Angiotensin-converting enzyme inhibitors in diabetes: effect on the kidney and on blood pressure.

Abstract

In diabetes mellitus, studies on the renin angiotensin system conflict. Among type I diabetic patients, we have found normal plasma renin activity and angiotensin II levels. In these patients, low-dose angiotensin II infusion resulted in the same effect on renal hemodynamics as that observed in healthy controls. In patients with diabetic nephropathy, a disease usually regarded as a low-renin condition, we have found elevated levels of plasma renin activity as compared with that seen in healthy persons and control subjects with other renal diseases that result in a similar degree of renal failure. In patients with diabetic nephropathy, interruption of the renin angiotensin system with angiotensin-converting enzyme inhibitors has been associated with a reduction in proteinuria. It is not clear whether this is a result of blood pressure reduction or a specific effect of these drugs. In a randomized trial with patients with diabetic nephropathy, we found that enalapril treatment reduced proteinuria to less than half the level obtained in a metoprolol-treated group during equally effective blood pressure control. In a long-term prospective study of captopril in patients with diabetic nephropathy, the rate of decline in kidney function was reduced to half the value that was calculated during a retrospective period. The renin angiotensin system, therefore, can be normally active in patients with diabetic nephropathy, and angiotensin-converting enzyme inhibitors can reduce proteinuria by mechanisms independent of their effect on blood pressure. Long-term treatment may protect renal function to a greater degree than might be expected from the blood pressure-lowering effect.