Protective effect of a platelet-activating factor antagonist (WEB-2086) in postischemic renal failure.

The purpose of this study was to evaluate the renoprotective effect of a specific platelet-activating factor antagonist (WEB-2086) in an experimental model of normothermic renal ischemia. Twenty New Zealand white rabbits were studied for 2 days before and 24 hours after a 60-minute period of renal ischemia induced by bilateral clamping of the renal arteries. The animals were divided into two groups: a control group (group A; n = 10) and a treated group (group B; n = 10). In group A the urinary flow rate decreased significantly (from 0.098 +/- 0.008 ml/min to 0.029 +/- 0.005 ml/min) (p < 0.001) and there was a significant reduction in creatinine clearance (from 11.4 +/- 1.2 ml/min to 3.4 +/- 1.1 ml/min) (p < 0.001). In group B no significant changes were observed, although the urinary flow rate increased even in the postischemic period (from 0.09 +/- 0.008 ml/min to 0.11 +/- 0.02 ml/min). Microcirculatory cortical flow showed a postischemic reduction in both groups, although it was most significant in the control group (group A = 43.7%, group B = 71.5%; p < 0.001). Histologic study showed mild damage with patchy tubular necrosis in both groups, although this injury was less severe in the treated group. The results suggest that the preoperative administration of WEB-2086 produces a potent diuretic effect with significant attenuation of postischemic acute renal failure.