Pirfenidone prevents the progression of irreversible glomerular sclerotic lesions in rats

Abstract

Summary: Pirfenidone (PFD) is a new drug which has been shown to prevent or even reverse the extracellular matrix accumulation in several organs. to examine the effect of PFD on the progressive glomerulosclerosis, we treated model rats with irreversible chronic renal disease per orally with 500 mg/kg bodyweight of PFD per day. the model rats were made by intravenous injection of anti‐Thy‐1 monoclonal antibody 1‐22‐3 at 1 h following unilateral nephrectomy, which results in chronic progressive glomerulosclerosis. Twenty‐four hours later, 32 female Wistar rats were divided into two groups and were fed standard chow with (PFD group: P) or without PFD (control group: C). All rats were sacrificed on day 42. No significant difference in the bodyweight or the amount of chow intake was observed between the two groups. the remnant kidney was significantly (P<0.05) heavier in C (2.11 ± 0.15 g) than in P (1.70 ± 0.13 g). This finding, together with light microscopic findings, showed that PFD administration resulted in the prevention of renal hypertrophy. On day 42, proteinuria in P (124.3 ± 31.9 mg/day) was significantly lower than in C (214.6 ± 8.1 mg/day), and P maintained significantly better renal function than C as judged by serum urea nitrogen and creatinine levels. Mean matrix score was less in P (178 ± 17) than in C (225 ± 22). Crescent formation was observed in 17% of glomeruli in P and in 35% in C. Tubulointerstitial lesions were also less severe in P. Furthermore, inflammation and sclerosis indices detected by immunohistochemistry (e.g. ED‐1, OX8, TGF‐beta α‐smooth muscle actin, collagen type I, were less in P). These data suggest that PFD may be a promising agent for the prevention of progressive and irreversible glomerulosclerosis.