CLINICAL RESEARCH: INVASIVE CARDIOLOGY
A Meta-Analysis of the Renal Safety of Isosmolar Iodixanol Compared With Low-Osmolar Contrast Media
Peter A. McCullough, MD, MPH, FACC*,*,
Michel E. Bertrand, MD, FACC ,
Jeffrey A. Brinker, MD, FACC and
Fulvio Stacul, MD
* Department of Medicine, Divisions of Cardiology and Preventive Medicine, William Beaumont Hospital, Royal Oak, Michigan
Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Division of Cardiology, University of Lille, Lille, France
Institute of Radiology, University of Trieste, Trieste, Italy
Manuscript received October 3, 2005;
revised manuscript received February 22, 2006,
accepted February 28, 2006.
* Reprint requests and correspondence: Dr. Peter A. McCullough, Divisions of Cardiology and Preventive Medicine, William Beaumont Hospital, 4949 Coolidge Highway, Royal Oak, Michigan 48073. (Email: pmccullough{at}beaumont.edu).
OBJECTIVES: We sought to compare the nephrotoxicity of isosmolar contrast medium (IOCM) iodixanol with low-osmolar contrast media (LOCM) and to identify predictors of contrast-induced nephropathy (CIN).
BACKGROUND: Contrast-induced nephropathy is a serious complication of diagnostic and interventional procedures.
METHODS: Pooled individual patient data (n = 2,727) from 16 double-blind, randomized, controlled trials in which patients received either intra-arterial IOCM iodixanol (n = 1,382) or LOCM (n = 1,345) were included. Patients were stratified according to chronic kidney disease (CKD), diabetes mellitus (DM), or both. Outcome measures were the maximum increase in serum creatinine (Cr) over baseline and the incidence of postprocedural CIN.
RESULTS: The maximum Cr increase within 3 days after contrast medium (CM) administration was significantly smaller in the iodixanol group compared with the LOCM group (0.06 mg/dl vs. 0.10 mg/dl, p < 0.001), particularly in patients with CKD (0.07 mg/dl vs. 0.16 mg/dl, p = 0.004) and CKD + DM (0.10 mg/dl vs. 0.33 mg/dl, p = 0.003). Contrast-induced nephropathy, defined as an increase in Cr  0.50 mg/dl within 3 days after CM administration, occurred less frequently in the iodixanol group than in the LOCM group in all patients (1.4% vs. 3.5%, p < 0.001), in CKD patients (2.8% vs. 8.4%, p = 0.001), and in CKD + DM patients (3.5% vs. 15.5%, p = 0.003). Independent predictors of CIN included CKD, CKD + DM, and use of LOCM.
CONCLUSIONS: This meta-analysis of pooled data from 2,727 patients indicates that use of the IOCM iodixanol is associated with smaller rises in Cr and lower rates of CIN than LOCM, especially in patients with CKD or CKD + DM.
|
Abbreviations and Acronyms
| | CI = confidence interval | | CIN = contrast-induced nephropathy | | CKD = chronic kidney disease | | CM = contrast media | | Cr = creatinine | | DM = diabetes mellitus | | HOCM = high-osmolar contrast media | | IOCM = isosmolar contrast media | | LOCM = low-osmolar contrast media |
|
This article has been cited by other articles:
|
|
|
|
 
J. Wi, Y.-G. Ko, J.-S. Kim, B.-K. Kim, D. Choi, J.-W. Ha, M.-K. Hong, and Y. Jang
Impact of contrast-induced acute kidney injury with transient or persistent renal dysfunction on long-term outcomes of patients with acute myocardial infarction undergoing percutaneous coronary intervention
Heart,
November 1, 2011;
97(21):
1753 - 1757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Maioli, A. Toso, M. Leoncini, C. Micheletti, and F. Bellandi
Effects of Hydration in Contrast-Induced Acute Kidney Injury After Primary Angioplasty: A Randomized, Controlled Trial
Circ Cardiovasc Interv,
October 1, 2011;
4(5):
456 - 462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Konishi, S. Matsushita, K. Hyodo, F. Sato, Y. Hiramatsu, and Y. Sakakibara
Reducing the Dose of Contrast Medium in Angiography by Use of a Highly Sensitive Receiver and Synchrotron Radiation System
Am. J. Roentgenol.,
September 1, 2011;
197(3):
W508 - W513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Wright, J. L. Anderson, C. D. Adams, C. R. Bridges, D. E. Casey Jr, S. M. Ettinger, F. M. Fesmire, T. G. Ganiats, H. Jneid, A. M. Lincoff, et al.
