Kidney Transplantation Attenuates Excess Cardiovascular Risk in Women with Kidney Failure

Background: Cardiovascular (CV) disease is the leading cause of death among individuals with chronic kidney disease (CKD) including kidney replacement therapy (KRT). However, real-world evidence on sex differences in excess CV risk, risk relative to the population with normal kidney function, remains limited in this population. Methods: This retrospective cohort study utilized de-identified electronic medical records data from TriNetX US Collaborative Network encompassing 69 health care organizations. Adult participants aged ≥ 18 years were included and categorized into eight groups based on kidney function: women or men with functioning first kidney transplant, women or men on maintenance dialysis, women or men with CKD but without prior (KRT), and women or men without CKD. The primary outcome was major adverse cardiac events (MACE). Multivariable Cox proportional hazards models were used to adjust for a range of risk factors, including age, sociodemographic characteristics, and covariates related to hypertension, diabetes, metabolic syndrome, prior CV disease, and inflammation. Results: A total of 18948 women and 24373 men were included in the kidney transplant group, 19062 women and 27255 men in the dialysis group, 17997 women and 19385 men in the CKD group, and 120184 women and 107694 men in the group without CKD. Women exhibited greater excess CV risk across all stages of kidney function compared to men. Kidney transplantation attenuated the sex difference in excess cardiovascular risk compared to dialysis, with women showing an aHR of 2.63 (95% CI: 2.46-2.82) and men an aHR of 2.02 (95% CI: 1.90-2.15), versus women on dialysis with an aHR of 8.42 (95% CI: 7.89-8.99) and men with an aHR of 5.77 (95% CI: 5.42-6.14). However, the sex difference in excess CV risk remained greater after kidney transplantation compared to the CKD population without prior KRT (women aHR 1.84, 95%CI: 1.73-1.96; men aHR 1.61, 95%CI: 1.53-1.70), with women at disadvantage. Conclusion: Women with impaired kidney function consistently showed greater excess CV risk than men. Kidney transplantation reduced this sex difference among those with kidney failure.