Effect of pirfenidone against vanadate-induced kidney fibrosis in rats.

ABSTRACT

Renal fibrosis is a complication of kidney injury and can contribute to organ failure. Currently, there are no drugs for the treatment of renal fibrosis. Pirfenidone (PD) has been proven to have antifibrotic effects in animal models of fibrosis. We tested the ability of PD against vanadate-induced kidney fibrosis in rats. The rats were injected subcutaneously with vehicle or vanadate solution (1mg vanadate/kg/day) for 12 or 16 days to produce varying degrees of kidney fibrosis. The vanadate- and vehicle-treated rats were fed a laboratory diet or the same diet mixed with 0.6% PD ad lib. One vanadate-injected group was initially fed the same diet without PD and later switched to the diet containing PD 2 days after the last injection. The rats were killed at 12 and 25 days following the last dose. The changes found in the kidney of vanadate-treated rats included increases in RNA and DNA content and increases in kidney weight. Treatment with PD diminished the vanadate-induced increases in kidney weight and RNA content. The hydroxyproline content of the kidney in vanadate-treated animals was increased significantly (P< or =0.05) from the control level of 1452 microg/kidney to 1765 microg/kidney. Treatment with PD for 37 days caused significant reductions in the vanadate-induced increases in the hydroxyproline level. Similarly, treatment for 41 days also caused significant reductions (1744 microg/kidney) in vanadate-induced increases in the hydroxyproline level (1996 microg/kidney). The histological evaluation revealed that the severity of the lesions in the vanadate-treated group was moderate to severe, and treatment with PD for 41 days decreased the severity to a mild level. In addition, the delayed treatment with PD also minimized the vanadate-induced increases in the collagen content of the kidney. Although it is speculative, PD may potentially be therapeutic in the management of renal fibrosis.