Contrast-induced Nephropathy Comparative Effectiveness of Preventive Measures

OBJECTIVE: To evaluate the comparative effectiveness of interventions (intravenous [IV] fluids, N-acetylcysteine, sodium bicarbonate, and statins, among others) to reduce the risk of contrast-induced nephropathy (CIN), need for renal replacement therapy, mortality, cardiac complications, prolonged length of stay, and other adverse events after receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media (IOCM). DATA SOURCES: We searched for original published studies in MEDLINE(r), Embase(r), and the Cochrane Library through July 8, 2015. We also searched ClinicalTrials.gov and the Scopus database. METHODS: Two reviewers independently reviewed each article for eligibility. For each study, one reviewer extracted the data and a second reviewer verified the accuracy. Both reviewers assessed study quality. Together, the reviewers graded the strength of evidence (SOE) on preventing CIN and other adverse outcomes for the comparisons of interest. The team quantitatively pooled results of studies that were sufficiently similar using a random-effects model. We considered a 25-percent relative risk difference to be clinically important. RESULTS: We found 163 randomized controlled trials (RCTs) and 23 prospective studies of interventions to prevent CIN, including 67 RCTs comparing N-acetylcysteine with IV saline versus IV saline with or without a placebo; 28 RCTs comparing IV sodium bicarbonate versus IV saline; 7 RCTs comparing IV sodium bicarbonate versus N-acetylcysteine plus IV saline; 8 RCTs comparing a statin versus IV saline; 5 RCTs comparing a statin plus N-acetylcysteine versus N-acetylcysteine; 6 RCTs comparing statin versus statin, statin by dose, or statins plus other agents; 5 RCTs comparing an adenosine antagonist versus IV saline; 6 RCTs investigating hemodialysis or hemofiltration versus IV saline; 6 RCTs comparing ascorbic acid versus IV saline, and 3 RCTs comparing ascorbic acid to N-acetylcysteine. Although we found many studies investigating other interventions, the studies were too small and too few to support conclusions regarding the comparative effectiveness of those interventions. The studies were published between 1998 and 2015. The SOE was low that high-dose [>1,200 mg/day] N-acetylcysteine had a small clinically unimportant effect in preventing CIN when compared with IV saline (pooled risk ratio [RR], 0.78; 95% confidence interval [CI], 0.59 to 1.03); and the SOE was low that low-dose [d1,200 mg/day] N-acetylcysteine had a borderline clinically important effect in preventing CIN when compared with IV saline (RR, 0.75; 95% CI, 0.63 to 0.89). A sensitivity analysis suggests the effect was clinically important when N-acetylcysteine was given for LOCM (moderate SOE; RR, 0.69; 95% CI, 0.58 to 0.84), but not when it was given for IOCM (low SOE; RR, 1.12; 95% CI, 0.74 to 1.69). Another sensitivity analysis found that the RR estimates did not differ between IV and intra-arterial routes of administration of contrast media. The SOE was low that using a statin plus N-acetylcysteine was more effective than N-acetylcysteine alone in preventing CIN in patients receiving intra-arterial contrast media (RR, 0.52; 95% CI, 0.29 to 0.93), and the SOE was low for a clinically important difference that was not statistically significant when comparing a statin plus IV saline to IV saline alone (RR, 0.68; 95% CI, 0.39 to 1.20). The SOE was low that IV sodium bicarbonate did not differ from IV saline in the risk of CIN (RR, 0.93; 95% CI, 0.68 to 1.27). The SOE was low for a clinically important reduction in CIN that was not statistically significant when comparing IV sodium bicarbonate with IV saline in patients receiving LOCM (RR, 0.65; 95% CI, 0.33 to 1.25). The SOE was low for a clinically important reduction in CIN that was not statistically significant when comparing ascorbic acid with IV saline (RR, 0.72; 95% CI, 0.48 to 1.01). The SOE was low that use of hemodialysis versus IV saline to prevent CIN did not reduce the risk of CIN and may even be harmful (RR, 1.50; 95% CI, 0.56 to 4.04). CONCLUSIONS: The evidence shows a clinically important and statistically significant benefit in studies of three comparisons: low-dose N-acetylcysteine compared with IV saline, N-acetylcysteine compared with IV saline in patients receiving LOCM, and statins plus N-acetylcysteine compared with N-acetylcysteine alone in patients receiving intra-arterial contrast media. Future research is needed to determine whether statins can reduce CIN in patients receiving IV contrast media, and to further define specific contexts in which patients could benefit from use of N-acetylcysteine.