#1954 Effects of lanosterol synthase (LSS) gene on the development of acute kidney injury after cardiac surgery

Abstract Background and Aims Acute kidney injury (AKI) is a common post-cardiac surgery complication, significantly affecting morbidity and mortality. Recent studies reported that high plasma levels of endogenous ouabain (EO), a stress hormone secreted by the adrenal glands, are associated to worse kidney outcomes after cardiac surgery. Our group demonstrated that EO activity is affected by a missense variant (rs2254524, C -> A, Val642Leu) in Lanosterol Synthase (LSS) gene, an enzyme implicated in EO synthesis. The aim of this work is to analyze the relationship between this LSS polymorphism and the development of AKI after cardiac surgery. Method 1237 patients undergoing elective cardiac surgery were enrolled in the study. Preoperative biological samples were collected (Table 1). LSS genotypes were determined for each patient. The primary outcome was AKI development, according to KDIGO 2012 guidelines. Results 21.4% of patients developed AKI. Different preoperative clinical variables were analyzed, identifying five independent risk factors significantly correlated to AKI development in multivariate logistic regression analysis: age (p < 0.001), FE (p = 0.005), NYHA class (p < 0.001), reoperation (p = 0.002) and complex surgical intervention (p < 0.001), Table 2. No significant differences were observed between preoperative EO plasma levels and allelic variants of LSS gene and patients with the less common A allele were not associated to a more severe preoperative clinical presentation, expressed as EuroScore II value (AA 2.54 ± 3.86 vs AC 2.15 ± 2.52 vs CC 2.04 ± 2.73; p = ns). LSS minor variants turned out significantly associated with the incidence of AKI (AA = 29.3%; AC = 25.3%; CC = 17.2%; X2 p < 0.001—Fig. 1). This evidence remains significant after correction for covariates associated to AKI previously reported (Log regression p = 0.002; RR for AA variant: 2.09 (IC95% 1.15-3.78)) Conclusion Patients with at least one mutated allele of LSS variant have a higher probability of developing AKI after cardiac surgery. We think these results could be of interest to further understand cellular mechanisms underlying AKI development, especially in the cardiac surgery field.