2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J. Am. Coll. Cardiol.,
May 10, 2011;
57(19):
e215 - e367.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al.
2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation,
May 10, 2011;
123(18):
e426 - e579.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Serafin, M. Karolkiewicz, M. Gruszka, P. Strozecki, W. Lasek, G. Odrowaz-Sypniewska, J. Manitius, and W. Beuth
High incidence of nephropathy in neurosurgical patients after intra-arterial administration of low-osmolar and iso-osmolar contrast media
Acta Radiol,
May 1, 2011;
52(4):
422 - 429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Chartrand-Lefebvre, C. S. White, S. Bhalla, W. W. Mayo-Smith, J. Prenovault, K. H. Vydareny, J. A. Soto, O. S. Ozkan, A. R. Chughtai, and G. Soulez
Comparison of the Effect of Low- and Iso-Osmolar Contrast Agents on Heart Rate during Chest CT Angiography: Results of a Prospective Randomized Multicenter Study
Radiology,
March 1, 2011;
258(3):
930 - 937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ishibashi, M. Yamauchi, H. Musha, T. Mikami, K. Kawasaki, and F. Miyake
Impact of Contrast-Induced Nephropathy and Cardiovascular Events by Serum Cystatin C in Renal Insufficiency Patients Undergoing Cardiac Catheterization
Angiology,
November 1, 2010;
61(8):
724 - 730.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. M. From, F. J. Al Badarin, F. S. McDonald, B. J. Bartholmai, S. S. Cha, and C. S. Rihal
Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy: Meta-analysis of Randomized, Controlled Trials
Circ Cardiovasc Interv,
August 1, 2010;
3(4):
351 - 358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Brochard, F. Abroug, M. Brenner, A. F. Broccard, R. L. Danner, M. Ferrer, F. Laghi, S. Magder, L. Papazian, P. Pelosi, et al.
An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: An International Consensus Conference in Intensive Care Medicine
Am. J. Respir. Crit. Care Med.,
May 15, 2010;
181(10):
1128 - 1155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Politi, F. Sgura, R. Rossi, D. Monopoli, E. Guerri, C. Leuzzi, F. Bursi, G. M. Sangiorgi, and M. G. Modena
A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up
Heart,
May 1, 2010;
96(9):
662 - 667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Byrne, G. Laarman, and P. MacCarthy
Chapter 7 Routine management after percutaneous coronary intervention
Oxford Textbook of Interventional Cardiology,
January 1, 2010;
1(1):
med-9780199569083-chapter - med-9780199569083-chapter.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F. G. Kushner, M. Hand, S. C. Smith Jr, S. B. King III, J. L. Anderson, E. M. Antman, S. R. Bailey, E. R. Bates, J. C. Blankenship, D. E. Casey Jr, et al.
2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J. Am. Coll. Cardiol.,
December 1, 2009;
54(23):
2205 - 2241.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. G. Kushner, M. Hand, S. C. Smith Jr, S. B. King III, J. L. Anderson, E. M. Antman, S. R. Bailey, E. R. Bates, J. C. Blankenship, D. E. Casey Jr, et al.
