title: Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism.
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 micromol/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 > or =0.5 mg/dL (44 micromol/L) or > 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 micromol/L)] than in the placebo group [0.4 +/- 0.6 mg/dL (33.6 +/- 55.1 micromol/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.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. wang0016@mc.duke.edu
authors.forename: A
authors.initials: A
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Holcslaw
authors.forename: T M
authors.initials: TM
authors.lastname: Bashore
authors.forename: M I
authors.initials: MI
authors.lastname: Freed
authors.forename: D
authors.initials: D
authors.lastname: Miller
authors.forename: M R
authors.initials: MR
authors.lastname: Rudnick
authors.forename: H
authors.initials: H
authors.lastname: Szerlip
authors.forename: M D
authors.initials: MD
authors.lastname: Thames
authors.forename: C J
authors.initials: CJ
authors.lastname: Davidson
authors.forename: N
authors.initials: N
authors.lastname: Shusterman
authors.forename: S J
authors.initials: SJ
authors.lastname: Schwab
mesh_terms: D000368:Aged; D003287:Contrast Media / Q000506:poisoning*; D017023:Coronary Angiography; D003404:Creatinine / Q000097:blood; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007189:Indans / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000097:blood / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012965:Sodium Chloride / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D003287:Contrast Media; D065128:Endothelin Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D012965:Sodium Chloride; D003404:Creatinine