Donating a Kidney Could Lead to Later Pregnancy Complications

— But most post-donation pregnancies proceed without major issues

DENVER -- Donating a kidney was associated with a higher risk of gestational hypertensive disorders during subsequent pregnancy, though complications were rare overall, according to a Canadian matched cohort study.

Among women with singleton pregnancies of at least 20 weeks' gestation, 11.9% of kidney donors experienced the primary composite outcome -- hospitalization with a diagnosis of gestational hypertension, preeclampsia, or eclampsia -- compared with 8.3% of matched nondonors (risk ratio [RR] 1.51, 95% CI 1.10-2.08).

Kidney donation before pregnancy was also associated with higher rates of small-for-gestational-age births (13.8% vs 7.9%; RR 1.86, 95% CI 1.37-2.52), reported Amit X. Garg, MD, PhD, of the London Health Sciences Centre in Ontario, and colleagues.

The findings were presented at the American Society of Nephrology Kidney Weekopens in a new tab or window annual meeting and simultaneously published in JAMAopens in a new tab or window.

"Donor candidates who may become pregnant should be counseled that donation may be associated with a modestly higher chance of developing gestational hypertension or preeclampsia," Garg told MedPage Today. "For donors who do become pregnant, it is important that they have access to appropriate prenatal care, with attention to blood pressure and other features of hypertensive disorders of pregnancy."

However, he emphasized that the vast majority of pregnancies following donation proceed without major issues. "These hypertensive disorders were generally first recorded close to term," he noted. "Fewer than 2% of pregnancies in either group had the outcome first recorded before 34 weeks."

The findings are particularly relevant given the demographics of donors: approximately 65% of living kidney donors are female, and roughly 75% are of childbearing age at the time of donation.

"Living kidney donation provides an extraordinary benefit to people with kidney failure, and the decision to donate requires thoughtful consideration of both the benefits to the recipient and the long-term health of the donor," Garg said. "These findings should be viewed in that context; a desire to become pregnant in the future should not, by itself, exclude someone from becoming a living kidney donor."

The study aligns with prior research that prompted 2017 international guidelines advising clinical teams to counsel donor candidates on the potential risks for gestational hypertensive disorders. The observed association is biologically plausible, as pregnancy demands significant increases in renal blood flow and glomerular filtration.

"In an experimental model, unilaterally nephrectomized mice had impaired kidney adaptation to pregnancy, with abnormal placental development, placental hypoperfusion, and an antiangiogenic state," Garg and co-authors wrote. "Placental dysfunction is a recognized pathway shared by hypertensive disorders of pregnancy and impaired fetal growth."

While the elevated risk for gestational hypertension was expected based on prior literature, Garg noted that the higher rate of small-for-gestational-age births (birth weight below the 10th percentile) was less anticipated. "Because this was one of several secondary outcomes examined, it requires confirmation in other studies," he said.

For this population-based study, the researchers used administrative healthcare data across three Canadian provinces. A total of 385 pregnancies among 252 kidney donors (mean age at cohort entry 27.8 years) were matched 1:4 with 1,540 pregnancies among 1,535 nondonors (mean age 27.0 years) for factors including delivery date, maternal age, time between cohort entry and delivery, parity, and income quintile.

Eleven other secondary outcomes showed no clear difference between groups, including gestational hypertension; preeclampsia or eclampsia; early-onset gestational hypertension or preeclampsia; severe maternal morbidity; cesarean delivery; postpartum hemorrhage; gestational diabetes; composite of preterm birth or low birth weight; neonatal intensive care unit admission; stillbirth; and neonatal death.

Subgroup analyses showed consistent risk ratios for the primary outcome across parity (nulliparous vs parous) and time elapsed since cohort entry (<5 years vs ≥5 years). However, the risk ratio was larger in magnitude among women ages 35 or older at delivery (14.3% of donors vs 7.6% of nondonors; RR 1.99, 95% CI 1.18-3.33) compared with those under age 35 (10.7% vs 8.7%, respectively; RR 1.41, 95% CI 0.93-2.15).

The authors noted several limitations to their study, including potential residual genetic confounding since many donors are related to their recipients and may share a genetic susceptibility to kidney dysfunction. Other limitations included a lack of administrative data regarding maternal body mass index, blood pressure measurements, or medication use during pregnancy.