2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Circulation,
December 1, 2009;
120(22):
2271 - 2306.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Ferrario, M. T. Barone, G. Landoni, A. Genderini, M. Heidemperger, M. Trezzi, E. Piccaluga, P. Danna, and D. Scorza
Acetylcysteine and non-ionic isosmolar contrast-induced nephropathy--a randomized controlled study
Nephrol. Dial. Transplant.,
October 1, 2009;
24(10):
3103 - 3107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wessely, T. Koppara, C. Bradaric, M. Vorpahl, S. Braun, S. Schulz, J. Mehilli, A. Schomig, A. Kastrati, and for the Contrast Media and Nephrotoxicity Followin
Choice of Contrast Medium in Patients With Impaired Renal Function Undergoing Percutaneous Coronary Intervention
Circ Cardiovasc Interv,
October 1, 2009;
2(5):
430 - 437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Reed, P. Meier, U. U. Tamhane, K. B. Welch, M. Moscucci, and H. S. Gurm
The Relative Renal Safety of Iodixanol Compared With Low-Osmolar Contrast Media: A Meta-Analysis of Randomized Controlled Trials
J. Am. Coll. Cardiol. Intv.,
July 1, 2009;
2(7):
645 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Palevsky
Defining Contrast-Induced Nephropathy
Clin. J. Am. Soc. Nephrol.,
July 1, 2009;
4(7):
1151 - 1153.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. Ellis and R. H. Cohan
Reducing the Risk of Contrast-Induced Nephropathy: A Perspective on the Controversies
Am. J. Roentgenol.,
June 1, 2009;
192(6):
1544 - 1549.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Treitl, H. Rupprecht, S. Wirth, M. Korner, M. Reiser, and J. Rieger
Assessment of renal vasoconstriction in vivo after intra-arterial administration of the isosmotic contrast medium iodixanol compared to the low-osmotic contrast medium iopamidol
Nephrol. Dial. Transplant.,
May 1, 2009;
24(5):
1478 - 1485.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mehran, E. Nikolsky, A. J. Kirtane, A. Caixeta, S. C. Wong, P. S. Teirstein, W. E. Downey, W. B. Batchelor, P. J. Casterella, Y.-H. Kim, et al.
Ionic Low-Osmolar Versus Nonionic Iso-Osmolar Contrast Media to Obviate Worsening Nephropathy After Angioplasty in Chronic Renal Failure Patients: The ICON (Ionic versus non-ionic Contrast to Obviate worsening Nephropathy after angioplasty in chronic renal failure patients) Study
J. Am. Coll. Cardiol. Intv.,
May 1, 2009;
2(5):
415 - 421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Bruce, A. Djamali, K. Shinki, S. J. Michel, J. P. Fine, and M. A. Pozniak
Background Fluctuation of Kidney Function Versus Contrast-Induced Nephrotoxicity
Am. J. Roentgenol.,
March 1, 2009;
192(3):
711 - 718.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Heinrich, L. Haberle, V. Muller, W. Bautz, and M. Uder
Nephrotoxicity of Iso-osmolar Iodixanol Compared with Nonionic Low-osmolar Contrast Media: Meta-analysis of Randomized Controlled Trials1
Radiology,
January 1, 2009;
250(1):
68 - 86.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lameire, W. Van Biesen, E. Hoste, and R. Vanholder
The prevention of acute kidney injury: an in-depth narrative review Part 1: volume resuscitation and avoidance of drug- and nephrotoxin-induced AKI
Clinical Kidney Journal,
December 1, 2008;
1(6):
392 - 402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Langner, S. Stumpe, M. Kirsch, M. Petrik, and N. Hosten
No Increased Risk for Contrast-Induced Nephropathy after Multiple CT Perfusion Studies of the Brain with a Nonionic, Dimeric, Iso-Osmolal Contrast Medium
AJNR Am. J. Neuroradiol.,
September 1, 2008;
29(8):
1525 - 1529.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Weisbord, M. K. Mor, A. L. Resnick, K. C. Hartwig, P. M. Palevsky, and M. J. Fine
Incidence and Outcomes of Contrast-Induced AKI Following Computed Tomography
Clin. J. Am. Soc. Nephrol.,
September 1, 2008;
3(5):
1274 - 1281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Maioli, A. Toso, M. Leoncini, M. Gallopin, D. Tedeschi, C. Micheletti, and F. Bellandi
Sodium Bicarbonate Versus Saline for the Prevention of Contrast-Induced Nephropathy in Patients With Renal Dysfunction Undergoing Coronary Angiography or Intervention
J. Am. Coll. Cardiol.,
August 19, 2008;
52(8):
