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

BACKGROUND/AIMS: The aim of this post-hoc analysis of a prospective study in patients with type 2 diabetic nephropathy was to investigate whether treatment with the angiotensin II type 1 receptor blocker irbesartan leads to a reduction in the serum levels of the advanced glycation end products (AGEs) pentosidine and N(epsilon)-carboxymethyllysine ...

PURPOSE OF REVIEW: To discuss mouse models of diabetic nephropathy and their use in discovering genetic risk factors predisposing to diabetic nephropathy. RECENT FINDINGS: Despite occurring in only 10-40% of diabetic patients, diabetic nephropathy is the largest single cause of end stage renal disease in the USA. Accumulated evidence points ...

In the past, hyperfiltration and increased glomerular capillary pressure have been identified as important determinants of the development of DN (diabetic nephropathy). Recently, some basic research and clinical reviews on DN have omitted identifying hyperfiltration as an important risk factor. At the same time, different rodent models of DN have ...

The protein kinase C (PKC) family consists of 13 members categorized as conventional or novel depending on whether diacylglycerol, calcium, or phosphatidylserine is required for activation. High glucose leads to activation of different forms of PKC across tissue types, thus determining the kind of diabetes-induced organ damage. PKC beta was ...

Nephropathy is one of the most common and severe complications of diabetes mellitus. The mechanism of diabetic nephropathy, however, remains incompletely understood. To elucidate the mechanism of diabetic nephropathy, we focus on the role of a vitamin K-dependent growth factor, growth arrest-specific gene 6 (Gas6), and its receptor Axl in ...

AIM: The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-beta-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. SUBJECTS AND METHODS: PC-1, APN, ...

BACKGROUND: Cyclo-oxygenase (COX)-2 inhibitors were introduced to world markets with claims of improved gastrointestinal safety compared with traditional NSAIDs. Randomized clinical trials had demonstrated fewer adverse gastrointestinal events with COX-2 inhibitors, but no difference with other adverse events, including adverse renal events. There was a rapid uptake of these medicines. ...

BACKGROUND/AIMS: Advanced glycation end products (AGEs) are involved in diabetic nephropathy. The AGE inhibitor pyridoxamine (PM) is renoprotective in experimental chronic allograft nephropathy supporting its potential in non-diabetic renal damage. METHODS: We studied the effects of PM in adriamycin nephropathy (AN; 1.5 mg/kg i.v.). Six weeks after disease induction, treatment ...

PURPOSE OF REVIEW: Podocyte injury plays a key role in the development of diabetic nephropathy. This review discusses recent advances in our understanding of mechanisms of podocyte injury in diabetes mellitus and the associated alterations in the function of the glomerular filtration barrier. RECENT FINDINGS: The effects of hyperglycemia on ...

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 ...

Diabetic nephropathy is the most common cause of end-stage renal disease in the world, and accounts for a significant increase in morbidity and mortality in patients with diabetes. Therapeutic options such as strict blood pressure and/or glycemic control are effective for preventing the development and progression of diabetic nephropathy, but ...

Diabetic nephropathy is characterized by excessive amassing of extracellular matrix (ECM) with thickening of glomerular and tubular basement membranes and increased amount of mesangial matrix, which ultimately progress to glomerulosclerosis and tubulo-interstitial fibrosis. In view of this outcome, it would mean that all the kidney cellular elements, i.e., glomerular endothelia, ...

Diabetic nephropathy is the single most common cause of end-stage renal disease (ESRD) and accounts for significant morbidity and mortality. While the incidence of ESRD increased dramatically in the 1980s and 1990s, the U.S. Renal Data System (USRDS) 2005 Annual Data Report shows that 338 out of every million Americans ...

Diabetes mellitus is recognized as a leading cause of chronic kidney disease and end-stage renal failure. Chronic renal failure is associated with insulin resistance and, in advanced renal failure, decreased insulin degradation. Both of these abnormalities are partially reversed with the institution of dialysis. Except for diet with protein restriction, ...

