The relative renal safety of iodixanol compared with low-osmolar contrast media: a meta-analysis of randomized controlled trials.

OBJECTIVES We sought to compare the nephrotoxicity of the iso-osmolar contrast medium, iodixanol, to low-osmolar contrast media (LOCM). BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is a common cause of in-hospital renal failure. A prior meta-analysis suggested that iodixanol (Visipaque, GE Healthcare, Princeton, New Jersey) was associated with less CI-AKI than LOCM, but this study was limited by ascertainment bias and did not include the most recent randomized controlled trials. METHODS We searched Medline, Embase, ISI Web of Knowledge, Google Scholar, Current Contents, and International Pharmaceutical Abstracts databases, and the Cochrane Central Register of Controlled Trials from 1980 to November 30, 2008, for randomized controlled trials that compared the incidence of CI-AKI with either iodixanol or LOCM. Random-effects models were used to calculate summary risk ratios (RR) for CI-AKI, need for hemodialysis, and death. RESULTS A total of 16 trials including 2,763 subjects were pooled. There was no significant difference in the incidence of CI-AKI in the iodixanol group than in the LOCM group overall (summary RR: 0.79, 95% confidence interval [CI]: 0.56 to 1.12, p = 0.19). There was no significant difference in the rates of post-procedure hemodialysis or death. There was a reduction in CI-AKI when iodixanol was compared with ioxaglate (RR: 0.58, 95% CI: 0.37 to 0.92; p = 0.022) and iohexol (RR: 0.19, 95% CI: 0.07 to 0.56; p = 0.002), but no difference when compared with iopamidol (RR: 1.20, 95% CI: 0.66 to 2.18; p = 0.55), iopromide (RR: 0.93, 95% CI: 0.47 to 1.85; p = 0.84), or ioversol (RR: 0.92, 95% CI: 0.60 to 1.39; p = 0.68). CONCLUSIONS This meta-analysis including 2,763 subjects suggests that iodixanol, when compared with LOCM overall, is not associated with less CI-AKI. The relative renal safety of LOCM compared with iodixanol may vary based on the specific type of LOCM.

[1]  H. Rusinek,et al.  High-dose administration of nonionic contrast media: a retrospective review. , 1996, Radiology.

[2]  N. Chalmers,et al.  Comparison of iodixanol and iohexol in renal impairment. , 1999, The British journal of radiology.

[3]  W. Laskey,et al.  Nephrotoxicity of iodixanol versus ioversol in patients with chronic kidney disease: the Visipaque Angiography/Interventions with Laboratory Outcomes in Renal Insufficiency (VALOR) Trial. , 2008, American heart journal.

[4]  R. Erbel,et al.  Nephrotoxicity of iso-osmolar versus low-osmolar contrast media is equal in low risk patients. , 2006, Clinical nephrology.

[5]  P. Parfrey,et al.  Contrast nephropathy in patients with impaired renal function: high versus low osmolar media. , 1992, Kidney international.

[6]  E. V. van Beek,et al.  The PREDICT study: a randomized double-blind comparison of contrast-induced nephropathy after low- or isoosmolar contrast agent exposure. , 2008, AJR. American journal of roentgenology.

[7]  B. Barrett,et al.  Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. , 1993, Radiology.

[8]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

[9]  K. Endresen,et al.  Iodixanol in cardioangiography in patients with coronary artery disease. Tolerability, cardiac and renal effects. , 1993, Acta radiologica.

[10]  H. Thomsen,et al.  The ACTIVE Trial: Comparison of the Effects on Renal Function of Iomeprol-400 and Iodixanol-320 in Patients With Chronic Kidney Disease Undergoing Abdominal Computed Tomography , 2008, Investigative radiology.

[11]  W. Bautz,et al.  Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low-osmolar contrast media: meta-analysis of randomized controlled trials. , 2009, Radiology.

[12]  R. Bersin,et al.  Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. , 2004, JAMA.

[13]  Kirk N. Garratt,et al.  Incidence and Prognostic Importance of Acute Renal Failure After Percutaneous Coronary Intervention , 2002, Circulation.

