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REVIEW

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

Aine M. Kelly, MD, MS; Ben Dwamena, MD; Paul Cronin, MD, MS; Steven J. Bernstein, MD, MPH; and Ruth C. Carlos, MD, MS

19 February 2008 | Volume 148 Issue 4 | Pages 284-294

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% 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.

Editors' Notes Context Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients. Clinicians use a variety of contrast agents to reduce the risk for contrast-induced nephropathy, including N-acetylcysteine, theophylline, fenoldopam, dopamine, furosemide, mannitol, and bicarbonate. Contribution Although all of the agents included in this analysis reduced the risk for contrast-induced nephropathy, this meta-analysis of 33 trials involving 3622 patients found the strongest evidence for the effectiveness of N-acetylcysteine, mannitol, and theophylline when compared with periprocedural hydration alone. Caution Available studies examined laboratory end points (such as an increase in serum creatinine levels) rather than clinical end points (such as dialysis or death). —The Editors

 

Author and Article Information

From the University of Michigan and Veteran Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan.

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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