Randomized Placebo-Controlled Study on the Effects of Losartan and Carvedilol on Albuminuria in Renal Transplant Recipients

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.