Detection of Angiotensin II type I-receptor antibodies in transplant glomerulopathy.

Background: Transplant glomerulopathy (TG) is an important cause of late graft loss. The role of angiotensin type 1-receptor antibodies (AT R-Ab) in TG is not known.

Methods: All the TG cases (N = 137) between January 2007 and December 2014 (N = 1410) were analyzed.

Incidence of prolonged QTc and severe hypoglycemia in type 1 diabetes: the EURODIAB Prospective Complications Study.

Aims: To assess the independent role of severe hypoglycemia on 7-year cumulative incidence of prolonged QTc in a large cohort of patients with type 1 diabetes.

Methods: People with type 1 diabetes recruited by the EURODIAB Prospective Complications Study who had normal QTc were examined at baseline and after 7 years with standardized methods (n = 1415; mean age ± SD 32.1 ± 9.

Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells.

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of acute kidney injury (AKI) in a manner comparable with the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSCs, it is unclear which population is responsible for the proregenerative effects. We therefore evaluated the effect of various EV populations separated by differential ultracentrifugation (10K population enriched with microvesicles and 100K population enriched with exosomes) on AKI recovery.

Circulating anti-Hsp70 levels in nascent metabolic syndrome: the Casale Monferrato Study.

The metabolic syndrome (MetS) confers an increased risk of both type 2 diabetes and cardiovascular diseases (CVD). Heat shock protein 70 (Hsp70), an intracellular polypeptide, can be exposed on the plasma membrane and/or released into the circulation, eliciting both native and immune responses that may contribute to vascular damage. Our aim was to assess if serum anti-Hsp70 antibody levels were cross-sectionally associated with uncomplicated MetS.

Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based Casale Monferrato Study.

Objective: To evaluate the predictive role of increased corrected QT (QTc) and QT interval dispersion (QTd) on all-cause and cardiovascular mortality in a large, unselected type 2 diabetic population.

Research Design And Methods: The prospective study included 1,357 type 2 diabetic patients from the Casale Monferrato Study. At baseline, QTc intervals >0.

QTc interval prolongation is independently associated with severe hypoglycemic attacks in type 1 diabetes from the EURODIAB IDDM complications study.

Objective: Our aim was to assess whether severe hypoglycemic attacks were cross-sectionally associated with abnormalities of the QTc interval in type 1 diabetic patients.

Research Design And Methods: The study included 3,248 type 1 diabetic patients from the EURODIAB IDDM Complications Study. Severe hypoglycemia was defined as an attack serious enough to require the help of another person.

The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse.

Diabetic nephropathy is a leading cause of end-stage renal disease. Statins may exert renoprotective effects independently of lipid-lowering properties. We investigated the pleiotropic effects of rosuvastatin on renal structure and function in streptozotocin diabetic apolipoprotein-E knockout (Apo-E(-/-)) mice, a model of progressive nephropathy in which dyslipidemia is resistant to statin treatment.

Targeting the MCP-1/CCR2 System in diabetic kidney disease.

Diabetic nephropathy is the leading cause of end-stage renal failure in the Western World and accounts for significant morbidity and mortality in patients with diabetes. Although hyperglycaemia and hypertension are established key determinants in the development of the complication, recent studies suggest that a low-grade inflammatory response may also play a role. Monocyte Chemoattractant Protein 1 (MCP-1), a potent chemokine produced by renal cells, has emerged as a very important player in this process.

Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes.

Objective: Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes.

Heat shock protein expression in diabetic nephropathy.

Heat shock protein (HSP) HSP27, HSP60, HSP70, and HSP90 are induced by cellular stresses and play a key role in cytoprotection. Both hyperglycemia and glomerular hypertension are crucial determinants in the pathogenesis of diabetic nephropathy and impose cellular stresses on renal target cells. We studied both the expression and the phosphorylation state of HSP27, HSP60, HSP70, and HSP90 in vivo in rats made diabetic with streptozotocin and in vitro in mesangial cells and podocytes exposed to either high glucose or mechanical stretch.

Incidence and risk factors of prolonged QTc interval in type 1 diabetes: the EURODIAB Prospective Complications Study.

Objective: Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and diabetic populations. As part of the EURODIAB Prospective Complication Study, we have assessed the 7-year incidence and risk factors of prolonged QTc in people with type 1 diabetes.

