Losartan decreases plasma levels of TGF-beta 1 in transplant patients withchronic allograft nephropathy

Background Chronic allograft nephropathy represents the principal cause of graft loss after the first year of transplantation. Transforming growth fac tor-beta 1 (TGF-beta 1) is a key factor in fibrogenesis and has been involv ed in the pathogenesis of chronic allograft nephropathy and other chronic n ephropathies. Experimental studies have demonstrated that the angiotensin I I receptor antagonist (losartan) could decrease the synthesis of TGF-beta 1 . The aim of this study was to determine the plasma levels of TGF-beta 1 in transplant patients with chronic allograft nephropathy, and to evaluate th e effect of losartan on TGF-beta 1 plasma levels and other vasoactive pepti des (angiotensin II, plasma renin activity, aldosterone, endothelin-1, and nitrites and nitrates). Angiotensin-converting enzyme genotypes were also d etermined in all patients. Methods. Fourteen transplant patients with chronic allograft nephropathy we re included. Treatment with losartan (50 mg) was introduced. Consecutive de terminations of TGF-beta 1 and other vasoactive peptides were performed dur ing follow-up. Results. Patients with chronic allograft nephropathy presented higher plasm a levels of TGF-beta 1 than the control groups. The treatment with losartan significantly decreased the plasma levels of TGF-beta 1 (P < 0.05) and end othelin (P < 0.05) in all patients. The decrease of TGF-beta 1 was statisti cally correlated with the blockade of the angiotensin II receptor (P < 0.05 ). No significant correlation could be demonstrated between angiotensin-con verting enzyme genotypes and TGF-beta, endothelin-1, and nitrite-nitrate se rum levels. Conclusions. This study demonstrates that losartan significantly decreases the plasma levels of TGF-beta 1, the most important fibrogenetic factor. Th ese results could play a decisive role in the treatment and prevention of c hronic nephropathies, not only graft nephropathy, because the intrinsic pat hogenetic mechanism is very similar in all forms, with a crucial roles for the renal renin-angiotensin system and TGF-beta 1.