Systematic review of the impact of N-acetylcysteine on contrast nephropathy

Background. The efficacy of N-acetylcysteine (NAC) for preventing contrast nephropathy is uncertain. We performed a systematic review and meta-analysis to assess the efficacy of NAC for preventing contrast nephropathy after administration of intravenous contrast media. Methods. Data were obtained from searching MEDLINE (1969-2003) and EMBASE (1988-2003), Cochrane Controlled Clinical Trial Registry (2002, Volume 3), and conference proceedings. We considered all randomized studies that compared changes in renal function between groups that received and did not receive NAC. Studies in which the control group also received active therapy were excluded, although cointervention directed at both groups was permitted. Two reviewers independently extracted quantitative and qualitative data. Disagreements were resolved by consensus with the aid of a third party. Results. Fifteen studies with a total of 1776 patients satisfied inclusion and exclusion criteria. Contrast nephropathy was typically defined by an increase in serum creatinine of 0.5 mg/dL within 24 to 48 hours of contrast administration. The pooled random effect relative risk was 0.65 (0.43-1.00, P = 0.049), indicating that NAC significantly reduced the incidence of contrast nephropathy. However, the effect of NAC was not statistically significant in several prespecified subgroup analyses, and the results were not robust to the addition of hypothetical new or unidentified randomized trials. There was evidence of significant heterogeneity in NAC effect across studies (Q = 26.3, P = 0.02). Random effects meta-regression did not implicate identified differences in participant or study characteristics as responsible for the observed heterogeneity. Conclusion. NAC may reduce the incidence of acutely increased serum creatinine after administration of intravenous contrast, but this finding was of borderline statistical significance, and there was significant heterogeneity between trials. Before NAC becomes the standard of care for all patients receiving intravenous contrast, new randomized trials evaluating its effect on clinically relevant outcomes are required.