Adam Lewis1, Lisa Bastarache1, Anita Pandit2, Daniel B Larach3, Jing He1, Anik Sinha4, Nicholas J Douville4,5, Michael Heung6, Michael R Mathis4,7, Jonathan D Mosley1,8, Jonathan P Wanderer3,1, Sachin Kheterpal4, Matthew Zawistowski2, Chad M Brummett4, Edward D Siew9, Cassianne Robinson-Cohen10, Miklos D Kertai11. 1. Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. 2. Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. 3. Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA. 5. Institute of Healthcare Policy & Innovation, University of Michigan, Ann Arbor, MI, USA. 6. Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 7. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. 8. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 9. Division of Nephrology and Hypertension, Vanderbilt Center for Kidney Disease (VCKD) and Integrated Program for AKI (VIP-AKI), Tennessee Valley Health System, Nashville Veterans Affairs Hospital, Nashville, TN, USA. 10. Vanderbilt O'Brien Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 11. Division of Adult Cardiothoracic Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, Medical Arts Building, Office 526E, Nashville, TN, 37212, USA. miklos.kertai@vumc.org.
Abstract
BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.
BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.
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