Introduction: Almost twice as many females donated a kidney in the United States between 1988-2021. Yet, detailed information regarding their long-term outcomes are sparse. Importantly, there has been no studies that addressed the possible contribution of pregnancy or gestational complications. Therefore, we compared mortality, cardiovascular disease (CVD), and development of hypertension, diabetes, proteinuria, reduced estimated glomerular filtration rate (eGFR) and kidney failure in 4,995 females and 3881 male donors.

Methods: We studied female donors in a retrospective cohort study of kidney donors who donated between 1963 to 2007 at three US transplant centers as a part of The Renal and Lung Living Donor Evaluation Study. Mortality, CVD, diabetes, hypertension, proteinuria and reduced eGFR for the entire cohort and for females after adjusting for pregnancy and gestational complications were studied using multivariable analysis.

Results: At 17.4±10.8 years after donation, 4.1% of female donors and 5.8% of male donors were deceased, aHR 0.53 (95% CI 0.37, 0.76), p = 0.001; 6.5% vs. 8.0% developed diabetes, aHR 0.98 (95% CI 0.71, 1.32), p = 0.88; and 32.5% vs. 42.5% developed hypertension, aHR 0.87 (95% CI 0.77, 0.97), p = 0.02. The multivariable risks of death, CVD and hypertension were higher in male donors. The risk of reduced eGFR, proteinuria and ESKD were, however, comparable in both sexes. A similar proportion of female and male donors developed eGFR < 30 mL/min/1.73m² or kidney failure; 1.6% vs. 1.9%, aHR 0.68 (95% CI 0.34, 1.35), p = 0.98 (Figure 1, Figure 2). Donors with pregnancies prior to donation and gestational complications (compared to nulliparous donors) were at increased risk for this composite outcome; aHR 4.02 (95% CI 1.24, 13.02), p=0.02 and aHR 6.06 (95% CI 1.59, 23.15), p= 0.01, respectively.

Conclusions: These results demonstrate that the overall risk of kidney failure is similar in female and male kidney donors. Pre-donation pregnancies and gestational complications were associated with a 4- to 6-fold increased risk of eGFR <30 mL/min/1.73m² or ESKD compared to those without prior pregnancies. Our results are at odds with these previous studies that stated that males are at an increased risk of CVD and faster progression to ESKD. We believe the difference may stem from accounting not only for post-donation events such as diabetes and hypertension but also for prior pregnancies and gestational complications.