Renal allograft protection with angiotensin II type 1 receptor antagonists

Abstract

The renal benefits of agents inhibiting the renin-angiotensin-aldosterone system in renal transplant recipients, i.e. preventing the development of chronic graft nephropathy, are supposed but not finally proven. In a double-blind, placebo-controlled, cross-over study, we evaluated the influence of losartan on surrogate markers of tubular injury, urine excretion of transforming growth factor beta-1 (TGF-beta1) and amino-terminal propeptide of type III procollagen (PIIINP) in 16 patients after transplantation. The patients received randomly either losartan (50-100 mg daily) or the beta-blocker carvedilol (12.5-25 mg) for 8 weeks, allowing a placebo washout between treatments. The target office through blood pressure (BP) was below 130/85 mmHg. The BP did not differ in the treatment periods. Losartan significantly decreased N-acetyl-beta-d-glucosaminidase and alfa-1 microglobulin excretion relative to placebo and carvedilol. Urine excretion of TGF-beta1 and PIIINP was significantly lower after losartan. In conclusion, losartan reduces urine excretion of proteins associated with tubular damage and graft fibrosis.