Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-ss(1) plasma levels in a crossover trial in renal transplant recipients

Hypertension and hyperfiltration are two important risk factors for the dev elopment of chronic allograft nephropathy, Transforming growth factor-beta (1) (TGF-beta (1)) is the main cytokine involved in the fibrotic process th at is involved in chronic rejection. Angiotensin II upregulates TGF-beta (1 ) production. Angiotensin IT receptor antagonists therefore could not only control BP but also reduce TGF-beta (1) production in renal transplant pati ents. The aim of this study was to compare the effects of losartan and amlo dipine on renal hemodynamics, as well as TGF-beta (1) and endothelin-1 (ET- 1) plasma levels in a group of renal transplant patients who had normal ren al function and who were treated with cyclosporine. Seventeen renal transpl ant patients who were receiving cyclosporine and who had normal graft funct ion were included in a random 2 x 2 crossover trial with amlodipine and los artan (6 wk with each therapy). Three studies were performed (at baseline a nd at the end of both treatment periods) to determine renal hemodynamics, T GF-beta (1), and ET-1. Both treatments controlled BP to a similar degree, b ut only amlodipine increased GFR through an increase in the estimated glome rular hydrostatic pressure and filtration fraction. In contrast, losartan m aintained GFR and reduced estimated glomerular hydrostatic pressure and fil tration fraction significantly. Losartan and amlodipine had opposite effect s on TGF-beta (1). Amlodipine did not affect TGF-beta (1) concentrations. I n contrast, losartan reduced the plasma levels of TGF-beta (1) by approxima tely by 50% (from baseline, 5.2 to 2.6 ng/ml; P = 0.01); the majority of th e patients reached normal levels of TGF-beta (1). ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. Th e present study documents that with similar control of BP, losartan and aml odipine have opposite effects on renal hemodynamics and on TGF-beta1 concen trations. These differences could be important for the management of chroni c allograft nephropathy.