The antiproteinuric effects of blood pressure-lowering agents: differences between nondiabetics and diabetics

The mechanism of the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors in diabetic and nondiabetic renal disease is as yet unknown. A meta-analysis of studies on the effects of ACE inhibitors and other antihypertensive drugs on proteinuria, blood pressure, and renal hemodynamics in nondiabetic renal disease revealed that ACE inhibitors lower proteinuria more than other antihypertensives. Moreover, a close correlation (p less than 0.01) between changes in urinary protein loss and in filtration fraction was found, whereas such a correlation could not be detected between changes in proteinuria and in blood pressure. This suggests that, at least in nondiabetic renal disease, the fall in proteinuria during ACE inhibition is the consequence of the intrarenal effect of the drug more than the systemic effect. Data on the mechanism of action of ACE inhibitors in diabetic microalbuminuria and in diabetic overt proteinuria are less consistent. A fall in proteinuria on antihypertensive drugs in these patients can be observed also without a significant fall in blood pressure, and without any change in filtration fraction. We therefore conclude that one should be cautious in extrapolating the data from studies in diabetic renal disease to patients with nondiabetic nephropathies. Moreover, we argue also that nonhemodynamic effects of ACE inhibitors also could be involved in the antiproteinuric effect of these drugs.