Associations of low serum total bilirubin level with all-cause mortality and cardiovascular mortality in peritoneal dialysis patients

Objective To investigate the association of low serum total bilirubin (TBIL) level with all-cause mortality and cardiovascular mortality in peritoneal dialysis patients. Methods As a single-center, retrospective, cohort study, all the patients who underwent peritoneal dialysis catheterization in the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University and started peritoneal dialysis for more than 3 months from January 1, 2006 to December 31, 2010 were included. Demographics, baseline clinical and laboratory test results were collected. All patients were followed up until December 31, 2012. Patients were divided into 4 groups according to their baseline serum TBIL levels (interquartile range). Kaplan-Meier method was used to compare the survival rate of each group. Cox regression model was used to analyze the association of TBIL with all-cause mortality and cardiovascular mortality. Logistic regression was used to analyze the influencing factors of low TBIL level. Results A total of 880 peritoneal dialysis patients with baseline TBIL data were enrolled in this study, with age of (48.0±15.4) years old, among whom 59.0% were male. Median TBIL was 4.5 μmol/L and interquartile range was 3.4-5.8 μmol/L. The comparison between TBIL quartile groups showed that the difference in proportion of diabetics, Charlson comorbidity index, hemoglobin, serum albumin, serum calcium, intact parathyroid hormone, urea nitrogen, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was statistically significant (all P<0.05), while the difference in body mass index (BMI), estimated glomerular filtration rate, serum creatinine, urea nitrogen, uric acid and phosphorus was not statistically significant. After a median follow-up of 31 months, 194 patients died, 104 of which were cardiovascular deaths. Kaplan-Meier curves showed higher all-cause mortality in patients with TBIL≤3.4 μmol/L (Q1 group) (P=0.032) and there was no statistical difference in the cardiovascular mortality among different groups. After adjusting for biochemical indicators such as demographics, comorbidities, and liver function, taking baseline TBIL Q2 level (3.4<TBIL≤4.5 μmol/L) as a reference, the hazard ratio for all-cause death in patients with TBIL≤3.4 μmol/L was 1.702 (95%CI 1.093-2.650, P=0.019), and the hazard ratio for cardiovascular death was 1.760 (95%CI 0.960-3.227, P=0.068). Multiple logistic regression analysis results showed that diabetes (OR=1.065, 95%CI 1.010-1.122, P=0.019) and high BMI (OR=1.838, 95%CI 1.056-3.197, P=0.031) were risk factors for baseline serum TBIL≤3.4 μmol/L. However, high hemoglobin (OR=0.990, 95%CI 0.982-0.998, P=0.011), high serum albumin (OR=0.950, 95%CI 0.916-0.985, P=0.006) and high ALT (OR=0.998, 95%CI 0.976-0.999, P=0.036) were the protective factors for patients with baseline serum TBIL≤3.4 μmol/L. Conclusion Baseline serum TBIL≤3.4 μmol/L in peritoneal dialysis patients is independently associated with all-cause mortality, and is not significantly associated with cardiovascular mortality; and baseline serum TBIL≤3.4 μmol/L occurred is associated with diabetes, high body mass index, low levels of hemoglobin, serum albumin and ALT. Key words: Peritoneal dialysis; Bilirubin; Mortality; Cardiovascular mortality