Clinical Investigation

Kidney International (1995) 47, 254–261; doi:10.1038/ki.1995.32

Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: A randomized trial

Michael R Rudnick, Stanley Goldfarb, Lewis Wexler, Philip A Ludbrook, Mary J Murphy, Elkan F Halpern, James A Hill, Michael Winniford, Martin B Cohen, Douglas B VanFossen and for the Iohexol Cooperative Study1

Division of Nephrology, The Graduate Hospital, University of Pennsylvania School of Medicine, and Division of Nephrology, Hospital of the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Department of Radiology, Stanford University Hospital, Stanford University School of Medicine, Stanford, California; Division of Cardiology, Barnes Hospital, Washington University School of Medicine, St. Louis, Missouri; Sanofi Winthrop Pharmaceuticals, New York, New York; Center for Imaging and Pharmaceutical Research, The Massachusetts General Hospital, Boston, Massachusetts; Division of Cardiology, Shands Hospital, University of Florida College of Medicine, Gainsville, Florida; Division of Cardiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Division of Cardiology, Westchester County Medical Center, New York Medical College, Valhalla, New York; and Division of Cardiology, The Ohio State University Hospital, Ohio State University College of Medicine, Columbus, Ohio, USA

Correspondence: Michael R Rudnick MD, Section of Nephrology, The Graduate Hospital, Pepper Pavilion - 703, 19th & Lombard Streets, Philadelphia, Pennsylvania 19146, USA.