Diabetic nephropathy is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Chemokines are important participators in the recruitment of specific subpopulations of inflammatory cells into renal compartments. MCP-1/CCL2 has been identified as having a key role in monocyte/macrophage recruitment in animal models ...

AIM: The objective of this study is to correlate microalbumin and sialic acid levels with anthropometric variables in type 2 diabetic patients with and without nephropathy. METHODS: This study was a case control study and included 108 Trinidadian subjects (aged 15-60 years) of which 30 were healthy individuals, 38 had ...

AIM: The rheological properties of erythrocytes are impaired in diabetes mellitus, especially because of changes in their membrane lipid composition.The aim of this study was to determine and examine the relationship between red blood cell (RBC) membrane and serum lipid composition in type II diabetes subjects with and without nephropathy. ...

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 ...

AIMS/HYPOTHESIS: ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5'diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a ...

Across all ages, the incidence and rate of progression of most nondiabetic renal diseases are markedly higher in men compared with age-matched women. These observations suggest that female sex may be renoprotective. In the setting of diabetes, however, this female protection against the development and progression of renal disease is ...

Pyridoxamine (PM) is a promising drug candidate for treatment of diabetic nephropathy. The therapeutic effect of PM has been demonstrated in multiple animal models of diabetes and in phase II clinical trials. However, the mechanism of PM therapeutic action is poorly understood. One potential mechanism is scavenging of pathogenic reactive ...

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 performed a prospective observational follow-up study including 397 type 1 diabetic patients with ...

BACKGROUND: Renal diseases in diabetes include diabetic nephropathies (DN) and non-diabetic renal diseases (NDRD). The clinical differentiation between these two categories is usually not so clear and effective. This study aims to develop a quantified differential diagnostic model. METHODS: We consecutively screened the diabetic patients with overt proteinuria but no ...

BACKGROUND: Changes of renal nitric oxide (NO) production have been associated with glomerular hyperfiltration, vascular permeability, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. Several studies demonstrated an up- as well as downregulated expression of NO-synthases (NOS) in experimental diabetic nephropathy. It is still not yet specified whether the regulation and activity of ...

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 with different modifications is differentially reduced in the GBM and ...

Recently, circulating soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) was introduced as a potential biomarker which is downregulated in atherosclerosis. In the current study, we hypothesized that sTWEAK serum levels are decreased in end-stage renal disease and in patients with type 2 diabetes mellitus (T2DM) since both conditions ...

Although diabetic nephropathy occurs in only a minority of patients with diabetes, it is the major cause of end-stage renal disease in the United States. Hyperglycemia and hypertension are important factors predisposing patients to diabetic nephropathy, but accumulating evidence points to critical genetic factors predisposing only a subset of patients ...

Contrast-induced nephropathy (CIN) continues to be a significant complication of the increasing use of iodinated contrast media. There have been few new insights into pathogenesis; despite multiple strategies aimed at prophylaxis, very few have proven efficacious. This article reviews our current knowledge regarding CIN, with emphasis on patients with diabetes.

Diabetic nephropathy is the leading cause of end-stage renal disease. Novel preventive measures for diabetic renal complications are urgently needed. Miyazaki et al. report that rosiglitazone, a thiazolidinedione insulin sensitizer and a potent peroxisome proliferator-activated receptor gamma agonist, not only effectively improves glycemic control but also halts progression of albuminuria ...

As is diabetes itself, diabetic angiopathy is a multi-factorial disease. Advanced glycation endproducts (AGE) cause vascular cell derangement characteristic of diabetes, and this is mainly mediated by their interaction with receptor for AGE (RAGE). When made diabetic, RAGE-overexpressing transgenic mice exhibited exacerbation of the indices of nephropathy, and this was ...

OBJECTIVE: The purpose of this study was to examine whether known genetic risk factors for type 1 diabetes (HLA-DRB1, -DQA1, and -DQB1 and insulin locus) play a role in the etiology of diabetic nephropathy. RESEARCH DESIGN AND METHODS; Genetic analysis of HLA-DRB1, -DQA1, -DQB1 and the insulin gene (INS) was ...

