TGF-beta 1 production in radiation nephropathy: role of angiotensin II

Purpose: Angiotensin II receptor antagonists are effective in the prophylax is of radiation nephropathy. Studies were designed to determine whether TGF -beta 1, a fibrogenic cytokine, plays a role in mediating the protective ef fect of AII antagonism. These studies explored the time-course of glomerula r TGF-beta 1 production in the irradiated kidney, and whether AII mediates TGF-beta 1 production in glomeruli isolated from irradiated rats. Materials and methods: Rats received 20 Gy of bilateral renal irradiation i n five fractions and were randomized to receive an AII type 1 receptor anta gonist (L-158,809) at 20 mg/l in their drinking water, or no treatment. Dru g therapy began 9 days prior to irradiation and continued for the duration of the study. Results: Analysis of renal function showed a significant increase in urinar y proteinuria and blood urea nitrogen by 37 days and 63 days after irradiat ion, respectively. Estimation of glomerular TGF-beta 1 levels by quantitati ve sandwich enzyme immunoassay technique revealed a significant increase in latent but not active TGF-beta 1 levels at 50 days and 63 days after irrad iation. In animals treated with the ATI receptor antagonist, there was a co mplete elimination in the rise of TGF-beta 1. Conclusions: These studies demonstrate that glomerular TGF-beta 1 productio n is elevated in the course of radiation nephropathy, and that AII mediates this induction of TGF-beta 1.