Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients

Background: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated wit 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 hypothesis that apolipoprotein E allele are associated wit different postoperative changes in serum creatinine after cardiac surgery. Methods: The authors performed a prospective observational study wit use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein 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 epsilon 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 postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon 2 and epsilon 3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs epsilon 3, P = 0.038 vs. epsilon 2). There was no difference in baseline creatinine among allele groups. Conclusions: Inheritance of the apolipoprotein epsilon 4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon 3 or epsilon 2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.