Commentary on “Association of Serum Total Bilirubin to Cholesterol Ratio With Progression of Chronic Kidney Disease in Patients With Type 2 Diabetes: A Retrospective Cohort Study”

Several key factors influencing bilirubin levels and lipid metabolism were not measured or adjusted for in the study. Notably, hemoglobin, which affects bilirubin metabolism [5], was not included in the analysis. Furthermore, longitudinal changes in body mass index (BMI), blood pressure, or albuminuria during follow-up were also not accounted for. These unmeasured confounders may influence the observed association between the TBIL/TC ratio and CKD progression.

Chen et al. have highlighted the potential of the TBIL/TC ratio as a biomarker for CKD progression in type 2 diabetes. However, the issues of outcome misclassification, medication confounding, and oversimplified threshold analyses necessitate cautious interpretation of their findings. Future studies should aim to: (1) Validate these findings in ambulatory cohorts using KDIGO-endorsed sustained eGFR decline criteria; (2) Integrate time-varying adjustments for nephroprotective medications and account for genetic and environmental confounders; (3) Report absolute risks and conduct decision-curve analyses to better evaluate the clinical utility of the TBIL/TC ratio. Addressing these limitations will help clarify whether the TBIL/TC ratio offers incremental value beyond established renal risk markers.

Tinghua Zhang: wrote, reviewed, and edited the manuscript. Additionally, he conceptualized the study concept and design.

The author declares no conflicts of interest.