599 - 604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Kuhn, N. Chen, D. V. Sahani, D. Reimer, E. J. R. van Beek, J. P. Heiken, and G. J. So
The PREDICT Study: A Randomized Double-Blind Comparison of Contrast-Induced Nephropathy After Low- or Isoosmolar Contrast Agent Exposure
Am. J. Roentgenol.,
July 1, 2008;
191(1):
151 - 157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. McCullough
Contrast-Induced Acute Kidney Injury
J. Am. Coll. Cardiol.,
April 15, 2008;
51(15):
1419 - 1428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Ritz
Cardiovascular Literature--Beyond Nephrology
Clin. J. Am. Soc. Nephrol.,
March 1, 2008;
3(2):
317 - 323.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Kelly, B. Dwamena, P. Cronin, S. J. Bernstein, and R. C. Carlos
Meta-analysis: Effectiveness of Drugs for Preventing Contrast-Induced Nephropathy
Ann Intern Med,
February 19, 2008;
148(4):
284 - 294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
American College of Cardiology/American Heart Asso, 2007 Writing Group to Review New Evidence and Upda, S. B. King III, S. C. Smith Jr, J. W. Hirshfeld Jr, A. K. Jacobs, D. A. Morrison, and D. O. Williams
2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention
J. Am. Coll. Cardiol.,
January 15, 2008;
51(2):
172 - 209.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. King III, S. C. Smith Jr, J. W. Hirshfeld Jr, A. K. Jacobs, D. A. Morrison, D. O. Williams, 2005 WRITING COMMITTEE MEMBERS, S. C. Smith Jr, T. E. Feldman, J. W. Hirshfeld Jr, et al.
2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee
Circulation,
January 15, 2008;
117(2):
261 - 295.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I-C. Tsai, T. Lee, W.-L. Tsai, M.-C. Chen, M.-J. Wu, W.-L. Lee, and H.-J. Ting
Contrast Enhancement in Cardiac MDCT: Comparison of Iodixanol 320 Versus Iohexol 350
Am. J. Roentgenol.,
January 1, 2008;
190(1):
W47 - W53.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al.
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
J. Am. Coll. Cardiol.,
August 14, 2007;
50(7):
e1 - e157.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. K. Laskey, C. Jenkins, F. Selzer, O. C. Marroquin, R. L. Wilensky, R. Glaser, H. A. Cohen, D. R. Holmes Jr, and for the NHLBI Dynamic Registry Investigators
Volume-to-Creatinine Clearance Ratio: A Pharmacokinetically Based Risk Factor for Prediction of Early Creatinine Increase After Percutaneous Coronary Intervention
J. Am. Coll. Cardiol.,
August 14, 2007;
50(7):
584 - 590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al.
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
J. Am. Coll. Cardiol.,
August 14, 2007;
50(7):
652 - 726.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Dixon, C. L. Grines, and W. W. O'Neill
The Year in Interventional Cardiology
J. Am. Coll. Cardiol.,
July 17, 2007;
50(3):
270 - 285.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Solomon, M. K. Natarajan, S. Doucet, S. K. Sharma, C. S. Staniloae, R. E. Katholi, J. L. Gelormini, M. Labinaz, A. E. Moreyra, and the Investigators of the CARE Study
Cardiac Angiography in Renally Impaired Patients (CARE) Study: A Randomized Double-Blind Trial of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease
Circulation,
June 26, 2007;
115(25):
3189 - 3196.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Jo, B.-K. Koo, T.-J. Youn, and H.-S. Kim
Reply.
J. Am. Coll. Cardiol.,
April 17, 2007;
49(15):
1669 - 1670.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Detrenis, M. Meschi, and G. Savazzi
Contrast Nephropathy: Isosmolar and Low-Osmolar Contrast Media
J. Am. Coll. Cardiol.,
February 27, 2007;
49(8):
922 - 922.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. McCullough, M. E. Bertrand, J. A. Brinker, and F. Stacul
Reply
J. Am. Coll. Cardiol.,
February 27, 2007;
49(8):
922 - 923.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, J. Narula, D. J. Sahn, et al.
Highlights of the Year in JACC 2006
J. Am. Coll. Cardiol.,
January 30, 2007;
49(4):
509 - 527.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Herzog
Kidney disease in cardiology
Nephrol. Dial. Transplant.,
January 1, 2007;
22(1):
43 - 46.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
