The Inflammation Effect in the Association Between Bilirubin and Chronic Kidney Disease in Patients with Type 2 Diabetes: A Retrospective Cohort Study

Background: The associations of bilirubin (BIL) and systemic inflammation with chronic kidney disease (CKD) remain unclear. This study examined associations among BIL, systemic inflammation, and CKD progression in type 2 diabetes patients, assessing systemic inflammation's mediating role. Methods: This retrospective cohort study included 1215 subjects. The exposure was baseline BIL concentrations, while inflammation-related indicators including systemic inflammatory response index (SIRI) and systemic immune-inflammation index (SII). The main outcome was the first event of CKD progression, characterized by a decrease in the estimated glomerular filtration rate (eGFR) stage, with a sustained ≥25% decline in eGFR from baseline, confirmed by two consecutive measurements ≥3 months apart. Cox proportional hazards models assessed associations between BIL, systemic inflammation, and CKD progression. Subgroup and sensitivity analyses were also conducted. Restricted cubic splines (RCS), and mediation analysis were performed to assess the nonlinear associations and mediating role of systemic inflammation. Results: for nonlinear < 0.001) with CKD progression. Cox regression models showed the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for TBIL and IBIL were 0.92 (95% CI: 0.89, 0.96) and 0.90 (95% CI: 0.85, 0.94), respectively. Subgroup and sensitivity analyses reinforced the findings, demonstrating consistent outcomes across demographic groups and under varied analytical conditions. The modest mediating effects were observed for SIRI (5.21%) and SII (5.50%) with TBIL, and for SIRI (7.17%) and SII (6.92%) with IBIL. However, these correlations were not observed with direct bilirubin (DBIL). Conclusion: Lower BIL levels (especially IBIL) were inversely associated with CKD progression risk in type 2 diabetes, with systemic inflammation partially mediating this relationship.