PIRFENIDONE PREVENTS THE PROGRESSION OF IRREVERSIBLE GLOMERULAR SCLEROTIC LESIONS IN RATS

Pirfenidone (PFD) is a new drug which has been shown to prevent or eve n reverse the extracellular matrix accumulation in several organs. To examine the effect of PFD on the progressive glomerulosclerosis, we tr eated model rats with irreversible chronic renal disease per orally wi th 500 mg/kg bodyweight of PFD per day. The model rats were made by in travenous injection of anti-Thy-1 monoclonal antibody 1-22-3 at Ih fol lowing unilateral nephrectomy, which results in chronic progressive gl omerulosclerosis. 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 in take was observed between the two groups. The remnant kidney was signi ficantly (P<0.05) heavier in C (2.11 +/- 0.15g) 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 hypertroph y. On day 42, proteinuria in P (124.3 +/- 31.9 mg/day) was significant ly lower than in C (214.6 +/- 8.1 mg/day), and P maintained significan tly better renal function than C as judged by serum urea nitrogen and creatinine levels. Mean matrix score was less in P (178 +/- 17) than i n 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 imm unohistochemistry (e.g. ED-1, OX8, TGF-beta alpha-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.