Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci

Abstract

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery dataset consisted of 873 non-emergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication dataset had 380 cardiac surgical patients (CATHGEN). Single nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine-mapping using imputed SNPs across these two regions and meta-analysis found genome wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review

“…Low cardiac output and insult may also warrant the use of preoperative intra-aortic balloon pump, which has also been associated with development of postoperative AKI, as suggested by Rosner et al [8] Recently, genetic predisposition to AKI has been studied. Stafford Smith et al conducted an unbiased genome-wide associated study which identified two new loci, namely rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3), that increased the risk of AKI following coronary artery bypass grafting (CABG) [10] . The authors also speculated that their findings may become a predictive tool to improve individualised AKI risk stratification in cardiac surgery patients.…”

No association between donor age and recipient outcomes: transfusion of plasma in patients undergoing coronary artery bypass grafting surgery

“…Postoperative AKI was defined as a 50% or greater increase or a rise greater than 0.3 mg/dL in serum creatinine within any 48-hour window. 12 …”

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

“…The cohort identified for the current substudy has a limited overlap with participants in prior published analyses involving other postoperative outcomes, some of which reflect more recently enrolled patients. 24-26 …”