Effects of pentoxifylline in experimental acute renal failure

The beneficial effects of post-insult administration of pentoxifylline, a novel hemorheologic agent experimentally studied in various ischemic diseases, were evaluated in two models of acute renal failure (ARF): direct nephrotoxicity (mercuric chloride 4 mg/kg via femoral vein) and hemoglobinuria (glycerol 10 ml/kg i.m.). Glomerular filtration rate (GFR) was estimated at baseline and following drug administration by creatinine clearances; tubular function was assessed by renal fractional and absolute electrolyte excretions. The incidence of mortality was decreased with a single dose of pentoxifylline 45 mg/kg (21.4%) compared to control rats (71.4%) 48 hours following induction of ARF with mercuric chloride. Although GFR and renal electrolyte excretion were significantly greater in rats given pentoxifylline compared to saline, the magnitude of difference was minimal. A return to baseline GFR was observed in the glycerol group administered a single i.p. dose of pentoxifylline 45 mg/kg (100.8 +/- 54.8%) compared to saline controls (45.6 +/- 22.7%; P less than 0.05). No differences in renal electrolyte excretion or mortality were observed in this model. Taken together, these data suggest that pentoxifylline, administered shortly after the initiation of ARF, exerts an ameliorative effect on the course and mortality of experimental ARF. The mechanism of amelioration most likely involves the stimulation of renal vasodilator prostaglandins as well as prevention of vascular congestion.