The influence of biological sex on diagnostic markers of acute kidney injury in acute-on-chronic liver failure: insights from a single-centre tertiary care study.

Biological sex has a profound impact on disease severity, outcomes and diagnosis yet, its role in clinical disease is insufficiently explored. Acute on chronic liver failure (ACLF) is associated with high mortality and multiple organ dysfunctions, where acute kidney injury (AKI) significantly worsens prognosis. Here we investigated the impact of sex on the diagnostic parameters used for severity grading in ACLF. We enrolled 1,134 ACLF patients, and shortlisted 757 patients (636 males, 121 females) admitted to All India Institute of Medical Sciences, New Delhi, between 2016 and 2023. ACLF-AKI was defined and staged according to International Club of Ascites criteria. The impact of sex on baseline clinical parameters, AKI incidence, and progression were assessed using the statistical tools IBM SPSS 26.0 and GraphPad Prism 8.0. Males exhibited a higher incidence of AKI (48.34%) compared to females (28.09%). However, no significant sex-based differences were observed in AKI stages. Males also had an overall high absolute value of sCr and blood urea compared to females. However, female ACLF patients who developed AKI exhibited a significantly higher ΔsCr levels compared to males ( = 0.003). Kaplan-Meier analysis revealed that males developed AKI significantly faster (median 2 days) than females (median 5 days) during the first week of hospitalization. In conclusion, sex-based differences were observed in the widely used diagnostic criteria of sCr and ΔsCr for AKI in patients with ACLF. Although these findings are preliminary our results reveal sex-specific differences in sCr-based AKI diagnosis and risk stratification in ACLF which warrant further validation in prospective multi-centric cohort studies.