A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion >500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) <2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (<140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a >50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean ±SD): male/female, 52%/48%; age, 35 ± 8 yr; duration of diabetes, 21 ± 7 yr; duration of proteinuria, 2.8 ± 3.3 yr; duration of retinopathy, 4.5 ± 4.1 yr; 50% of cohort presented with hypertension, duration, 4 ± 4.7 yr; blood pressure, 139/86 ± 19/12; SCr, 1.35 ± 0.44 mg/dL; GFR 78 ± 32 mL/min; BUN, 24 ± 11 mg/dL; proteinuria, 3.1 ± 3.3 g/day; cholesterol, 236 ± 50 mg/dL; total glycosylated hemoglobin, 11.1 ± 2.1%. Analysis of baseline data with entry GFR yielded the following univariate linear associations: GFR had a weak but significant inverse correlation with urine protein/creatinine ratio (r2 = 0.19), entry systolic blood pressure (-0.62 mL/min/1.73 m2/mm Hg; r2 = 0.13), age at entry (-1.2 mL/min/yr; r2 = 0.07), and serum cholesterol (r2 = 0.09). GFR was not correlated with duration of diabetes (r2 = 0.006), percentage of life as a diabetic (r2 = 0.02), or blood glycohemoglobin (r2 = 0.007). The elements of a controlled clinical trial are described. The baseline entry data confirm an association between reduced GFR and increasing hypertension, proteinuria, and cholesterolemia but not duration of diabetes, percentage of life as a diabetic, or severity of hyperglycemia.
|Journal||Journal of the American Society of Nephrology|
|Issue number||4 SUPPL.|
|State||Published - Oct 1 1992|
- Angiotensin-converting enzyme inhibition
- Diabetes mellitus
- Diabetic nephropathy