Sex Dimorphism in Vascular Trajectories After Living-Donor Kidney Transplantation: A Prospective Exploratory Cohort Study
Camillo Tancredi Strizzi, Samsul Arefin, Leah Hernandez, Awahan Raheman, Francesco Pesce, Giuseppe Grandaliano, Peter Stenvinkel, Karolina KublickieneAbstract
Background
Cardiovascular risk remains high after kidney transplantation, reflecting pre-transplant early vascular aging. Arterial stiffness generally improves, but the trajectory of microvascular endothelial function, and its dependence on recipient’s biological sex and donor matching, is unclear.
Methods
In 71 living-donor kidney transplant recipients, microvascular endothelial function (reactive hyperemia index, lnRHI) and arterial stiffness (augmentation index at 75 bpm, AI@75) were measured before transplantation and at a median of 24.6 months. Forty-six of their donors were assessed identically before donation, providing a healthy reference of the same sex. Resistance arteries from 37 recipients and 46 living donors underwent wire myography.
Results
AI@75 improved overall (−5.7%; P = 0.003), whereas microvascular function declined in men but not women (male ΔlnRHI −0.149, P = 0.002; sex × time interaction β = −0.19, P = 0.026), stable in direction across eleven specifications including tacrolimus exposure and graft function. The greater AI@75 improvement with sex-matched transplantation (P = 0.020) did not survive adjustment for baseline stiffness (P = 0.32). Ex vivo, endothelial relaxation showed no detectable sex difference in recipients (P = 0.83) or donors (P = 0.94), whereas passive stiffness was higher in female recipients (P = 0.048).
Conclusions
After living-donor kidney transplantation, arterial stiffness improved in both sexes while microvascular endothelial function declined in men and not in women. Referenced to healthy donors of the same sex, arterial stiffness in men remained abnormal at follow-up. Sex-matched transplantation conferred no independent vascular benefit. These findings are exploratory and require confirmation in larger cohorts.