The functional characteristics of the renal glomerulus have been investigated in Pima Indians of the Gila River Indian Community to identify the underlying pathogenetic mechanisms involved in the initiation and progression of renal disease in non-insulin-dependent diabetes mellitus (NIDDM). A randomized, double-blinded, placebo-controlled clinical trial will be performed in diabetic Pima Indians with normal urinary albumin excretion or early microalbuminuria to test the hypothesis that blockade of the renin-angiotensin system can prevent or attenuate the development and progression of early diabetic nephropathy (RPF) and fractional clearances of albumin and IgT will be made. Masked treatment with drug or placebo will be converted to active treatment in those who develop macroalbuminuria (albumin-to-creatinine ratio greater than or equal to 300 mg/g), but both the patient and the investigators will remain blinded to the previous treatment. Kidney biopsies will be performed after five years in 30 subjects who initially had normoalbuminuria and will be selected equally from the drug and placebo groups. Morphometric analysis will be used to determine differences in the prevalence of global sclerosis, the breadth of epithelial foot processes, and the fractional mesangial volume between treatment groups. The major outcome measure will be renal insufficiency and subjects will be followed to this endpoint. Other measures of renoprotection that will be assessed are 1) change in albumin excretion, 2) change in GFR, and 3) glomerular morphology. This project, in part, represents an extension of work previously reported as Project Number Z01 DK 69037.
| Lemley, K V; Abdullah, I; Myers, B D et al. (2000) Evolution of incipient nephropathy in type 2 diabetes mellitus. Kidney Int 58:1228-37 |
| Lemley, K V; Blouch, K; Abdullah, I et al. (2000) Glomerular permselectivity at the onset of nephropathy in type 2 diabetes mellitus. J Am Soc Nephrol 11:2095-105 |
| Nelson, R G; Tan, M; Beck, G J et al. (1999) Changing glomerular filtration with progression from impaired glucose tolerance to Type II diabetes mellitus. Diabetologia 42:90-3 |
| Meyer, T W; Bennett, P H; Nelson, R G (1999) Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria. Diabetologia 42:1341-4 |
