Meta-analysis: Effectiveness of Drugs for Preventing Contrast-Induced Nephropathy

  1. Aine M. Kelly, MD, MS;
  2. Ben Dwamena, MD;
  3. Paul Cronin, MD, MS;
  4. Steven J. Bernstein, MD, MPH; and
  5. Ruth C. Carlos, MD, MS
  1. From the University of Michigan and Veteran Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.

    Abstract

    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 × 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% CI, 0.44 to 0.88]) and theophylline (relative risk, 0.49 [CI, 0.23 to 1.06]) reduced the risk for contrast-induced nephropathy more than saline alone, whereas furosemide increased it (relative risk, 3.27 [CI, 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.

    Article and Author Information

    • Grant Support: Funded in part by the National Institutes of Health and the National Cancer Institute (grant 1 K07 CA108664 01A1) and the General Electric–Association of University Radiologists Radiology Research Academic Fellowship.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Aine M. Kelly, MD, MS, Department of Radiology, Division of Cardiothoracic Radiology, University of Michigan Hospitals, B1 132K Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109; e-mail, ainekell{at}med.umich.edu.

    • Current Author Addresses: Drs. Kelly and Cronin: Department of Radiology, Division of Cardiothoracic Imaging, University of Michigan, 1500 East Medical Center, Ann Arbor, MI 48109.

    • Dr. Dwamena: Division of Nuclear Medicine, University of Michigan, 1500 East Medical Center, Ann Arbor, MI 48109.

    • Dr. Bernstein: Department of Internal Medicine, University of Michigan, 1500 East Medical Center, Ann Arbor, MI 48109.

    • Dr. Carlos: Department of Radiology, Division of Magnetic Resonance Imaging, University of Michigan, 1500 East Medical Center, Ann Arbor, MI 48109.

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