Kidney Donors' Pregnancies Show 11.9% Hypertension Hospitalizations vs 8.3%, but Relatives May Skew the Comparison

Most pregnancies after living kidney donation are uncomplicated. That is the main finding of a matched cohort study in JAMA, presented this week at the American Society of Nephrology's Kidney Week in Denver. It also found more hospitalizations for high blood pressure disorders among donors. The rate was 11.9 percent of donor pregnancies versus 8.3 percent among comparable women who never donated.

Researchers at Western University and the London Health Sciences Centre Research Institute in Ontario led the work. They used linked provincial health data from Ontario, British Columbia and Alberta. It followed 385 pregnancies in 252 women aged 18 to 48 who donated a kidney between July 1992 and August 2021. The comparison group had 1,540 pregnancies in 1,535 women who never donated. Matching covered delivery date, age, prior pregnancies, income and other factors. Nondonors with any of 35 conditions that would rule out donation were excluded.

A modest gap in hospitalizations for hypertension

The primary outcome was hospitalization for gestational hypertension, preeclampsia or eclampsia. The relative risk was 1.51, with a 95 percent confidence interval of 1.10 to 2.08. In absolute terms the gap is 3.6 percentage points. Preeclampsia or eclampsia taken alone had a relative risk of 1.52, but its interval, 1.01 to 2.29, only just clears 1.

Amit Garg, the senior author and a nephrologist at London Health Sciences Centre, said these disorders were generally first recorded close to term. Fewer than 2 percent of pregnancies in either group had one recorded before 34 weeks. Gestational diabetes, caesarean delivery, premature birth, neonatal intensive care admission, serious maternal complications and postpartum hemorrhage were comparable between the groups.

A second signal, still unconfirmed

Babies born to donors were more likely to be small for gestational age, meaning a birth weight below the 10th percentile. The rates were 13.8 percent versus 7.9 percent, relative risk 1.86 (1.37 to 2.52). In post hoc analyses the gap held at stricter cutoffs. Below the 5th percentile it was 6.5 percent versus 3.6 percent, and below the 3rd, 4.7 percent versus 1.9 percent.

Garg said this may be the most unexpected result, because earlier attention had centered on hypertension and preeclampsia. It was also one of 12 secondary outcomes examined, so chance is a possible explanation, and the authors say it needs confirmation in other studies. Garg offered one mechanism as a hypothesis. Reduced kidney function may impair the kidney's normal adaptation to pregnancy, which could affect placental development and blood flow. The authors cited a mouse model with one kidney removed that showed similar placental changes. That is animal data, not proof of the pathway in people.

Why donors' relatives complicate the comparison

In Ontario, 63.9 percent of donors were first-degree relatives of the person who received the kidney. Few women in the comparison group would have a parent or sibling with kidney failure, so inherited susceptibility could contribute to the difference. Garg said genetic confounding "remains possible," though he argued the observations make it less likely to explain the whole association. Post hoc analyses by donor-recipient relatedness had too few events to confirm or rule out a difference.

Some features of the design point the other way. All donors had normal kidney measures at evaluation. Pregnancies occurred a mean of 5.6 years after donation, and women with a hypertensive disorder of pregnancy before entering the cohort were excluded. The main outcome counts hospitalizations, so milder cases managed outside a hospital are not captured by it.

What the counseling conversation now rests on

Garg has counseled more than 1,000 prospective kidney donors over two decades, according to the Western and LHSCRI release. In that release he said the decision is not only about a donor's health today but about "what life might look like years down the road," including whether they hope to have children.

The new study expands on an earlier Ontario analysis of 131 pregnancies after donation, which gave less precise estimates. For counseling, Garg suggested conveying that most postdonation pregnancies are uncomplicated while noting the modestly higher observed frequency of gestational hypertension and preeclampsia. For donors who later develop hypertension, reduced kidney function or albuminuria, he suggested individualized counseling with clinicians experienced in both kidney disease and high-risk pregnancy.

One limit on this report: the JAMA paper itself did not load for automated requests. The figures here come from the Western and LHSCRI release, Healio's account of the Kidney Week presentation, and an HCPLive interview with Garg. All three trace to the same single study.