Highlights
– Women with incident stage 5 chronic kidney disease (CKD) in Alberta lost the population-level female survival advantage; excess mortality was greatest in younger women.
– Standardized mortality ratios (SMRs) vs the general population were markedly higher for women than men at younger ages (eg, age <55 years: SMR 40.9 vs 15.9).
– Within the cohort, 5-year all-cause mortality was higher for women younger than 55 (20.7% vs 14.6% for men).
– Women were less likely to receive kidney replacement therapy (KRT): younger women had lower transplant rates, and women ≥65 years were less likely to receive dialysis or transplant, independent of diabetes or cardiovascular disease.
Background
In the general population, female individuals have a survival advantage over male individuals across most age groups. Chronic kidney disease (CKD) is a major and growing global public health problem associated with high morbidity and mortality. Stage 5 CKD (end-stage kidney disease when kidney function is severely reduced but patients may not yet be receiving dialysis or transplant) marks a critical transition in prognosis and treatment decision-making. Whether the female survival advantage persists after development of stage 5 CKD and how sex influences access to kidney replacement therapy (KRT: dialysis or transplantation) are clinically important questions with implications for equity, resource planning, and outcomes.
Study design
Cohort and setting
This population-based cohort study (Chan et al., JAMA Internal Medicine, 2025) used linked administrative and kidney program data from Alberta, Canada, to identify adults (≥18 years) with incident non–KRT-dependent stage 5 CKD between April 2005 and March 2019. Patients were followed from study entry until death, out-migration, or March 2021.
Main outcomes and analytic approach
The investigators calculated sex-specific, age-stratified standardized mortality ratios (SMRs) using general population mortality data. Within the stage 5 CKD cohort, they used multistate models to estimate 5-year probabilities of all-cause death, initiation of maintenance dialysis, and receipt of kidney transplant, stratified by age and by presence of diabetes or cardiovascular disease.
Key findings
The study cohort included 7,506 adults with incident stage 5 CKD: 4,121 (54.9%) male and 3,385 (45.1%) female. Median age was 70 years (IQR 58–80) for men and 74 years (IQR 61–83) for women. Median follow-up was 7.9 years (IQR 4.7–11.5).
Excess mortality compared with the general population
Compared with age- and sex-matched general population mortality, women with stage 5 CKD experienced greater excess mortality than men, especially at younger ages. For adults younger than 55 years, the SMR was 40.9 (95% CI, 34.6–47.3) in women versus 15.9 (95% CI, 13.5–18.2) in men; the sex gap in excess mortality narrowed with advancing age.
Absolute mortality within the stage 5 CKD cohort
Within the CKD cohort, estimated 5-year all-cause mortality risks were higher for younger women than men (age <55 years: 20.7% in women vs 14.6% in men). At older ages, mortality risks were similar between sexes.
Receipt of kidney replacement therapy
Across age groups and comorbidity strata, female patients were less likely to transition to KRT. Women younger than 65 years were substantially less likely to receive a kidney transplant compared with men of the same age, regardless of diabetes or cardiovascular disease status. Women aged 65 years and older were less likely to receive either dialysis or transplant.
Patterns independent of measured comorbidity
These disparities in KRT receipt and the excess mortality observed in women persisted after stratifying by the presence of diabetes and cardiovascular disease, suggesting that measured comorbidity did not fully explain the sex differences.
Interpretation and clinical implications
This carefully conducted, population-based study in a universal health care setting demonstrates that the typical female survival advantage is absent — and in younger adults reversed — among people who reach stage 5 CKD. Importantly, women were less likely to receive life-prolonging KRT, with the largest gaps for transplantation among younger women and for dialysis/transplant among older women.
Possible explanations
Potential mechanisms fall into three broad and not mutually exclusive categories:
- Biological factors: Women and men differ in immunologic responses, body composition, and the prevalence of conditions that influence CKD progression and candidacy for KRT. For transplantation specifically, prior pregnancies can lead to HLA sensitization, which reduces the probability of receiving a compatible deceased-donor graft and prolongs time to transplantation.
- Health system and access factors: Differences in referral to nephrology, referral for transplant evaluation, listing practices, and organ allocation processes may disadvantage women. Even in universal health systems, structural barriers (transportation, caregiving responsibilities) and clinician bias can affect access to care.