[14]  M. Rosenberg,et al.  THE FILE‐DRAWER PROBLEM REVISITED: A GENERAL WEIGHTED METHOD FOR CALCULATING FAIL‐SAFE NUMBERS IN META‐ANALYSIS , 2005, Evolution; international journal of organic evolution.

[15]  Gilles Soulez,et al.  Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease Undergoing Computed Tomography: A Double-Blind Comparison of Iodixanol and Iopamidol , 2006, Investigative radiology.

[16]  A. Colombo,et al.  Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): A Randomized Comparison of 3 Preventive Strategies , 2007, Circulation.

[17]  E. Cantor,et al.  The relative renal safety of iodixanol compared with low-osmolar contrast media. , 2009, JACC. Cardiovascular interventions.

[18]  W. Heindel,et al.  Whole-body imaging of oncologic patients using 16-channel PET-CT , 2008, Nuklearmedizin.

[19]  M. Rich,et al.  Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. , 1990, Archives of internal medicine.

[20]  U. Schoepf,et al.  Iso-osmolality versus low-osmolality iodinated contrast medium at intravenous contrast-enhanced CT: effect on kidney function. , 2008, Radiology.

[21]  Brady T. West,et al.  Linear Mixed Models: A Practical Guide Using Statistical Software , 2006 .

[22]  B. Bolstad,et al.  Iodixanol and ioxaglate in cardioangiography: a double-blind randomized phase III study. , 1993, Clinical radiology.

[23]  J. Brinker,et al.  A meta-analysis of the renal safety of isosmolar iodixanol compared with low-osmolar contrast media. , 2006, Journal of the American College of Cardiology.

[24]  Sven-Göran Fransson,et al.  Nephrotoxic effects in high-risk patients undergoing angiography. , 2003, The New England journal of medicine.

[25]  P. Persson,et al.  Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media. , 2006, Kidney international.

[26]  M. Cova,et al.  Effects of a dimeric vs a monomeric nonionic contrast medium on renal function in patients with mild to moderate renal insufficiency: a double-blind, randomized clinical trial , 1998, European Radiology.

[27]  E. Topol,et al.  Double jeopardy of renal insufficiency and anemia in patients undergoing percutaneous coronary interventions. , 2004, The American journal of cardiology.

[28]  K. Shojania,et al.  Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. , 2004, The American journal of medicine.

[29]  H. Gurm,et al.  Current role of sodium bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: a meta-analysis. , 2008, American heart journal.

[30]  Samin K. Sharma,et al.  Cardiac Angiography in Renally Impaired Patients (CARE) Study: A Randomized Double-Blind Trial of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease , 2007, Circulation.

[31]  P. Persson,et al.  Pathophysiology of contrast medium-induced nephropathy. , 2005, Kidney international.

[32]  P. Aspelin.  [Reduced risk of nepropathy with isoosmolar contrast media]. , 2003, Lakartidningen.

[33]  B. Bolstad,et al.  Iodixanol in Cardioangiography , 1994 .

[34]  Lisa A. Weissfeld,et al.  An assessment of the use of the continuity correction for sparse data in meta-analysis , 1996 .

[35]  R. Orwin.  A fail-safe N for effect size in meta-analysis. , 1983 .

[36]  M. Lins,et al.  Hypoxic renal tissue damage by endothelin-mediated arterial vasoconstriction during radioangiography in man. , 1998, Advances in experimental medicine and biology.

[37]  Deepak L. Bhatt,et al.  Renal failure after percutaneous coronary intervention is associated with high mortality , 2005, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[38]  Young‐Bae Park,et al.  Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial. , 2006, Journal of the American College of Cardiology.

[39]  B. Rutherford,et al.  High-dose contrast agent administration during complex coronary angioplasty. , 1990, American heart journal.

[40]  M. Egger,et al.  The hazards of scoring the quality of clinical trials for meta-analysis. , 1999, JAMA.

[41]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[42]  Michele Meschi,et al.  Contrast nephropathy: isosmolar and low-osmolar contrast media. , 2007, Journal of the American College of Cardiology.