Effects of OKY 046, a thromboxane-synthase inhibitor, on renal function in nonazotemic cirrhotic patients with ascites

Abstract

To assess the possible role of increased renal thromboxane A2 (TXA2) synthesis in nonazotemic patients with cirrhosis and ascites and to establish the potential beneficial effect of inhibitors of renal TXA2 production in this clinical setting, we administered OKY 046, a selective TXA2 synthase inhibitor, 200 mg t.i.d for 5 days, to 9 nonazotemic cirrhotic patients with ascites and avid sodium retention. OKY 046 inhibited platelet TXA2 production, as expressed by serum thromboxane B2 (TXB2) concentration, by ~85% (p < 0.001 vs. baseline values) and reduced urinary TXB2 excretion by 72% (p < 0.01). A significant increase of ~19% in inulin clearance was observed during the treatment (from 61.0 ± 8.42 to 72.7 ± 7.45 ml/min, p < 0.05), whereas renal blood flow was unchanged (from 408.50 ± 19.97 to 424.50 ± 30.84 ml/min). Drug administration did not affect positive sodium balance [sodium excretion was 4.67 ± 1.22 mEq/day before drug administration and 6.26 ± 1.05 mEq/day during drug administration (on day 7)], plasma renin activity, plasma aldosterone concentration, or the urinary excretion of prostaglandin E2, 6-keto prostaglandin F1α, or prostaglandin F2α. These results suggest that renal TXA2 synthesis contributes to the regulation of renal hemodynamics in nonazotemic cirrhotic patients with ascites and avid sodium retention, but it does not seem to affect sodium balance.