Losartan decreases plasma levels of TGF-β1 in transplant patients with chronic allograft nephropathy

Abstract

Background. Chronic allograft nephropathy represents the principal cause of graft loss after the first year of transplantation. Transforming growth factor-β1 (TGF-β1) is a key factor in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy and other chronic nephropathies. Experimental studies have demonstrated that the angiotensin II receptor antagonist (losartan) could decrease the synthesis of TGF-β1. The aim of this study was to determine the plasma levels of TGF-β1 in transplant patients with chronic allograft nephropathy, and to evaluate the effect of losartan on TGF-β1 plasma levels and other vasoactive peptides (angiotensin II, plasma renin activity, aldosterone, endothelin-1, and nitrites and nitrates). Angiotensin-converting enzyme genotypes were also determined in all patients. Methods. Fourteen transplant patients with chronic allograft nephropathy were included. Treatment with losartan (50 mg) was introduced. Consecutive determinations of TGF-β1 and other vasoactive peptides were performed during follow-up. Results. Patients with chronic allograft nephropathy presented higher plasma levels of TGF-β1 than the control groups. The treatment with losartan significantly decreased the plasma levels of TGF-β1 (P < 0.05) and endothelin (P < 0.05) in all patients. The decrease of TGF-β1 was statistically correlated with the blockade of the angiotensin II receptor (P < 0.05). No significant correlation could be demonstrated between angiotensin-converting enzyme genotypes and TGF-β, endothelin-1, and nitrite-nitrate serum levels. Conclusions. This study demonstrates that losartan significantly decreases the plasma levels of TGF-β1, the most important fibrogenetic factor. These results could play a decisive role in the treatment and prevention of chronic nephropathies, not only graft nephropathy, because the intrinsic pathogenetic mechanism is very similar in all forms, with a crucial roles for the renal renin-angiotensin system and TGF-β1.