OBJECTIVE: Diabetic nephropathy, the most common cause of end-stage renal disease, aggregates in families and specific ethnic groups. Deconstructing diabetic nephropathy into intermediate, quantitative phenotypes may increase feasibility of detecting susceptibility loci by genetic screens. Glomerular filtration rate (GFR), which characterizes diabetic nephropathy, was employed as a quantitative trait in ...

OBJECTIVE: Diabetic nephropathy is damage to the kidney caused by diabetes mellitus. It is a common complication and a leading cause of death in people with diabetes. However, the decline in kidney function varies considerably between patients and the determinants of diabetic nephropathy have not been clearly identified. Therefore, it ...

Hyperhomocysteinemia (hHcys) has been recognized as a critical risk or pathogenic factor in the progression of end-stage renal disease (ESRD) and in the development of cardiovascular complications related to ESRD. Recently, evidence is accumulating that hHcys may directly act on glomerular cells to induce glomerular dysfunction and consequent glomerular sclerosis, ...

The activity of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of diabetic nephropathy. However, the effect of angiotensin-converting enzyme (ACE) inhibition on the RAAS appears to be modulated by a number of factors including the I/D polymorphism of the ACE genotype. In this study, ...

BACKGROUND: Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia ...

Diabetic nephropathy is the primary etiology of chronic kidney disease and kidney failure. With the incidence of type 2 diabetes rapidly increasing in the United States, it is imperative for health care professionals to clearly understand the mechanism of this condition and the implications for prevention. Early recognition of the ...

Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in ...

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality. Current renoprotective treatment for diabetic nephropathy includes strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection ...

Clinical practice guidelines from many professional societies endorse renin-angiotensin system (RAS) antagonists as first-line antihypertensive agents in diabetes and chronic kidney disease, largely based on putative renoprotective properties that may be blood pressure (BP) independent. To evaluate the relevance of these recommendations to early stage, nonproteinuric nephropathy, studies of primary ...

Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal models. In the present study we investigated the effects of LAB on the prevention of diabetic nephropathy in type 2 diabetic Otsuka Long-Evans-Tokushima Fatty (OLETF) rats. LAB ...

Proteomic methods have found broad applications in kidney disease research and more specifically in diabetic nephropathy (DN) research. Proteomic methods such as 2-dimensional gel electrophoresis have been used to gain insight into glomerular and tubular nephropathies including DN. At the protein level, differences in high-abundant proteins in DN have been ...

Diabetic nephropathy develops in only a subgroup of patients affected by type 1 diabetes. Once established, this complication is quite difficult to control, and consequently its prevention is presently considered the first target to achieve. As hyperglycemia has immediate effects on renal function and structure, it is reasonable to say ...

BACKGROUND: Patients with Type 2 diabetes and albuminuria are at high risk to progress to end-stage renal disease (ESRD). Although angiotensin receptor blockers confer renoprotection, many diabetic patients still develop overt nephropathy and reach ESRD. Glycosaminoglycans belong to the same family as heparin and heparinoids. Pilot studies with sulodexide, a ...

OBJECTIVE: Excessive production of reactive oxygen species (ROS) via NADPH oxidase has been implicated in the pathogenesis of diabetic nephropathy. Since NADPH oxidase activation is closely linked to other putative pathways, its interaction with changes in protein kinase C (PKC) and increased advanced glycation was examined. RESEARCH DESIGN AND METHODS: ...

BACKGROUND: Osteodystrophy is one of the long-term haemodialysis complications, and in diabetic patients, it mainly occurs as an aplastic or low-turnover type due to their low serum intact parathyroid hormone (iPTH) levels. In the present study, we investigated the role of glycaemic control to the serum iPTH levels in diabetic ...

The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGFbeta-1, fibronectin, and SPARC in the absence ...

Diabetic nephropathy is currently the leading cause of end-stage renal disease worldwide, and occurs in approximately one third of all diabetic patients. The molecular pathogenesis of diabetic nephropathy has not been fully characterized and novel mediators and drivers of the disease are still being described. Previous data from our laboratory ...

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 ...