- Patient-centered decision-making and preferences: Women may decline or delay initiation of dialysis at higher rates, or clinicians and patients may weigh quality-of-life or treatment burden differently. The dataset did not capture patient preferences, shared decision-making processes, or detailed functional/frailty measures that can influence treatment decisions.
Why younger women are particularly affected
The finding of the greatest excess mortality and lowest transplant rates among younger women is notable. Younger patients are typically more likely to be offered and to benefit from transplantation. Lower transplant rates in younger women may reflect higher sensitization from past pregnancies, differential referral, organ allocation factors, or unmeasured social determinants (eg, caregiving roles, employment, socioeconomic barriers) that disproportionately affect women of childbearing age.
Expert commentary and methodological considerations
The study’s strengths include a population-based design, linkage of administrative and specialty kidney program data, robust follow-up, and analytical methods that allowed estimation of both relative (SMR) and absolute (multistate model probabilities) outcomes. Conducting the study within a universal health care system (Alberta) reduces—but does not eliminate—financial access barriers, highlighting that inequities in outcomes may persist despite broad coverage.
Limitations include the observational design and potential for residual confounding. Important unmeasured variables include patient preferences, measures of frailty or functional status, social supports, detailed reasons for not initiating KRT, and immunologic sensitization status (eg, panel reactive antibody levels). Cause-specific mortality was not detailed in the summary data presented here. Additionally, findings from Alberta may not generalize to health systems with differing allocation policies, donor pools, or social contexts.
Implications for practice, policy, and research
Clinicians and programs should recognize that women with advanced CKD—particularly younger women—face disproportionate risks and lower rates of receiving potentially life-saving treatments. Practical actions include:
- Ensure timely referral to nephrology and early transplant evaluation, with protocols that minimize subjective gatekeeping and standardize criteria for evaluation and listing.
- Incorporate routine assessment of social determinants of health, caregiving responsibilities, and barriers to access into CKD care pathways and provide tailored supports (transportation, flexible scheduling, patient navigation).
- Improve data capture on patient preferences, frailty, immunologic sensitization, and reasons for non-initiation of KRT to inform personalized decision-making and programmatic interventions.
- Implement equity-focused quality improvement and audit measures that disaggregate KRT access and outcomes by sex, age, race/ethnicity, and socioeconomic status.
Research priorities include prospective studies that integrate biological markers (eg, HLA sensitization), granular psychosocial measures, and qualitative exploration of patient and clinician decision-making. Interventional trials or implementation studies testing referral and listing pathway changes, patient navigation, or prioritization approaches to reduce sex-based disparities would be valuable.
Conclusion
In this large, population-based cohort from a universal health care setting, women with incident stage 5 CKD did not experience the expected population-level survival advantage; younger women had the greatest excess mortality and were less likely to receive kidney transplants. The observed sex differences in KRT receipt persisted after accounting for diabetes and cardiovascular disease, indicating that comorbidity alone does not explain the disparities. These findings call for urgent attention to potential structural, social, and biological contributors, and for targeted measures to ensure equitable access to KRT and optimal outcomes for women with advanced CKD.
Funding and clinicaltrials.gov
Funding and trial registration details were not provided in the summary. See the original article for complete funding disclosures and conflicts of interest (Chan C et al., JAMA Internal Medicine 2025).
References
1. Chan C, Sawhney S, Ahmed SB, et al. Sex Differences in Mortality and Receipt of Kidney Replacement Therapy Among Adults With Stage 5 Chronic Kidney Disease. JAMA Intern Med. 2025 Nov 17. doi:10.1001/jamainternmed.2025.5979. Epub ahead of print. PMID: 41247715.
2. Carrero JJ, Hecking M, Chesnaye NC, Jager KJ. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol. 2018 Jun;14(3):151-164. doi:10.1038/nrneph.2017.181.
3. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):1–150. (KDIGO Work Group)
4. United States Renal Data System. 2020 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. (Use as reference for baseline KRT epidemiology and known disparities.)
Note: Additional references on pregnancy-related HLA sensitization and transplant access, and on sex differences in access to transplant and dialysis, can be found in the broader literature (see Carrero et al. 2018 review for an overview).
