Anesthesiology 2000; 93:325–31 © 2000 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Preliminary Report on the Association of Apolipoprotein E Polymorphisms, with Postoperative Peak Serum Creatinine Concentrations in Cardiac Surgical Patients Sophia T. H. Chew, F.A.N.Z.C.A.,* Mark F. Newman, M.D.,† William D. White, M.P.H.,‡ Peter J. Conlon, F.R.C.P.I.,§ Ann M. Saunders, Ph.D., Warren J. Strittmatter, M.D.,# Kevin Landolfo, M.D.,** Hilary P. Grocott, F.R.C.P.C.,†† Mark Stafford-Smith, F.R.C.P.C.†† Background: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hy- pothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. Methods: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical pa- tients who were enrolled in an ongoing investigation of apoli- poprotein E genotypes and organ dysfunction at a university hospital between 1989 –1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. Results: The 4 allele grouping (E2  2/2,2/3,2/4; E3  3/3; E4  3/4,4/4) was associated with a smaller increase in postop- erative serum creatinine (perioperative change: E4, 0.17; E3, 0.26; E4, 0.27 mg/dl) and a lower peak postoperative creat- inine than the 2 and 3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P  0.015 vs. 3, P  0.038 vs. 2). There was no difference in baseline creatinine among allele groups. Conclusions: Inheritance of the apolipoprotein 4 allele is associated with reduced postoperative increase in serum creat- inine after cardiac surgery, compared with the 3 or 2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratifica- tion for cardiac surgery and raise questions regarding apoli- poprotein E and the pathophysiology of acute renal injury. (Key words: Acute renal failure; heart surgery; postoperative compli- cations.) OF the 800,000 patients who undergo coronary artery bypass surgery worldwide annually, 1 approximately 8% will experience a significant perioperative acute renal injury, and up to 1% will require dialysis. 2–4 Acute renal injury after cardiac surgery is important because even minor degrees of postoperative renal dysfunction are associated with major in-hospital increases in morbidity, mortality, and cost. 2,3,5 Acute renal failure is indepen- dently associated with mortality after cardiac surgery, 6 with rates increasing from less than 1% in unaffected patients to 20% in patients with moderate acute renal injury, exceeding 60% for patients requiring dialysis. 2–4 * Cardiothoracic Fellow, Department of Anesthesiology, Duke Uni- versity Medical Center. † Professor, Department of Anesthesiology, Duke University Medical Center. ‡ Senior Statician, Department of Anesthesiology, Duke University Medical Center. § Consultant, Department of Medicine, Division of Nephrology, Duke University Medical Center; Department of Medicine, Beaumont Hospital, Dublin, Ireland.  Assistant Professor, Department of Medicine, Division of Neurol- ogy, Duke University Medical Center. # Professor, Department of Medicine, Division of Neurology, Duke University Medical Center. ** Assistant Professor, Department of Surgery, Duke University Med- ical Center. †† Associate Professor, Department of Anesthesiology, Duke Univer- sity Medical Center. Received from the Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina. Submitted for publication August 31, 1999. Accepted for publication January 28, 2000. Sup- ported in part by the Division of Cardiothoracic Anesthesia, Duke University Medical Center, Durham, North Carolina; by the American Heart Association grant-in-aid 9510970; and by the National Institutes of Health grant R01 HL54316-01 (to Dr. Newman), Bethesda, Maryland. Results presented in abstract form at the Association of University Anesthesiologists’ 46th Annual Meeting, Pittsburgh, Pennsylvania, May 16, 1999. Address reprint requests to Dr. Stafford-Smith: Department of Anes- thesiology, Box 3094, Duke University Medical Center, Durham, North Carolina 27710. Address electronic mail to: staff002@mc.duke.edu Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org 325 Anesthesiology, V 93, No 2, Aug 2000