Original Investigation Angiotensin Blockade and Progressive Loss of Kidney Function in Hemodialysis Patients: A Randomized Controlled Trial

Background: Glomerular filtration rate (GFR) declines during long-term dialysis treatment. In peritoneal dialysis, blockade of the renin-angiotensin-aldosterone system reduces GFR decline. Observational studies suggest that similar treatment may preserve kidney function in hemodialysis (HD). Study Design: A multicenter, randomized, placebo-controlled, double-blinded trial, with 1-year follow-up. Setting & Participants: Adult HD patients with urine output . 300 mL/24 h, HD vintage less than 1 year, and cardiac ejection fraction . 30%. Patients were included from 6 HD centers. Intervention: Patients were randomly assigned to placebo or the angiotensin II receptor blocker irbesartan, 300 mg daily. Target systolic blood pressure (BP) was 140 mm Hg. Outcomes & Measurements: Primary outcomes were change in GFR measured as the mean of creatinine and urea renal clearance together with urine volume. Secondary outcomes were change in albuminuria, reninangiotensin II-aldosterone hormone plasma levels, and time to anuria. Results: Of 82 patients randomly assigned (41 patients in each group), 56 completed 1 year of treatment. The placebo and irbesartan groups were comparable at baseline in terms of sex balance (26 vs 30 men), mean age (62 vs 61 years), median HD vintage (137 vs 148 days), mean HD time (10 vs 11 h/wk), median urine volume (1.19 vs 1.26 L/d), and mean GFR (4.8 vs 5.7 mL/min/1.73 m 2 ). The target BP level was reached in both groups and BP did not differ significantly between groups over time. Adverse-event rates were similar. GFR declined by a mean of 1.7 (95% CI, 1.2-2.3) and 1.8 (95% CI, 1.1-2.4) mL/min/1.73 m 2 per year in the placebo and irbesartan groups, respectively. Mean difference (baseline values minus value at 12 months) between groups was 20.0 (95% CI, 20.8 to 0.8). In each group, 4 patients became anuric. Limitations: GFR decline rates were lower than expected, reducing the power. Conclusions: At equal BP levels, we found that irbesartan treatment did not affect the decline in GFR or urine volume significantly during 1 year of treatment in HD patients. Irbesartan treatment was used safely in the studied population.