Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery

Mark Stafford-Smith, Mihai Podgoreanu, Madhav Swaminathan, Barbara Phillips-Bute, Joseph P. Mathew, Elizabeth H. Hauser, Michelle P. Winn, Carmelo Milano, Dahlia M. Nielsen, Mike Smith, Richard Morris, Mark F. Newman, Debra A. Schwinn

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Background: Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. Methods: One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. Results: A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [ε4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). Conclusion: In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Original languageEnglish
Pages (from-to)519-530
Number of pages12
JournalAmerican Journal of Kidney Diseases
Volume45
Issue number3
DOIs
StatePublished - Mar 2005

Bibliographical note

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Acute renal failure (ARF)
  • Angiotensin-converting enzyme (ACE)
  • Associate study
  • Candidate genes
  • Cardiac surgery
  • Cardiopulmonary bypass (CPB)
  • Genetic
  • Heart surgery
  • Human
  • Intensive care
  • Polymorphism
  • Postoperative

ASJC Scopus subject areas

  • Nephrology

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