ANGIOTENSIN-II ANTAGONISM IMPROVES THE LIPOPROTEIN PROFILE IN PATIENTS WITH NEPHROTIC SYNDROME

Objective: To study the effects of the angiotensin II receptor antagonist losartan on the lipid profile of patients with nephrotic range proteinuria. Design: A single-blind, longitudinal study. Patients were followed during four periods each lasting 1 month, in which they received in sequence once-daily placebo, 50 mg losartan, 100 mg losartan and placebo, respectively. Measurements were performed at the end of each study period. Patients: Eleven patients with biopsy-proven renal disease, diastolic blood pressure greater than or equal to 90 mmHg, creatinine clearance greater than or equal to 50 ml/min, stable proteinuria greater than or equal to 2.5 g/day, without familial hyperlipidemia or use of hypolipidemic agents. Results: At the end of the 100 mg losartan period, median arterial blood pressure had fallen from 114.5 +/- 2.3 mmHg at baseline to 96 +/- 2.8 mmHg (P < 0.001). Urinary protein excretion decreased from 6.2 +/- 1.3 g/day to 4.2 +/- 1.3 g/day (P < 0.001), whereas serum albumin and total protein did not change. Total cholesterol fell significantly from 6.67 +/- 0.46 mmol/l to 6.08 +/- 0.42 mmol/l (P = 0.04). This decrease in cholesterol was mainly due to a decrease in very-low-density and low-density lipoprotein cholesterol, though high-density lipoprotein cholesterol also tended to fall. Apolipoprotein B decreased by 13.0 +/- 3.6% (P = 0.05), whereas the apolipoprotein At concentration remained unchanged, thus resulting in a significant increase in the apolipoprotein A(1)/B ratio (12.5 +/- 3.5%, P = 0.05). Lipoprotein(a) concentration Tell from 287 +/- 57 mg/l to 218 +/- 35 mg/l (P = 0.07). Interestingly, those patients that had the highest baseline lipoprotein(a) values showed the most outspoken change in lipoprotein(a) levels during treatment. In the placebo recovery period all parameters returned towards baseline values. Conclusions: In addition to lowering blood pressure and proteinuria, the angiotensin II antagonist losartan improves the lipoprotein profile in patients with nephrotic range proteinuria.