Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism

Andrew Wang*, Terry Holcslaw, Thomas M. Bashore, Martin I. Freed, Diane Miller, Michael R. Rudnick, Harold Szerlip, Marc D. Thames, Charles J. Davidson, Neil Shusterman, Steven J. Schwab

*Corresponding author for this work

Research output: Contribution to journalArticle

210 Scopus citations

Abstract

Background. Endothelin is a potent vasoconstrictor that has been implicated in the pathogenesis of radiocontrast nephrotoxicity. Endothelin antagonists may reduce the renal hemodynamic abnormalities following radiocontrast administration. 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 μmol/L)] and undergoing cardiac angiography were randomized to receive either a mixed endothelin A and B receptor antagonist, SB 290670, or placebo. All patients received intravenous hydration with 0.45% saline before and after radiocontrast administration. Serum creatinine concentrations were measured at baseline, 24 hours, 48 hours, and 3 to 5 days after radiocontrast administration. The primary end point was the mean change in serum creatinine concentration from baseline at 48 hours; the secondary end point was the incidence of radiocontrast nephrotoxicity, defined as an increase in serum creatinine of ≥0.5 mg/dL (44 μmol/L) or ≥25% from baseline within 48 hours of radiocontrast administration. Results. The mean increase in serum creatinine 48 hours after angiography was higher in the SB 209670 group [0.7 ± 0.7 mg/dL (63.5 ± 58.6 μmol/L)] than in the placebo group [0.4 ± 0.6 mg/dL (33.6 ± 55.1 μmol/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 negative effect of SB 209670 was apparent in both diabetic and nondiabetic patients. 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 undergoing cardiac angiography, endothelin receptor antagonism with SB 209670 and intravenous hydration exacerbate radiocontrast nephrotoxicity compared with hydration alone.

Original languageEnglish (US)
Pages (from-to)1675-1680
Number of pages6
JournalKidney international
Volume57
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Cardiac angiography
  • Endothelin
  • Nephrotoxic radiocontrast medium
  • Receptor
  • Renal failure

ASJC Scopus subject areas

  • Nephrology

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    Wang, A., Holcslaw, T., Bashore, T. M., Freed, M. I., Miller, D., Rudnick, M. R., Szerlip, H., Thames, M. D., Davidson, C. J., Shusterman, N., & Schwab, S. J. (2000). Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism. Kidney international, 57(4), 1675-1680. https://doi.org/10.1046/j.1523-1755.2000.00012.x