Research Design And Methods: A total of 1,415 type 1 diabetic subjects, who had normal QTc at baseline, were reanalyzed after the 7-year follow-up period.

Lack of the antioxidant enzyme glutathione peroxidase-1 accelerates atherosclerosis in diabetic apolipoprotein E-deficient mice.

Background: Recent clinical studies have suggested a major protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx1) in diabetes-associated atherosclerosis. We induced diabetes in mice deficient for both GPx1 and apolipoprotein E (ApoE) to determine whether this is merely an association or whether GPx1 has a direct effect on diabetes-associated atherosclerosis.

Methods And Results: ApoE-deficient (ApoE-/-) and ApoE/GPx1 double-knockout (ApoE-/- GPx1-/-) mice were made diabetic with streptozotocin and aortic lesion formation, and atherogenic pathways were assessed after 10 and 20 weeks of diabetes.

Urinalysis: do not forget this type of cell in renal transplantation.

Microscopic sediment analysis of urine from a 56-year-old woman who underwent renal transplantation showed many uncommon clusters of rounded and translucent cells containing globular mucous cytoplasmic inclusions (HPF, x400). These cells were bigger than leukocytes and, compared with uroepithelial cells, showed a smaller nucleus to cytoplasm ratio and appeared eosinophilic, being pink rather than azurophilic with Sternheimer-Malbin stain. They were also unlikely to be tubular cells, which are usually smaller, singly distributed and associated with dysmorphic erythrocytes and/or casts and/or a worsening in renal function.

Effects of mechanical stress and high glucose on pericyte proliferation, apoptosis and contractile phenotype.

Pericyte loss is an early step of diabetic retinopathy. High glucose induces apoptosis in retinal pericytes, but systemic and capillary hypertension are also believed to be important in the onset and progression of diabetic retinopathy. The haemodynamic insult of retinal capillary hypertension can be mimicked by exposing pericytes to mechanical stretch.

PPAR-alpha and -gamma agonists attenuate diabetic kidney disease in the apolipoprotein E knockout mouse.

Background: Peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists are widely used in diabetes. In addition to their effects on lipid and glucose homeostasis, these agents have been postulated to have independent renoprotective actions. In the current study, we assess the efficacy of the PPAR-alpha agonist, gemfibrozil, the PPAR-gamma agonist rosiglitazone and the non-thiazolidinedione PPAR-alpha/gamma coagonist, compound 3q, on kidney structure and function in streptozotocin-treated apolipoprotein E knockout mice.

Management strategies for patients with hypertension and diabetes: why combination therapy is critical.

Hypertension is commonly associated and acts synergistically with diabetes in increasing the risk of macrovascular and microvascular diabetic complications. Large-scale clinical trials have demonstrated that this risk is significantly reduced by intensive antihypertensive treatment, and accordingly, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guideline has further lowered the blood pressure goals for diabetic subjects to <130/80 mm Hg. This implies that most diabetic patients will require the combination of two or more antihypertensive agents to achieve this blood pressure target.

Angiopoietin 2 induces cell cycle arrest in endothelial cells: a possible mechanism involved in advanced plaque neovascularization.

Objective: To characterize the molecules and the mechanisms regulating the neoangiogenetic process in advanced atherosclerotic plaques.

Methods And Results: Western blot and immunofluorescence analysis of atherosclerotic specimens demonstrated that unlike neovessels from early lesions that expressed vascular endothelial growth factor (VEGF) and angiopoietin1 (Angio1), vessels from advanced lesions expressed VEGF and angiopoietin 2 (Angio2). Moreover, only few neovessels from advanced lesions showed a positive immunostaining for proliferating cell nuclear antigen.

Prevalence of Q-T interval dispersion in type 1 diabetes and its relation with cardiac ischemia : the EURODIAB IDDM Complications Study Group.

Objective: The interlead variation in duration of the Q-T interval on the surface electrocardiogram (Q-T interval dispersion [QTd]) has been shown to predict mortality in type 2 diabetic patients. We evaluated the prevalence of QTd prolongation in the EURODIAB population and its relation to corrected Q-T interval (QTc), sex, age, duration of diabetes, blood glucose control, and complications. RESEARCH DESIGN AND METHODS; A total of 3,042 type 1 diabetic patients were studied.