John Eng, MD; Renee F. Wilson, MS; Rathan M. Subramaniam, MD, PhD, MPH; Allen Zhang, BS; Catalina Suarez-Cuervo, MD; Sharon Turban, MD, MHS; Michael J. Choi, MD; Cheryl Sherrod, MD, MPH; Susan Hutfless, PhD; Emmanuel E. Iyoha, MBChB, MPH; Eric B. Bass, MD, MPH
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Grant Support: By the Agency for Healthcare Research and Quality (contract 290-2012-00007I).
Disclosures: Dr. Eng reports a contract from the Agency for Healthcare Research and Quality during the conduct of the study. Ms. Wilson reports grants from the Agency for Healthcare Research and Quality during the conduct of the study. Dr. Subramaniam reports grants from the Agency for Healthcare Research and Quality during the conduct of the study and a grant from Bayer Health Care and consulting fees from Philips Healthcare outside the submitted work. Dr. Choi reports that he is President Elect of the National Kidney Foundation. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1402.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Eng (e-mail, email@example.com).
Requests for Single Reprints: John Eng, MD, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Eng: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287.
Ms. Wilson, Mr. Zhang, Mr. Iyoha, and Dr. Bass: Johns Hopkins University, Evidence-based Practice Center, 624 North Broadway, Suite 648, Baltimore, MD 21205.
Dr. Subramaniam: Johns Hopkins Outpatient Center, 601 North Caroline Street, Room 3235, Baltimore, MD 21287.
Dr. Suarez-Cuervo: 112 Affirmed Court, Elizabethtown, KY 42701.
Drs. Turban and Choi: Johns Hopkins University School of Medicine, Department of Medicine, Division of Nephrology, 1830 East Monument Street, Suite 416, Baltimore, MD 21287.
Dr. Sherrod: PO Box 1582, Cordova, TN 38088.
Dr. Hutfless: Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Blalock Building, Room 449, 600 North Wolfe Street, Baltimore, MD 21287.
Author Contributions: Conception and design: J. Eng, R.F. Wilson, R.M. Subramaniam, S. Turban, E.B. Bass.
Analysis and interpretation of the data: J. Eng, R.F. Wilson, R.M. Subramaniam, A. Zhang, C. Suarez-Cuervo, S. Turban, M.J. Choi, C. Sherrod, S. Hutfless, E.B. Bass.
Drafting of the article: J. Eng, R.F. Wilson, R.M. Subramaniam, M.J. Choi.
Critical revision of the article for important intellectual content: J. Eng, R.F. Wilson, R.M. Subramaniam, C. Suarez-Cuervo, S. Turban, M.J. Choi, S. Hutfless, E.B. Bass.
Final approval of the article: J. Eng, R.F. Wilson, R.M. Subramaniam, A. Zhang, C. Suarez-Cuervo, S. Turban, M.J. Choi, C. Sherrod, S. Hutfless, E.E. Iyoha, E.B. Bass.
Statistical expertise: J. Eng, E.B. Bass.
Obtaining of funding: E.B. Bass.
Administrative, technical, or logistic support: R.F. Wilson, A. Zhang, C. Sherrod, E.B. Bass.
Collection and assembly of data: J. Eng, R.F. Wilson, R.M. Subramaniam, A. Zhang, C. Suarez-Cuervo, S. Turban, M.J. Choi, C. Sherrod.
Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN).
To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures.
PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015.
Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging.
Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results.
None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk.
Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment.
No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance.
Agency for Healthcare Research and Quality.
Appendix Table 1. Search Strategy
Summary of evidence search and selection.
* Sum of reasons for exclusion exceeds 443 because reviewers were not required to agree on the reason.
Appendix Table 2. Study Characteristics
Appendix Table 3. Risk of Bias for RCTs Comparing LOCMs*
Appendix Table 4. Risk of Bias for RCTs Comparing Iodixanol and LOCMs*
Table 1. Results of Studies Comparing LOCM
Table 2. Grading Strength of Evidence
Graphical summary of meta-analysis of randomized, controlled trials comparing iodixanol and LOCM with contrast-induced nephropathy as the primary outcome.
The solid vertical line represents the null hypothesis (relative risk equal to 1), and the dashed vertical line represents the pooled estimate from the meta-analysis. Studies are shown in reverse chronologic order, grouped by route of administration. LOCM = low-osmolar contrast media, RR = relative risk.
Appendix Table 5. Results of Studies Comparing Iodixanol With LOCM
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Eng J, Wilson RF, Subramaniam RM, et al. Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 2 February 2016]164:417–424. doi: 10.7326/M15-1402
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Published: Ann Intern Med. 2016;164(6):417-424.
Published at www.annals.org on 2 February 2016
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