Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism

Background. Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonist s may reduce the renal hemodynamic abnormalities following radiocontrast ad ministration. Methods. One hundred fifty-eight patients with chronic renal insufficiency [mean serum creatinine +/- SD = 2.7 +/- 1.0 mg/dL (242.3 to +/- 92.8 mu mol /L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All p atients received intravenous hydration with 0.45% saline before and after r adiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast admini stration. The primary end point was the mean change in serum creatinine con centration from baseline at 48 hours; the secondary end point was the incid ence of radiocontrast nephrotoxicity, defined as an increase in serum creat inine of greater than or equal to 0.5 mg/dL (44 mu mol/L) or greater than o r equal to 25% from baseline within 48 hours of radiocontrast administratio n. Results. The mean increase in serum creatinine 48 hours after angiography w as higher in the SB 209670 group [0.7 +/- 0.7 mg/dL (63.5 +/- 58.6 mu mol/L )] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 mu mol/L), P = 0.002]. The incidence of radiocontrast nephrotoxicity was also higher in the SB 209670 group (56%) compared with placebo (29%, P = 0.002). This neg ative effect of SE 209670 was apparent in both diabetic and nondiabetic pat ients. Adverse effects, especially hypotension or decreased blood pressure, were more common in the SB 209670 group. Conclusions. In patients with chronic renal insufficiency who were undergoi ng cardiac angiography, endothelin receptor antagonism with SB 209670 and i ntravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.