Reduction of renal interstitial fibrosis and protection of renal function by pentoxifylline in chronic partial ureteral obstruction

Abstract

Tubulointerstitial fibrosis (TIF) is a hallmark of progressive renal disease from diverse etiologies and is a reliable marker of disease severity. In the present study, we examined whether pentoxifylline (PTF), a phosphodiesterase inhibitor, reduced TIF in a rat model of chronic partial ureteral obstruction (PUO). Male Sprague‐Dawley rats underwent removal of the right kidney and diversion of the left ureter into the psoas muscle which was split and reapproximated to produce retroperitoneal fibrosis and PUO. Studies were performed in sham‐PUO rats and 30‐day PUO rats receiving PTF (400 mg/liter in drinking water) or no PTF (control) (4 rats in each group). Intravenous pyelogram showed hydronephrosis in PUO rats. Western blot showed that the α‐smooth muscle actin expression (an indicator of renal fibrosis) in the medulla was 1.16±0.40 (densitometry unit) in control rats, significantly greater than 0.37±0.03 in PTF‐treated rats. Histological examination revealed less TIF in kidneys in PTF‐treated rats than in control rats. GFR in PTF‐treated rats was 0.89±0.04 ml/min/g, greater than 0.24±0.16 ml/min/g in control rats (p<0.001). In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.