How to Attain Optimal Antiproteinuric Dose of Losartan in Non-Diabetic Patients with Nephrotic Range Proteinuria

Abstract

Although the antiproteinuric response to antihypertensive treatment is the main predictor of renoprotective efficacy in long-term renal disease, dose finding studies of antihypertensives have only been based on blood pressure so far. The present study aimed to find the optimal antiproteinuric dose of the angiotensin II antagonist losartan. An open-label dose-response study using subsequent six-week treatment periods was performed in ten non-diabetic patients with proteinuria (Uprot) of 5.8 ± 0.8 g/d and a mean arterial pressure (MAP) of 103 ± 3.7 mmHg without antihypertensive medication. All patients had a normal to moderately impaired renal function. After the baseline period, five periods followed with respectively a daily losartan dose of 50 mg, 100 mg, 150 mg, again 50 mg, and a recovery without losartan. At the end of each period, Uprot and MAP were measured. The consecutive doses of losartan had a similar antihypertensive response (−11.3 f 2.8% at the 100 mg dose). The optimal antiproteinuric response was reached at 100 mg losartan (−30 ± 8%). The 50 mg dose (−13 ± 7%) was less effective and the 150 mg dose (−28 ± 8%) was not more effective. We conclude that 100 mg losartan is the optimal dose for reduction of proteinuria in non-diabetic patients with nephroticrange proteinuria.