Low-dose dual blockade of the renin-angiotensin system in patients with primary glomerulonephritis

Background: Treatment with agents interfering with the renin-angiotensin system retards the progressive course of proteinuric chronic renal disease. However, because of unwanted effects associated with such therapy, some patients cannot be treated with these drugs at all or may be administered only very small doses. To find an optimal nephroprotective strategy for these patients, we compared antiproteinuric effects of combination therapy with an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist in very small doses with treatment with either agent alone at greater, but not maximal, doses. We compared the concomitant use of benazepril, 5 mg, and losartan, 25 mg, and monotherapy with these agents in doses 2-fold greater. Methods: This is a randomized, open, crossover study of 3 treatments in 3 periods of 4 months each. Twenty-four patients with primary glomerulonephritis and nonnephrotic proteinuria, recognized previously as not able to be administered high doses of drugs from these classes, completed the protocol. Results: Combined therapy decreased 24-hour proteinuria (-45.54% versus baseline) more effectively than either losartan (-28.17%; analysis of variance, P < 0.01) or benazepril (-20.19%; analysis of variance, P < 0.001) alone. Subgroup analysis showed that antiproteinuric effects of combination therapy, as well as losartan or benazepril alone, were significantly greater in patients with basal proteinuria greater than 2 g/24 h than in those with proteinuria less than this value (P < 0.001, P < 0.01, and P < 0.05, respectively). All therapies significantly decreased blood pressure (BP) compared with baseline, but there were no differences between treatments in BP changes. Conclusion: The study shows that combination therapy with very small doses of losartan and benazepril was more effective in reducing proteinuria than greater doses of either agent in monotherapy, and this greater antiproteinuric efficacy was independent of changes in BP.