Association between total bilirubin levels and the risk of acute kidney injury: a large hospital- based cohort study

Acute kidney injury (AKI) is a common hospital-acquired condition linked to oxidative stress and poor outcomes. Bilirubin exerts dual, level-dependent effects, acting as an antioxidant within mildly elevated levels yet becoming cytotoxic when markedly elevated. While moderate bilirubin elevation shows long-term kidney benefits, its association with AKI remains unclear. This retrospective cohort study included adult patients admitted between 2018 - 2020 with total bilirubin (TBIL) below 1.5 times the upper limit of normal (<30 μmol/L). The primary outcome was in-hospital AKI, defined by the Kidney Disease: Improving Global Outcomes criteria. Patients were stratified into high and low TBIL groups based on the median. Restricted cubic splines examined potential nonlinear relationships between TBIL and AKI. Cox regression assessed the association of TBIL as a continuous variable with in-hospital AKI and mortality. Subgroup analyses included age, sex, diabetes mellitus, white blood cell count, abnormal liver function, direct/indirect bilirubin ratio, and serum albumin. Among 29,261 hospitalized patients, in-hospital AKI occurred in 785 patients (2.68%). Unadjusted analysis revealed a U-shaped relationship between TBIL and AKI risk (P-overall = 0.004, P-nonlinear = 0.002), whereas the nonlinear component was attenuated after multivariable adjustment (P-overall = 0.001, P-nonlinear = 0.09). Multivariable Cox regression showed higher TBIL levels were independently associated with increased risks of in-hospital AKI (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.06–1.22) and mortality (HR 1.26, 95% CI 1.02–1.54). Results were consistent across all subgroups. Higher TBIL levels, even within the normal to mildly elevated range, were independently associated with increased risks of in-hospital AKI and mortality.