Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-β1 plasma levels in a crossover trial in renal transplant recipients

Abstract

Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-β1 (TGF-β1) is the main cytokine involved in the fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-β1 production. Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-β1 production in renal transplant patients. The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics, as well as TGF-β1 and endothelin-1 (ET-1) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine. Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a random 2 × 2 crossover trial with amlodipine and losartan (6 wk with each therapy). Three studies were performed (at baseline and at the end of both treatment periods) to determine renal hemodynamics, TGF-β1, and ET-1. Both treatments controlled BP to a similar degree, but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction. In contrast, losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly. Losartan and amlodipine had opposite effects on TGF-β1. Amlodipine did not affect TGF-β1 concentrations. In contrast, losartan reduced the plasma levels of TGF-β1 by approximately by 50% (from baseline, 5.2 to 2.6 ng/ml; P = 0.01); the majority of the patients reached normal levels of TGF-β1. ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. The present study documents that with similar control of BP, losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-β1 concentrations. These differences could be important for the management of chronic allograft nephropathy.