1The Iohexol Cooperative Study includes the following investigators and institutions:Participating Centers: The Graduate Hospital (Philadelphia, PA); *Michael R. Rudnick, Thomas H. Kreulen, Hratch Kasparian, Ronald S. Gottlieb, Raphael Cohen, Jeffrey S. Berns, Peter R. Duca, Ave Maria Irwin Maloney; Boston University Medical Center (Boston, MA); *Michael A. Bettmann, David Parker Faxon, Alice K. Jacobs, Alan J. Greenfield, Thomas Gregory Walker, Beldon A. Idelson, Mary Ann Barry; St. Luke's Hospital (Kansas City, MO); *Gary Beauchamp, Janardarna Sharma, Susan Anderson, Georgia Dittmeier; Stanford University Hospital (Stanford, CA); *Lewis Wexler, Tim Alexander Fischell, Walter Wai-Tak Chien, Robert S. Swenson, Catherine A. Kusnick, Evaleen Kay Jones, Linda Raish Yen, William Lim Fong, Helen J. Gordon, Cesar R. Molina, John C. Giacomini, Keith Terasaki, John Edwin Atwood, David Corbly Swanson, Daniel E. Lucus, Ann Cline, Pam Gallant; Hospital of the University of Pennsylvania (Philadelphia, PA); *Stanley Goldfarb, John Hirshfeld, Jr., William G. Kussmaul III, Howard Craig Herrmann, Warren K. Laskey, Sarah Spinier; Ochsner Foundation Hospital (New Orleans, LA); *Christopher White, J. Timothy Walsh, Vernon A. Valentino, Louis Mailander, Minh Q. Nguyen, Joseph A. Pedone, Roland J. Bourgeois, Jr. Michael Oapos;Dowd, Hector O. Ventura, Herman Price, Stephen R. Ramee, Deborah Hunt Simonson, Kathy Arcement Hébert, Tyrone Jean Collins, Andrew Peter Ross, James E. Rose, James R. Stinebaugh, Jr., George Louis Bakris, Kim Covington; Swedish Hospital Medical Center (Seattle, WA); *R. Jeffrey Westcott, John L. Peterson, John Philips; Washington University School of Medicine (St. Louis, MO); *Philip Albert Ludbrook, Alan J. Tiefenbrunn, Robert G. Kopitsky, Nancy Ricciotti; Latter Day Saints Hospital (Salt Lake City, UT); *Hiram W. Marshall, Robert E. Bond, Jeffrey Lance Anderson, Ann Allen; The Christ Hospital (Cincinnati OH); *Dean J. Kereiakes, Thomas M. Broderick, Charles W. Abbottsmith, Robert J. Toltzis, Linda Martin; St. Elizabeth's Hospital (Boston, MA); *Jeffrey Michael Isner, Douglas William Losordo, Susan Kelly, Ann Pieczak; The Methodist Hospital (Houston, TX); *Clement A. DeFelice, Albert E. Raizner, William R. Gaston, William Richard Cash-ion, Jr., Mark John Hausknecht, Neal Stephen Kleiman, John M. Lewis, James Dwayne Pickett, Roberto Bolli, Jacques Heibig, Scott Loren Harris, Michael Davis, Monique Roberts; Portland VA Medical Center (Portland, OR); *Henry DeMots, George David Giraud, Edward S. Murphy, Robert T. Palac, Richard Gene Gay, Mark Gilbert; Westchester County Medical Center (Valhalla, NY); *Martin B. Cohen, Meivin B. Weiss, AnnMarie Kanakaraj; *Medical College of Virginia; *George Vetrovec, Michael Cowley, Germano DiSciascio, Evelyne Goudreau, Ravinder Kohli, Nagui Sabri, Mark F. Warner, Mary Brodie; The Ohio State University Hospital (Columbus, OH); *Douglas B. Van Fossen, James Phillip Bacon, Charles Arthur Bush, Mary Elizabeth Fontana, Albert Joseph Kolibash, Jr., Raymond Daniel Magorien, Jr., Mary Jo Rumancik; Minneapolis Heart Institute Foundation (Minneapolis, MN); *Irvin F. Goldenberg, Wesley R. Pedersen, Susanne K. Roeller, Lynn Berchtold; University of Florida (Gainesville, FL)- *James Hill, Charles R. Lambert, Elizabeth Franco; University of Maryland Hospital (Baltimore, MD); *Carl Tommaso, Matthew R. Weir, J. Lawrence Stafford, Rodney A. Johnson, Acquanetta Lancaster, Pat Colegrove; Bishop Clarkson Memorial Hospital (Omaha, NE); *Vincent Frank Miscia, Ward A. Chambers, Richard R. Miles, David G. Meyers, Thomas D. Sears, Douglas V. Welsh, Linda Durbin; University of Iowa Hospital (Iowa City, Iowa); *Michael D. Winniford, James D. Rossen, David W. Ferguson, Charlotte L. Talman, Gail Reynolds; VA Lakeside Hospital (Chicago, IL); *Pierre Abi-Mansour, Lloyd William Klein, Lydia Andruszyn; Sinai Samaritan Medical Center (Milwaukee, WI); *Donald H. Schmidt, Tanvir Khalid Bajwa, Cheryl Ann Maglio, Cheryl Richardson.Advisory and Safety Monitoring Committee: Joseph L. Fleiss, Edward W. Gertz, David Goldsmith, H. David Humes, and Roger W. Sherwin.*Principal Investigator

Received 6 June 1994; Revised 29 July 1994; Accepted 1 August 1994.

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Abstract

Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: A randomized trial. The incidence of nephrotoxicity occurring with the nonionic contrast agent, iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared in 1196 patients undergoing cardiac angiography in a prospective, randomized, double-blind multicenter trial. Patients were stratified into four groups: renal insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N = 216). Serum creatinine levels were measured at – 18 to 24, 0, and 24, 48, and 72 hours following contrast administration. Prophylactic hydration was administered pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of greater than or equal to1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002. Differences in nephrotoxicity between the two contrast groups were confined to patients with RI alone or combined with DM. In a multivariate analysis, baseline serum creatinine, male gender, DM, volume of contrast agent, and RI were independently related to the risk of nephrotoxicity. Patients with RI receiving diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to those receiving iohexol. Clinically severe adverse renal events were uncommon (N = 15) and did not differ in incidence between contrast groups (iohexol N = 6; diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography, only those with pre-existing RI alone or combined with DM are at higher risk for acute contrast nephrotoxicity. The incidence of acute nephrotoxicity in these high-risk patients is significantly less with the nonionic contrast media iohexol compared to the ionic contrast agent diatrizoate.

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