Elevated bilirubin levels and risk of developing chronic kidney disease: a dose-response meta-analysis and systematic review of cohort studies

Int Urol Nephrol. 2018 Feb;50(2):275-287. doi: 10.1007/s11255-017-1675-y. Epub 2017 Aug 14.

Abstract

Aims: Previous studies have indicated the link of bilirubin levels and risk of developing chronic kidney disease (CKD); however, the findings were inconsistent.

Methods: We searched for cohort studies examining bilirubin as an exposure and CKD as an outcome in the Medline, EMBASE, and Web of Science databases from inception through November 31, 2016. A generalized least-squares approach was applied to assess the dose-response relationship between them by pooling rate ratios with 95% confidence intervals. Subgroup analyses, sensitivity analysis, meta-regression, and publication bias were also conducted.

Results: Seven cohort studies with 1316 cases and 21,076 participants were identified for inclusion in the meta-analysis. The combined RR for the highest versus lowest bilirubin level was 0.36 (95% CI 0.19-0.68; P heterogeneity = 0.001; Power = 0.72; n = 6). In the linear dose-response analysis, each 1-μmol/L increase in bilirubin was associated with a 5% reduced risk of CKD (RR = 0.95; 95% CI 0.92-0.97; P for trend test = 0.113; P heterogeneity = 0.001; Power = 0.99; n = 7). The subgroup analyses and sensitivity analyses showed consistent results, and publication bias may exist.

Conclusion: This meta-analysis suggests that elevated bilirubin level may be associated with decreased risk of developing CKD.

Keywords: Bilirubin; Chronic kidney disease; Cohort studies; Dose–response meta-analysis.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Bilirubin / blood*
  • Humans
  • Renal Insufficiency, Chronic / blood*
  • Risk Assessment
  • Statistics as Topic

Substances

  • Bilirubin