Association of Serum Total Bilirubin Levels with Progressive Renal Decline and End-stage Kidney Disease: 10-year Observational Cohort Study in Japanese Patients with Diabetes

Objective: Previous reports have demonstrated the association of serum bilirubin levels with the progression of diabetic nephropathy. The objective of this study is to assess the association of basal bilirubin levels with progressive renal decline (PRD) and end-stage kidney disease (ESKD).

Methods: A total of 298 patients with diabetes who visited Kyushu University Hospital (Japan) were recruited and followed up for 10 years. PRD was defined as a negative change in estimated glomerular filtration ratio (eGFR) >3.7%/year, 2.5th percentile. Logistic regression analysis was performed to evaluate the association of total bilirubin levels with PRD and its cut-off point was determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier method and Cox hazard regression analysis were used to evaluate the predictive ability of its cut-off point for ESKD.

Results: Logistic regression model showed that total bilirubin levels were significantly associated with PRD, and ROC analysis showed that its cut-off point was 0.5 mg/dL. Kaplan-Meier method showed that the percent of patients who reached two endpoints, composite endpoint (ESKD or doubling of creatinine level) or 30% eGFR decline, was significantly higher in the low bilirubin group than in the high bilirubin group (18.5% vs 11.0%, P = 0.045; 49.1% vs 42.1%, P = 0.045, respectively, log-rank test). Cox hazard regression models confirmed the independence of the predictive ability of its cut-off point.

Conclusions: Serum total bilirubin levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL. It may be clinically useful for identifying patients at high risk of ESKD.