Interpreting Kidney Donor Pregnancy Signals, With Amit Garg, MD, PhD

Small for gestational age births and shared donor-recipient genetics complicate the picture of pregnancy after living kidney donation.

Investigators behind a new Canadian study of pregnancy after living kidney donation are weighing why donors had more small for gestational age (SGA) births than matched nondonors, and whether shared genetics with recipients could play a role.¹

The matched cohort study, presented at American Society of Nephrology (ASN) Kidney Week 2026 by Amit X. Garg, MD, PhD, and published simultaneously in JAMA, spanned 3 provinces and also found a modest increase in hypertensive disorders of pregnancy among donors.¹

How Did the Study Compare Donors and Nondonors?

Using linked administrative health databases from Ontario, British Columbia, and Alberta, investigators compared 385 pregnancies in 252 living kidney donors with 1,540 matched pregnancies in 1,535 nondonors.¹ To reflect donors’ healthier baseline profile, nondonors with any of 35 conditions that would preclude donation were excluded. Pregnancies were matched 1:4 on delivery date, maternal age, time from cohort entry to delivery, parity, and income.¹

The primary outcome, hospitalization with gestational hypertension, preeclampsia, or eclampsia, occurred in 11.9% of donor pregnancies vs 8.3% of nondonor pregnancies (risk ratio [RR], 1.51; 95% CI, 1.10-2.08).¹ More than 88% of donor pregnancies were unaffected, and rates of other outcomes, including severe maternal morbidity, preterm birth or low birth weight, and neonatal intensive care admission, were similar between groups.¹

Why Might Small for Gestational Age Births Have Been More Common in Donor Pregnancies?

Among 12 secondary outcomes, SGA birth, defined as birth weight below the 10th percentile, occurred in 13.8% of donor pregnancies vs 7.9% of nondonor pregnancies (RR, 1.86; 95% CI, 1.37-2.52).¹ In post hoc analyses, the association persisted at stricter thresholds, including birth weight below the fifth percentile (6.5% vs 3.6%) and the third percentile (4.7% vs 1.9%).¹

“One possibility is chance, particularly given the number of secondary outcomes we examined. At the same time, there is biological plausibility,” said Garg, professor of medicine, epidemiology and biostatistics at Western University, nephrologist at London Health Sciences Centre, and corresponding author of the study, in an interview with HCPLive.

Garg explained that reduced kidney function may impair normal renal adaptation to pregnancy and, in turn, may affect placental development and blood flow. In the paper, investigators cited an experimental model in which mice with 1 kidney removed showed impaired kidney adaptation to pregnancy, with abnormal placental development and placental hypoperfusion.¹ According to Garg, the finding warrants evaluation and confirmation in future studies.

Could Genetics Explain the Pregnancy Risks Seen in Kidney Donors?

Investigators flagged residual genetic confounding as a limitation. In Ontario, where donor-recipient relationship data were available, 63.9% of donors were first-degree relatives of their recipients.¹ Garg noted that few nondonors would be expected to have a first-degree relative with kidney failure, so inherited susceptibility could contribute to the observed association. Post hoc analyses, limited by small event counts, could neither confirm nor rule out a difference in risk by relatedness.¹

Garg pointed to several observations that reduce this concern. All donors had normal measures of kidney health at evaluation, and pregnancies occurred a mean of 5.6 years after donation.¹ By design, individuals with a recorded hypertensive disorder of pregnancy before cohort entry were excluded.¹ In Canada, individuals with these complications would generally not be accepted as donors while still of childbearing age, he added.

“So certainly, genetic confounding remains possible, but these observations make it less likely to fully explain the observed association,” Garg said.

Editor’s Note: Garg reported no relevant disclosures.

References

1. Wang C, Naylor KL, McArthur E, et al. Pregnancy outcomes after living kidney donation. JAMA. Published online October 22, 2026. doi:10.1001/jama.2026.21737

2. Garg AX. Pregnancy outcomes after living kidney donation. Presented at: American Society of Nephrology Kidney Week 2026; October 22, 2026; Denver, CO. Abstract TH-OR117.