Stage 5 CKD May Reverse Female Survival Advantage

New research on the sex differences in adults with stage 5 chronic kidney disease (CKD) suggests the female survival advantage observed in the general population may not apply to women with kidney disease, with females >55 years of age less likely to survive or receive a kidney transplant than their male counterparts.1

In the general population, women are more likely to outlive men by a 5.8-year gap, according to a previous study. In about 72% of 528 species of mammals, females live about 13% longer. Whether this mortality advantage persists in patients with chronic kidney disease has been previously unexamined.2

“To our knowledge, no population-based study has examined sex differences in mortality and treatment among individuals with incident stage 5 CKD. Prior studies have reported lower hazards of all-cause mortality and death without receiving KRT in female individuals with CKD compared with male individuals,” wrote study investigator, Christian Chan, PhD, postdoctoral associate at Cumming School of Medicine. “However, these studies were based on nephrology-referred cohorts with less advanced disease, limiting generalizability to individuals with stage 5 CKD and potentially introducing bias if referral patterns differ by sex.”1

To address this gap in research, investigators conducted a retrospective population-based cohort study leveraging data from administrative, laboratory, and provincial kidney programs in Alberta, Canada. The primary outcome assessed was all-cause death, found from Alberta Vital Statistics. Investigators established the study exposure as sex at cohort entry.1

To compare mortality rates, investigators stratified patients by 5-year age groups and calculated female-to-male mortality rate ratios for the patient cohort and the general population. Stage 5 CKD was defined as sustained eGFR <15 mL/min/1.73 m2 for > 3 months.1

The study included 7506 adults ≥ 18 years of age with incident stage 5 CKD. In the cohort, patients were categorized into groups of 18 to 44, 44 to 54, 55 to 64, 65 to 74, 75 to 84, and ≥ 84 years of age.1

In the cohort, 54.9% of participants were male (n = 4121), and 45.1% were female (n = 3385). Investigators included individuals whose legal sex might not reflect that assigned at birth (<0.1%). Female individuals met stage 5 CKD criteria at older ages than male individuals (median [IQR] age at first documentation of stage 5 CKD, 74 [61-83] years vs 70 [58-80] years), with similar baseline eGFR and qualifying period by sex.1

In a median 7.9-year follow-up, female individuals with stage 5 CKD experienced increased excess mortality than male patients, particularly at younger ages. Compared with the general population, standardized mortality ratios (SMRs) among those 20 to 44 years were 47.5 (95% Confidence Interval [CI], 34.7-60.3) for females and 12.0 (95% CI, 8.3-15.6) for males. At 65 to 74 years, SMRs were 14.1 (95% CI, 12.8-15.4) for females and 8.5 (95% CI, 7.9-9.2) for males, and by ≥85 years, SMRs were similar: 4.2 (95% CI, 3.9-4.5) for females and 4.1 (95% CI, 3.7-4.4) for males. Female-to-male mortality rate ratios showed a reversal of the usual female survival advantage in younger patients and a reduction in those with stage 5 CKD.1

At 5 years after a stage 5 CKD diagnosis, female patients had 58.9% (95% CI, 57.2-60.7) crude risks of all-cause mortality compared with 51.9% of males (95% CI, 50.3-53.5). Death without receiving KRT occurred in 39.9% of females (95% CI, 38.3-41.6) versus 28.3% of males (95% CI, 26.9-29.7). In female patients, 8.5% (95% CI, 7.5-9.5) received a transplant compared to 14.5% of males (95% CI, 13.4-15.7).1

Upon age-stratified analyses, investigators observed increased mortality in females <55 years, with similar risks between sexes in older age groups. In adjusted analyses, investigators increased all-cause mortality in females <45 years, increased death without kidney replacement therapy in those 65-74 years, and lower dialysis hazards in females ≥55 years.1

“These findings highlight the need for further research into the biological, structural, and societal factors influencing sex differences in treatment decisions and survival,1” concluded investigators.1

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 Internal Medicine. Published online November 17, 2025. doi:https://doi.org/10.1001/jamainternmed.2025.5979

2. Why do women live longer than men? A study offers clues to close the gap. NPR. Published October 6, 2025. https://www.npr.org/2025/10/06/nx-s1-5558184/women-men-longevity-health-life-span