Kidney Week

Abstract: SA-PO118

Effects of Lanosterol Synthase Gene on the Development of AKI After Cardiac Surgery

Session Information

• AKI: Biomarkers, Imaging, Interventions
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Cocchini, Lorenzo, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Lorenzo Cocchini,

• D'Urbano, Luca, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Luca D'Urbano,

• Raimondo, Davide, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Davide Raimondo,

• De Filippo, Marta, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Marta De Filippo,

• Lanzani, Chiara, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Chiara Lanzani,

• Zagato, Laura, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Laura Zagato,

• Citterio, Lorena, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Lorena Citterio,

• Manunta, Paolo, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Paolo Manunta,

• Simonini, Marco, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Marco Simonini,

Background

Acute kidney injury (AKI) is a common post-surgery complication, significantly affecting morbidity and mortality. Recent studies reported that high plasma levels of endogenous ouabain (EO) are associated with 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. This work aims to analyze the relationship between this LSS polymorphism and the development of AKI after cardiac surgery.

Methods

1237 patients undergoing elective cardiac surgery were enrolled in the study. For each patient, preoperative biological samples and LSS genotypes were collected. Primary outcome was AKI development according to KDIGO guidelines.

Results

21.4% of patients developed AKI. Different preoperative clinical variables were analyzed, identifying five independent elements significantly correlated to AKI 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).
No significant differences were observed between preoperative EO plasma levels and allelic variants of the LSS gene; moreover, patients with the less common A allele were not associated with a more severe preoperative clinical presentation, expressed as EuroScore. LSS minor variants (A) turned out to be significantly associated with the incidence of AKI (AA=29.3%; AC=25.3%; CC=17.2%; X² p=0.001). This evidence remains significant after correction for covariates associated with 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 the 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.