PREVENTION OF DIABETIC NEPHROPATHY IN IDDM

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This proposal requests support for a clinical study designed to see whether lowering the hyperfiltration that occurs in early insulin dependent diabetes mellitus and inhibition of angiotensin II converting enzyme will reverse microalbuminuria and prevent the progressive decline in glomerular filtration rate that has been documented in other studies of insulin dependent diabetes. We have available 263 cases of insulin dependent diabetes presently in a longitudinal study of the natural history of diabetic retinopathy by the Department of Ophthalmology. Nearly 70 percent of the subjects do not have proteinuria detectable by routine clinical procedures. In these individuals without proteinuria, the rate of microalbuminuria will be characterized by an albumin radioimmunoassay of timed urine collections and those individuals with albumin excretion rates in excess of 15 micrograms/min will be randomized into two groups. One group will be patients with early microalbuminuria (15 to 80 micrograms/min) and the second group will contain those individuals with microalbumin excretion rates ranging between 81 and 250 micrograms of albumin per minutes. No individual with a blood pressure greater than 140/85 or who is receiving antihypertensive therapy will be included. Each of the two groups will be randomized into a treatment group and a control group and the treatment group given converting enzyme inhibitors at a level of 20 mg/day. Microalbumin excretion rates will be measured every three months and glomerular filtration rates every six months and assessment of retinal changes will be made on an annual basis. Observations will be made over a period of three years following initiation of treatment. Outcome variables will be microalbumin excretion rate, change in GFR and change in the severity of retinopathy. This study should provide a direct test of the hypothesis that the hyperprofusion of the glomeruli in early diabetes mellitus play an important pathogenetic role in the production of diabetic nephropathy.