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Sex-Associated Biomarker Differences in CKD Progression and Mortality
Thomas McDonnell1,2, Anthony Onoja3, Nicolas Vuilleumier4
1Donal O'Donoghue Renal Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom.
Clinical Journal of the American Society of Nephrology : CJASN
|February 5, 2026
Summary
Men with chronic kidney disease (CKD) face higher risks of kidney failure and death. Biomarker differences, particularly in inflammation and matrix deposition, explain these sex-based outcome disparities, suggesting a biological basis for worse male CKD prognosis.
Area of Science:
- Nephrology and Urology
- Biomarkers and Diagnostics
- Sex-Based Medicine
Background:
- Males with chronic kidney disease (CKD) exhibit poorer outcomes compared to females.
- This disparity is not fully explained by comorbidities or sociocultural factors.
- Investigating sex-based differences in biomarkers may elucidate the underlying risk mechanisms.
Purpose of the Study:
- To explore whether sex-based differences in specific biomarkers contribute to the observed disparity in CKD outcomes between males and females.
- To identify specific biomarkers associated with kidney injury, fibrosis, inflammation, and cardiovascular stress that differ between sexes in CKD patients.
Main Methods:
- Analysis of 1,680 males and 1,204 females with non-dialysis-dependent CKD from the NURTuRE-CKD cohort.
- Measurement of 21 biomarkers related to kidney injury, fibrosis, inflammation, and cardiovascular stress.
- Utilized multivariable Cox and Fine and Gray models for outcome assessment and ANCOVA for biomarker comparisons, adjusting for clinical factors.
Main Results:
- Significant sex differences in biomarker concentrations were observed in both controls and CKD participants.
- Males with CKD showed higher levels of inflammatory and extracellular matrix deposition biomarkers (e.g., KIM-1, GDF-15).
- Females with CKD had higher levels of matrix turnover and degradation markers (e.g., Osteoactivin, MMP-9).
- After adjusting for biomarker differences, the elevated risk of kidney failure and mortality associated with male sex was eliminated.
Conclusions:
- Male sex is independently associated with increased risk for kidney failure and mortality in CKD patients.
- Sex-specific biomarker profiles, reflecting distinct biological pathways, underlie these outcome differences.
- Adjustment for these biomarkers neutralizes the increased risk in males, highlighting a biological basis for sex disparities in CKD.
- Findings suggest potential for sex-specific therapeutic targets in CKD management.
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