Serum Total Bilirubin and Progression of Chronic Kidney Disease and Mortality: A Systematic Review and Meta-Analysis

Abstract

Background: Previous studies have suggested that serum total bilirubin (STB) levels are associated with heightened chronic kidney disease (CKD) and mortality in both the general population and nephropathy patients. However, these results remain inconsistent. The aim of our study was to investigate whether STB was a predictor for progression of CKD and mortality by meta-analysis.Methods: We performed a systematic literature search in PubMed, Web of Science, MEDLINE, EMBASE, Google Scholar, and Cochrane Library's database up to June 30, 2019. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were extracted for the highest vs. lowest category STB levels within the physiological range, and a random-effects model was applied to calculate the dose–response relationships. A pooled hazard ratio (HR) was used to investigate the association between STB levels and mortality in dialysis patients.Results: A total of 16 studies, wherein participants were followed from 21 months to 7 years, were eligible for inclusion in the study. For the categorized STB, 11 studies with 41,188 participants were identified and analyzed. Patients with the highest STB levels were associated with a lower risk of CKD (RR = 0.64; 95% CI 0.55–0.73) compared to those with the lowest STB levels. Furthermore, based on seven studies, a pooled RR of 0.89, 95% CI (0.80–0.99) was observed for the continuous STB levels (per 0.2 mg/dL increase). Four studies that included 51,764 participants illustrated that there was no association between STB levels and all-cause mortality (HR = 0.77; 95% CI 0.42–1.41). A prominent negative linear relationship (X2 = 14.70; P = 0.0001) was found between STB levels and risk of CKD. Subgroup analyses showed that there were no significant differences in the subgroup adjustment factor except for sample size.Conclusions: Elevated STB levels within a physiological range are associated with lower risk of CKD regardless of the study characteristics and coincide with a liner dose–response relationship. However, whether high STB levels are a protective factor against mortality remains inconclusive. Large-scale randomized controlled trails are needed to target STB levels for predicting renal outcomes.

A Retrospective Study from a Single Center in China to Develop a Nomogram to Predict One-Year Mortality in Patients with End-Stage Renal Disease Who Are Receiving Hemodialysis

“…Similarly, Su, et al, also proposed that a high TBIL level was associated with mortality among uremia patients undergoing long-term HD [ 21 ]. However, some studies have also shown that bilirubin has antioxidant properties and might be negatively correlated with the mortality for HD patients [ 25 , 26 ], which was inconsistent with our results. The possible reason was considered as the population selection.…”

Bilirubin levels and kidney function decline: An analysis of clinical trial and real world data

“…Similarly, other observational studies have shown associations between naturally elevated circulating bilirubin levels and a slower CKD progression in patients with and without diabetes [ 1 , 6 – 28 ]. This association has however been mainly demonstrated in Asian populations; hence, it is uncertain if the results can be expanded to non-Asian populations.…”

High‐normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real‐world study

“…For example, a metaanalysis consisting of 16 studies showed that elevated serum total bilirubin (STB) levels within a physiological range reduced the risk and mortality of CKD. 26 Similarly, several clinical studies in T2DM subjects also observed a reverse correlation between STB and CKD, [27][28][29][30] and follow-up changes in STB were also found to be significantly associated with the progression of CKD in male patients with diabetes. 29 Although many studies investigated the association between serum bilirubin (SB) levels and CKD and the effect of bilirubin on CKD in general and diabetic populations, most discussions mainly focused on STB and did not distinguish conjugated bilirubin (CB) and unconjugated bilirubin (UCB) in their studies.…”