The impact of donor and recipient sex on kidney allograft survival in pediatric transplant recipients

Background Transplantation is widely considered the gold standard method of kidney replacement therapy. Despite compelling evidence for biological sexual dimorphisms, the role of donor and recipient sex matching in transplantation is undefined. Methods The UK historical cohort study explores the impact of donor and recipient sex on allograft survival, in children receiving their first deceased donor transplant. Nationwide registry data were collected for 1316 transplant procedures performed from January 1, 1999, to December 31, 2019. Results Male donor-male recipient transplantation occurred most frequently (35%), followed by female donor-male recipient (23%), male donor-female recipient (22%), and female donor-female recipient (20%). The median follow-up time was 7.03 years (IQR: 2.89-12.4 years), with a total of 10,326 person-years. Male donor-male recipients were associated with the highest 10-year kidney allograft survival (72.8% [95% CI 68.3-77.8]) and male donor-female recipients with the lowest (64% [95% CI 57.7-71.1]). Multivariable Cox regression demonstrated for male donor transplantation, the risk of kidney allograft failure was 1.46 times greater for female (compared to male) recipients, after adjusting for acquired recipient age, recipient/donor age at transplantation, mismatched HLA A/B/DR, waitlist time, cold ischemia time, CMV seropositivity, donor hypertension, and donor diabetes (HR 1.46 [95% CI. 1.06-2.01], p = 0.02). There was no evidence for an independent effect of donor or recipient sex in other combinations. Conclusion This study highlights the complex relationship between donor and recipient sex and pediatric kidney allograft survival, which require further mechanistic evaluation.