Womb fluid infusions help fetuses with kidney failure survive after birth

Women diagnosed early in pregnancy with a fetus lacking adequate kidney function to make the urine that serves as vital amniotic fluid have long faced virtually no chance of the fetus’s survival after birth.

Now, new results of a clinical trial investigating prenatal treatment for this condition, known as anhydramnios, conducted at the Johns Hopkins Center for Fetal Therapy and Johns Hopkins Children’s Center, show that some with the disorder have survived and thrived into toddlerhood owing to prenatal infusions of replacement fluid into the womb and kidney replacement therapy with dialysis after birth.

The latest findings from the Renal Anhydramnios Fetal Therapy (RAFT) trial are published in JAMA. Amniotic fluid is the liquid cushion for fetuses in the womb. By 16 to 20 weeks of gestation, 90% or more of the fluid is made from the baby’s urine, providing nutrients, hormones and other factors critical to the normal development of the fetal lungs. Anhydramnios happens when the fetal kidneys, ureters, bladder or urethra fail to develop properly, interfering with the ability to make or pass urine.

Amnioinfusions stimulate lung development

The RAFT Trial was conducted at 13 centers across the U.S., including Johns Hopkins Medicine, which was the lead coordinating center. Enrolled patients received repeated injections of fluid mimicking amniotic fluid (amnioinfusions) into the amniotic sac, with the goal of stimulating lung development so newborns could be delivered with functioning lungs.

“Without enough amniotic fluid, the fetus’s lungs cannot develop properly, often leading to severe respiratory issues after birth,” says Meredith Atkinson, M.D., M.H.S., pediatric nephrologist at Johns Hopkins Children’s Center and co-lead of the RAFT study.

Survival gains in the trial

The RAFT trial enrolled patients with fetal kidney failure from either bilateral renal agenesis, which is failure of the kidneys to develop at all, or other causes, including fetal urinary tract obstruction. Results in patients with bilateral renal agenesis were published in December 2023, and the more recent publication reports outcomes in the group with all other causes of fetal kidney failure.

In the new report, 32 pregnant women underwent serial amnioinfusions beginning before 26 weeks’ gestation. More than 90% of the 32 pregnancies resulted in a live but premature birth before 37 weeks’ gestation. Some 65.5% of those infants survived to age 2 weeks and were able to tolerate placement of surgical dialysis access, the first step in treating their chronic kidney failure.

Researchers say the new study shows that the amnioinfusions can be a successful and safe treatment for pregnant women carrying fetuses with the condition.

The next challenge is prematurity

“The RAFT trial marks an important step forward in fetal therapy. Building on this work, the RAFT 2 study explores how serial amnioinfusions may offer a new treatment pathway for patients with fetal renal failure, highlighting the value of a multidisciplinary approach and helping families make more informed decisions in complex situations,” says Ahmet Baschat, M.B.B.CH., B.A.O., director of the Johns Hopkins Center for Fetal Therapy.

The researchers say they plan to continue the next phase of RAFT with the goal of reducing premature birth, a known complication of amnioinfusion treatment. The closer infants are to full term, the better prepared they will be to tolerate the challenges of neonatal dialysis care. Atkinson says other goals of the ongoing RAFT study include optimizing postnatal care, as the trial results also suggest that infants born after this intervention face substantial medical challenges independent of lung function, especially if they are born severely prematurely.

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Stephanie Baum

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