untypical clinical courses is mandatory. Important cornerstones of DKD therapy are an optimized glycaemic management as well as a good blood pressure control. Although the prognosis of DKD has been improved in the last years, it is, even with novel therapy approaches, not possible to prevent the development of DKD. It remains to hope that with extended knowledge, intensified preclinical studies and well-defined clinical trials novel nephroprotective therapies become available in the next years.

Glomerular endothelial cell injury and cross talk in diabetic kidney disease.

Diabetic kidney disease (DKD) remains a leading cause of new-onset end-stage renal disease (ESRD), and yet, at present, the treatment is still very limited. A better understanding of the pathogenesis of DKD is therefore necessary to develop more effective therapies. Increasing evidence suggests that glomerular endothelial cell (GEC) injury plays a major role in the development and progression of DKD. Alteration of the glomerular endothelial cell surface layer, including its major component, glycocalyx, is a leading cause of microalbuminuria observed in early DKD. Many studies suggest a presence of cross talk between glomerular cells, such as between GEC and mesangial cells or GEC and podocytes. PDGFB/PDGFRβ is a major mediator for GEC and mesangial cell cross talk, while vascular endothelial growth factor (VEGF), angiopoietins, and endothelin-1 are the major mediators for GEC and podocyte communication. In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle. Therefore, GEC injury may predispose to albuminuria in diabetes either directly or indirectly by communication with neighboring podocytes and mesangial cells via secreted mediators. Identification of novel mediators of glomerular cell cross talk, such as microRNAs, will lead to a better understanding of the pathogenesis of DKD. Targeting these mediators may be a novel approach to develop more effective therapy for DKD.

Nitro-oleic acid is a novel anti-oxidative therapy for diabetic kidney disease

diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) in the United states ([4][1]). While the number of persons developing ESRD continues to increase annually, those who have diabetes listed as a primary cause of ESRD have stayed constant while the incidence of

Management of diabetic kidney disease: Recent advances

Diabetic kidney disease, in present days, is being recognized as the commonest cause of end stage renal disease. Though there is no absolute therapy for diabetic kidney disease, decades of hard work has recognized some modifiable factors that can prevent its progression. This article is an attempt to review some recent advances in the understanding, diagnosis and management of diabetic kidney disease

Getting a Notch Closer to Understanding Diabetic Kidney Disease

Diabetic kidney disease (DKD) is one of the most devastating complications of diabetes. Renal dysfunction develops in about one-third of patients with diabetes (1). Diabetic nephropathy is characterized by albuminuria, glomerulosclerosis, and progressive loss of renal function. Current therapies for DKD, including blood glucose control, angiotensin II receptors blockers, and ACE inhibitors, slow down, but do not halt, the progression to end-stage renal disease after overt nephropathy has been established (2). Recent studies indicate that podocyte injury and depletion play key roles in the pathogenesis of DKD (3,4). Clinical observational studies showed a strong correlation between podocyte density, albuminuria and renal function decline in patients with type 1 and type 2 diabetes (5). Notch signaling regulates many aspects of metazoan development and tissue renewal (6). Notch is a transmembrane protein that interacts with ligands of the Jagged and Delta family (7). In mammals, there are four Notch receptors (Notch 1–4), two Jaggeds, and three delta-like ligands (8). Each of these proteins show a cell type- and tissue-specific expression. Notch is made in the endoplasmic reticulum as pre-Notch. A furin-like convertase cleaves pre-Notch to intracellular and extracellular domain. The protein is then transported to the plasma membrane. Interaction of the ligand with the Notch receptor triggers a series of proteolytic cleavage, by ADAM, a disintegrin and metalloprotease and by the γ-secretase complex. The final cleavage releases the Notch intracellular domain (NICD), which then moves to the nucleus, where it can regulate gene …

Abstract 5264: Recombinant Human Angiotensin Converting Enzyme 2 Normalizes Blood Pressure and Reduces the Progression of Diabetic Nephropathy

Background: Diabetes nephropathy is one of the most common causes of end-stage renal failure. Inhibition of ACE2 function exacerbates diabetic kidney injury while renal ACE2 is downregulated in diabetic nephropathy. We hypothesize that recombinant human ACE2 (rhACE2) will slow the progression of diabetic kidney injury. Methods and Results: Male 12-week old diabetic Akita mice ( Ins2 WT/C96Y ) and controls ( Ins2 WT/WT ) were injected daily with rhACE2 (2 mg/kg, i.p.) or placebo for four consecutive weeks. In Akita Ins2 WT/C96Y mice injected with hrACE2, plasma ACE2 activity showed a marked increase resulting in significant reduction in urinary albumin excretion (118±21 vs 224±16 μ g/24 hrs; n=6~8; p<0.05). Treatment with rhACE2 decreased renal cortical angiotensin (Ang) II (12.1±1.9 vs 22.4±3.2 pg/mg; p<0.05) and increased Ang (1–7) (14.2±2.1 vs 8.8±1.9 pg/mg; p<0.05) levels, respectively, independent of changes in the expression of Ace and Ace2 while NADPH oxidase activity in renal cortical tissue from Akita mice was reduced by treatment with rhACE2 (364±45 vs 1720±277 RLU/sec/mg protein; n=6, p<0.05). These effects resulted in normalization of the increased extracellular matrix gene expression ( α -smooth muscle actin, collagen III and fibronectin), reduction in glomerular volume and basement membrane thickness in the diabetic Akita mice. Activation of protein kinase C (PKC)á and PKCâ was reduced by 60 –70% in Akita diabetic mice treated with rhACE2. Ang II and high glucose-induced reactive oxygen species generation was evaluated using lucigenin-based NADPH oxidase activity and DHE fluorescence in cultured rat mesangial cells was suppressed by 25 and 250 ng/ml of rhACE2 in a dose-dependent manner. The mild hypertension in Akita Ins2 WT/C96Y mice was normalized by treatment with rhACE2 (122.3±2.1 vs 108.4±1.9 mmHg; n=6, p<0.05) while the beneficial effects seen with rhACE2 occurred in the absence of hyperkalemia or acute renal failure and without a differential impact on hyperglycemia in the Akita diabetic model. Conclusions: We conclude that biologic antagonism of the RAS using rhACE2 can slow the progression of diabetic kidney injury and ACE2 may prove to be a useful adjunctive therapy for diabetic kidney disease.

Patient-derived Stem Cell Therapy for Diabetic Kidney Disease

Patient-derived Stem Cell Therapy for Diabetic Kidney Disease