#6535 SEXUAL DIMORPHISMS OF ACUTE KIDNEY INJURY: DIVERGENT PERFORMANCES OF BIOMARKERS OR DIFFERENT MOLECULAR MECHANISMS?

Abstract Background and Aims Before implementing individualized strategies to prevent or treat acute kidney injury (AKI), identifying clusters of patients with common (or divergent) pathophysiological mechanisms, diagnosis criteria or outcome is of upmost importance. Method We compared the characteristics of 1170 male and female patients referred for cardiac surgery with cardiac bypass (CBP) using multivariate logistic regression and propension score-based analysis. Performances of the candidate urinary biomarkers neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7].[TIMP-2] product (Nephrocheck), and a recently developed AKI signature of 204 urinary peptides (PeptAKI) were compared, and sex-dependent individual urinary peptide changes were studied. Results In these patients referred for CBP-surgery, incidence and severity (K/DIGO classification) of AKI were similar in men and women (about 25%), even after adjustment of the usual risk factors of AKI including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. Performances of uNGAL, Nephrocheck and PeptAKI strongly diverged between males and females. In the overall cohort, as well as in sub-groups of males and females, the multi-markers PeptAKI signature outperformed uNGAL and NephroCheck. Reanalysis of peptides included in PeptAKI at the single peptide level suggested divergences of AKI mechanisms between sexes. In women, the peptide score-derived risk of AKI strongly relied on peptides indicating kidney inflammation (including SERPINs, SAA1, osteopontin, uromodulin fragments) and hemolysis (HBA1, HBB), whereas a peptide derived from a stress-responsive protective gene in kidney tubular epithelial cells (VGF nerve growth factor) was dramatically less abundant in women developing AKI. Conclusion In patients referred for CBP-surgery, significant clinical and biological differences between men and women, as well as sexual dimorphism of AKI biomarkers performances, were identified. Urinary peptide signatures may help to personalize prevention of AKI progression by giving both quantitative and sex-related qualitative information on molecular mechanisms underlying AKI.