Prenatal fluid infusions offer new hope for fetuses with severe kidney failure

For years, the diagnosis came like a door slamming shut. A pregnant woman at her second-trimester ultrasound learns that her fetus's kidneys are not developing, or are blocked, or are absent entirely. The kidneys make urine, and by the middle of pregnancy, urine becomes the primary source of amniotic fluid—the cushioning liquid that lets lungs expand and develop. Without it, a baby's lungs cannot form properly. After birth, respiratory failure follows almost inevitably. The prognosis was blunt: your child will not survive.

That calculus has shifted. A completed clinical trial, funded by the National Institutes of Health and led by Johns Hopkins Medicine, shows that some of these pregnancies can now result in children who live, breathe, and grow. The Renal Anhydramnios Fetal Therapy trial—known as RAFT—enrolled pregnant women at 13 centers across the United States beginning before 26 weeks of gestation. The intervention was straightforward in concept but unprecedented in application: doctors injected replacement fluid mimicking amniotic fluid directly into the womb, repeatedly, to give the fetus's lungs the space and stimulus they needed to develop. The results, published in JAMA on July 1, show that more than 90 percent of the 32 pregnancies in the latest cohort resulted in live births, though most came early. Nearly two-thirds of those infants survived to two weeks of age and were able to tolerate the placement of surgical access for dialysis—the machinery that would filter their blood and manage their kidney failure for the rest of their lives.

The condition itself is rare but devastating. Anhydramnios occurs when fetal kidneys, ureters, bladder, or urethra fail to develop properly, preventing the production or passage of urine. Some cases involve bilateral renal agenesis, a complete absence of both kidneys. Others stem from urinary tract obstruction or other developmental failures. By 16 to 20 weeks of pregnancy, healthy fetuses produce 90 percent or more of their amniotic fluid through urine. That fluid does more than cushion; it delivers nutrients, hormones, and other factors essential to lung development. Without it, the lungs remain underdeveloped—a condition called pulmonary hypoplasia—and newborns cannot breathe on their own.

The RAFT trial's approach was to artificially restore that fluid. Pregnant women received serial amnioinfusions—injections of synthetic amniotic fluid into the amniotic sac—designed to stimulate lung expansion and development. The goal was not to cure the kidney failure; that would require a transplant or lifelong dialysis. The goal was to buy the lungs time to grow. Meredith Atkinson, a pediatric nephrologist at Johns Hopkins Children's Center and co-lead of the study, explained the logic: without adequate amniotic fluid, fetal lungs cannot develop, often resulting in severe respiratory problems after birth. The infusions aimed to prevent that cascade.

The results represent a fundamental shift in what is possible. In the group with causes of kidney failure other than bilateral renal agenesis, 32 pregnant women underwent the treatment. More than 90 percent delivered live infants, though prematurely—before 37 weeks. Of those, 65.5 percent survived to two weeks of age and tolerated the placement of dialysis access. Two years later, a two-year-old named Levi Smith embodies the outcome. His mother, Sarah Smith, was told at 20 weeks that she could terminate the pregnancy or continue knowing her son would almost certainly die shortly after birth. She chose to enroll in RAFT. Today, Levi receives chronic dialysis and is, by his mother's account, a happy, active child. "We still have a long road ahead of us," she said, "but I know he wouldn't be here without the RAFT trial."

The trial is not without limitations. Premature birth remains a known complication of amnioinfusion treatment, and the earlier an infant arrives, the harder the transition to neonatal dialysis care becomes. The infants in the study faced substantial medical challenges beyond lung function, particularly those born severely early. Researchers are now launching RAFT 2, designed to reduce premature delivery and optimize the care these newborns receive after birth. Ahmet Baschat, director of the Johns Hopkins Center for Fetal Therapy, called the trial an important step forward in fetal medicine, one that demonstrates the value of a multidisciplinary approach and gives families facing this diagnosis something that did not exist before: a real choice, and real hope.