Renal
fibrosis is the final common pathway of
chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of
pirfenidone in a remnant kidney model of
chronic renal failure to determine its pharmacological potency compared to
enalapril. Five-sixths nephrectomized rats were fed diet containing
pirfenidone (approximately 700mg/kg/day) for 8weeks.
Pirfenidone steadily inhibited the progression of
proteinuria, but not to a significant degree.
Pirfenidone prevented the elevation of plasma
creatinine and blood
urea nitrogen. At the end of the experiment,
pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study,
pirfenidone improved interstitial
fibrosis in the renal cortex. These effects were supported by the suppression of the expression of
TGF-beta and
fibronectin in the
mRNA of the kidney. In contrast,
pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the
proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the
TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that
pirfenidone improves the progression of
chronic renal failure via its antifibrotic action, although
pirfenidone has less effective
TGF-beta-induced epithelial to mesenchymal transdifferentiation.