Meta-analysis: Effectiveness of drugs for preventing contrast-induced nephropathy

Background: N-Acetylcysteine, theophylline, and other agents have shown inconsistent results in reducing contrast-induced nephropathy. Purpose: To determine the effect of these agents on preventing nephropathy. Data Sources: Relevant randomized, controlled trials were identified by computerized searches in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases (up to November 2006). Databases were searched for studies in English, Spanish, French, Italian, and German. Study Selection: Randomized, controlled trials that administered N-acetylcysteine, theophylline, fenoldopam, dopamine, iloprost, statin, furosemide, or mannitol to a treatment group; used intravenous iodinated contrast; defined contrast-induced nephropathy explicitly; and reported sufficient data to construct a 2 x 2 table of the primary effect measure. Data Extraction: Abstracted information included patient characteristics, type of contrast media and dose, periprocedural hydration, definition of contrast-induced nephropathy, and prophylactic agent dose and route. Data Synthesis: In the 41 studies included, N-acetylcysteine (relative risk, 0.62 [95% Cl, 0.44 to 0.881) and theophylline (relative risk, 0.49 [Cl, 0.23 to 1.061) reduced the risk for contrast-induced nephropathy more than saline alone, whereas furosemide increased it (relative risk, 3.27 [Cl, 1.48 to 7.26]). The remaining agents did not significantly affect risk. Significant subgroup heterogeneity was present only for N-acetylcysteine. No publication bias was discerned. Limitations: All trials evaluated the surrogate end point of contrast-induced nephropathy as the primary outcome. The lack of a statistically significant renoprotective effect of theophylline may result from insufficient data or study heterogeneity. True study quality remains uncertain. Conclusion: N-Acetylcysteine is more renoprotective than hydration alone. Theophylline may also reduce risk for contrast-induced nephropathy, although the detected association was not significant. Our data support the administration of N-acetylcysteine prophylaxis, particularly in high-risk patients, given its low cost, availability, and few side effects.