Relationship between serum total bilirubin levels and mortality in uremia patients undergoing long-term hemodialysis: A nationwide cohort study

Background and aims Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis. Methods This is a nationwide retrospective long-term cohort study. Patients were registered in the Taiwan Renal Registry Data System (TWRDS) from 2005 to 2012. A total of 115,535 hemodialysis patients were surveyed and those with valid baseline total bilirubin (TB) data were enrolled. All-cause mortality was the primary outcome. Results A total of 47,650 hemodialysis patients followed for 27.6 ± 12 months, were divided into 3 groups according to different baseline serum total bilirubin levels (0.1–0.3, 0.3–0.7, 0.7–1.2 mg/dL). Mean age was 61.4 ± 13.6 years, 50% were male, 13% were hepatitis B carriers, and 20% were hepatitis C carriers. Primary outcome was the 3-year mortality. The TB level 0.7–1.2 mg/dL group had high mortality, statistically significant hazard ratio of mortality was 1.14 (crude HR, 95% 1.07–1.20, p < 0.01), and adjusted HR was 1.18 (model 1, 95% CI 1.11–1.25), 1.21 (model 2, 95% CI 1.14–1.29, p < 0.01), 1.44 (model 3, 95% CI 1.06–1.96, p < 0.01), respectively. Sensitivity test showed that after excluding 14,899 patients with hepatitis B or C, or abnormal liver function, the highest level of TB associated with higher significant mortality was still robust. Conclusions In our study, high TB level is associated with mortality in uremia patients undergoing long-term hemodialysis, but further studies of the different effects of unconjugated or conjugated bilirubin on hemodialysis patients are needed.