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Background <p>Current evidence remains limited regarding associations between serum indirect bilirubin (IBIL) levels and chronic kidney disease (CKD) risk, particularly in gender-stratified analyses. This study investigated the gender-specific relationship between serum IBIL and CKD incidence.</p> Methods <p>Using data from a prospective cohort in northwestern China, we followed 25,684 CKD-free participants. Cox proportional hazards models and restricted cubic spline regression were employed to assess IBIL-CKD associations. The discriminatory performance of IBIL was evaluated through ROC curve analysis. Robustness of results was examined via subgroup and sensitivity analyses.</p> Results <p>Over 122,401.17 person-years of follow-up, 1,219 incident CKD cases were identified. Adjusted hazard ratios (95% CIs) for CKD were 0.799 (0.679–0.940) overall and 0.718 (0.693–0.869) among males. Area under the curve (AUC) values were 0.710 (0.704–0.715; <i>p</i> &lt; 0.001) overall, 0.710 (0.703–0.718; <i>p</i> &lt; 0.001) for males, and 0.679 (0.670–0.688; <i>p</i> &lt; 0.001) for females. A formal test for interaction confirmed that the association was significantly modified by sex (p for interaction &lt; 0.001). A linear dose-response pattern was observed exclusively in males. Results remained consistent across subgroup and sensitivity analyses.</p> Conclusions <p>Our findings reveals a significant sex interaction in the association between serum IBIL and CKD. The inverse association is robust, exhibits a linear dose-response relationship, and is statistically significant exclusively in males. These findings position serum IBIL as a sexually dimorphic factor linked to CKD risk, underscoring the necessity of considering gender in both the research and potential risk assessment of oxidative stress-related pathways in renal disease.</p>

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Gender-specific associations between serum indirect bilirubin and chronic kidney disease risk: a prospective cohort study highlighting a protective effect confined to males

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月2日

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  • Jinlong You,
  • Xue Wang,
  • Jing Tang,
  • Xiuqian Li,
  • Rui Wang,
  • Yuanyuan Li,
  • Chun Yin,
  • Yana Bai,
  • Minzhen Wang,
  • Shan Zheng

摘要

Background

Current evidence remains limited regarding associations between serum indirect bilirubin (IBIL) levels and chronic kidney disease (CKD) risk, particularly in gender-stratified analyses. This study investigated the gender-specific relationship between serum IBIL and CKD incidence.

Methods

Using data from a prospective cohort in northwestern China, we followed 25,684 CKD-free participants. Cox proportional hazards models and restricted cubic spline regression were employed to assess IBIL-CKD associations. The discriminatory performance of IBIL was evaluated through ROC curve analysis. Robustness of results was examined via subgroup and sensitivity analyses.

Results

Over 122,401.17 person-years of follow-up, 1,219 incident CKD cases were identified. Adjusted hazard ratios (95% CIs) for CKD were 0.799 (0.679–0.940) overall and 0.718 (0.693–0.869) among males. Area under the curve (AUC) values were 0.710 (0.704–0.715; p < 0.001) overall, 0.710 (0.703–0.718; p < 0.001) for males, and 0.679 (0.670–0.688; p < 0.001) for females. A formal test for interaction confirmed that the association was significantly modified by sex (p for interaction < 0.001). A linear dose-response pattern was observed exclusively in males. Results remained consistent across subgroup and sensitivity analyses.

Conclusions

Our findings reveals a significant sex interaction in the association between serum IBIL and CKD. The inverse association is robust, exhibits a linear dose-response relationship, and is statistically significant exclusively in males. These findings position serum IBIL as a sexually dimorphic factor linked to CKD risk, underscoring the necessity of considering gender in both the research and potential risk assessment of oxidative stress-related pathways in renal disease.