Risk of Pregnancy Complications in Living Kidney Donors: A Systematic Review and Meta-analysis

The criterion standard for management of end-stage kidney disease is kidney donation. However, kidney donation remains a complicated medical issue for the donor, as mid- and long-range complications are possible as a result of the procedure. Because significant proportions of kidney donors are women of childbearing age, an expanding interest exists regarding potential concerns about subsequent pregnancy complications. The aim of this meta-analysis is to gather and evaluate available literature knowledge in order to understand the potential that kidney donation increases the risk of hypertensive pregnancy disorders, perinatal mortality, and other obstetric complications. The study population consisted of childbearing-aged women both with and without history of living kidney donation. Adverse pregnancy outcome rates were compared between nondonors and donors. Outcomes of interest included preeclampsia, gestational diabetes, gestational hypertension, preterm birth (<37 weeks), cesarean delivery, low birthweight (<2500 g), and fetal death. Studies eligible for the meta-analysis included prospective and retrospective observational studies, whereas cross-sectional studies, uncontrolled studies, case series, review articles, conference abstracts, animal studies, and in vitro studies were excluded. From the 5 qualifying studies, the following information was extracted for a total of 23,970 women (23,540 nondonors and 430 donors): country, year of publication, exclusion criteria, study design, sample size, data source, participants' age at pregnancy, years of donation, and time interval between donation and pregnancy. Results of the analysis comparing donors and nondonors indicated that living kidney donation has an association with significantly higher rates of gestational hypertension, higher preeclampsia risk, and significantly higher risk for preterm birth. Rates of cesarean deliveries did not differ between groups, and low birthweight rates were estimated to be similar for both groups as well. Strengths of the study include its comprehensive literature search in 5 databases without any restrictions. As the same time, limitations of this meta-analysis included its basis on a small number of studies (although the overall sample size of participants was large). Because of a lack of study stratification for preeclampsia cases based on severity and onset, no conclusions can be drawn in regard to the effects of donation on the incidence of preterm preeclampsia, although this is associated with fetal growth restriction and worse neonatal outcomes. In addition, the study lacked reporting of aspirin potentially administered during the second and third trimesters of pregnancy, thus blurring its detectable effects in this population. Moreover, the outcome of low birthweight was not examined in the context of gestational age at delivery, which warrants further field studies on whether kidney donation predisposes small-for-gestational age infants. Finally, impact of the time interval between donation and pregnancy on clinical outcomes remains currently undetermined. Ultimately, increased rates of preeclampsia, gestational hypertension, and preterm birth in subsequent pregnancies exist after living kidney donation (although absolute risk for this remains below 10%). Low to moderate existing evidence quality requires future studies for verification of these outcomes and a need for the construction of quantitative tools that enable the individualized assessment of long-term donor risks.