Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy

Hypertension is a common finding in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. African Americans have a high prevalence of NIDDM and hypertension, and are relatively resistant to the antihypertensive effects of converting enzyme inhibitors (CEI) but respond well to calcium channel blockers (CCB). In the long-term study presented here, the effects of isradipine, a dihydropyridine calcium antagonist, on the course of the nephropathy were investigated and compared with the effects of captopril in 31 African Americans with NIDDM and proteinuria (≤500 mg/day). The patients were stratified by levels of GFR and proteinuria, and they were randomized to receive isradipine (N = 16) or captopril (N = 15); doses were adjusted to maintain similar BP levels (<140/90). At 6 months, mean arterial pressure was similar (102 ± 3 and 104 ± 3 mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged (Δ = -4 ± 3 and +1 ± 3 ml/min/1.73 in the isradipine and captopril groups, respectively; P = NS). However, proteinuria in the isradipine group increased by approximately 50% (2.01 ± 0.40 versus 3.04 ± 0.70 mg/mg creatinine at baseline versus 6 months, respectively, P < 0.05), whereas captopril reduced proteinuria by 30% after 6 months (2.85 ± 0.70 at baseline versus 2.30 ± 0.70 mg/mg creatinine, P < 0.05). Dietary protein, sodium intake, and HbA(1C) levels were similar in both groups and did not differ from baseline. It was concluded that over 6 months, captopril reduces and isradipine increases proteinuria in African Americans with NIDDM and nephropathy. Whether this contrasting effect on proteinuria will result in different rates of progression is not known, but dihydropyridine CCB should be used cautiously in African Americans with diabetic nephropathy.