A molecular morphometric approach to diabetic kidney disease can link structure to function and outcome.

Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes.

White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes.

Background: Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study.

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.

We examined associations of advanced glycation end products (AGEs) with renal function loss (RFL) and its structural determinants in American Indians with type 2 diabetes. Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan. Participants remained under observation after the trial concluded.

Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes.

Aims: Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic nephropathy (DN). We investigated the relationship between DN structural lesions and CAN.

Methods: Sixty three Pima Indians with type 2 diabetes underwent kidney biopsies following a 6-year clinical trial testing the renoprotective efficacy of losartan vs.

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

Background And Objectives: Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued.

Effect of losartan on prevention and progression of early diabetic nephropathy in American Indians with type 2 diabetes.

Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30-299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to ≤60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min.

Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy.

Podocyte detachment and reduced endothelial cell fenestration and relationships between these features and the classic structural changes of diabetic nephropathy have not been described in patients with type 2 diabetes. Here we studied these relationships in 37 Pima Indians with type 2 diabetes of whom 11 had normal albuminuria, 16 had microalbuminuria, and 10 had macroalbuminuria. Biopsies from 10 kidney donors (not American Indians) showed almost undetectable (0.

Podocyte detachment in type 2 diabetic nephropathy.

Background: Glomerular podocyte number declines and urinary excretion of podocytes increases as kidney disease progresses in persons with type 2 diabetes mellitus (T2DM).

Methods: Using high-power electron microscopy, we quantified podocyte detachment in T2DM.

Results: We evaluated 106 glomeruli (range 1-6 per subject) from 40 Pima Indian subjects with T2DM enrolled in a clinical trial.

Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy.

Objective: Glomerular mesangial expansion and podocyte loss are important early features of diabetic nephropathy, whereas tubulointerstitial injury and fibrosis are critical for progression of diabetic nephropathy to kidney failure. Therefore, we analyzed the expression of genes in glomeruli and tubulointerstitium in kidney biopsies from diabetic nephropathy patients to identify pathways that may be activated in humans but not in murine models of diabetic nephropathy that fail to progress to glomerulosclerosis, tubulointerstitial fibrosis, and kidney failure.

Research Design And Methods: Kidney biopsies were obtained from 74 patients (control subjects, early and progressive type 2 diabetic nephropathy).

The process of implementing a CKD clinic.

Chronic kidney disease patients are complex, and usually have multiple comorbid conditions. It is evident that a CKD clinic can improve clinical outcomes and patient satisfaction. It is widely recognized that education, patient empowerment, early recognition of the disease, and appropriate and timely interventions in patients with CKD can positively influence the clinical outcomes in this population.