Prenatal therapy improves outcomes in fetal renal failure

A multicenter clinical trial has demonstrated that serial prenatal amnioinfusions can improve survival among fetuses with renal failure and anhydramnios by promoting fetal lung development, offering a potential treatment pathway for a condition that has historically been considered uniformly fatal after birth. Investigators caution, however, that survival represents only the first milestone for these children, who require extensive multidisciplinary care throughout infancy and early childhood.^1,2

Results from the Renal Anhydramnios Fetal Therapy (RAFT) trial, recently published in JAMA, evaluated outcomes among pregnant patients carrying fetuses with kidney failure caused by bilateral renal agenesis or other severe abnormalities of the kidneys and urinary tract. The study found that repeated prenatal replacement of amniotic fluid supported fetal lung development, allowing many infants to survive long enough to begin treatment for end-stage kidney disease.

How does fetal renal failure lead to anhydramnios?

Amniotic fluid plays a critical role in fetal development. By approximately 16 to 20 weeks' gestation, most amniotic fluid is produced from fetal urine. When the fetal kidneys or urinary tract fail to develop normally, urine production is absent or severely impaired, resulting in anhydramnios. Without sufficient amniotic fluid, fetal lungs cannot develop adequately, leading to pulmonary hypoplasia and historically little chance of survival after delivery.

As Meredith Atkinson, MD, MHS, pediatric nephrologist at Johns Hopkins Children's Center and co-lead of the RAFT study, explained, "Without enough amniotic fluid, the fetus's lungs cannot develop properly, often leading to severe respiratory issues after birth."

During an interview with Contemporary Pediatrics, Atkinson explained that the trial was designed to determine whether replacing the missing fluid throughout pregnancy could restore normal lung development despite persistent kidney failure.

"The RAFT trial is a trial that looked at whether introducing fluid into the amniotic sac periodically during pregnancy in patients who had fetal anhydramnios due to renal failure could result in adequate lung development."

She noted that the study demonstrated that amnioinfusions successfully addressed the pulmonary consequences of fetal renal failure, although they did not eliminate the underlying kidney disease.

What did the RAFT trial find about serial amnioinfusions?

The current report evaluated 32 pregnant women who began serial amnioinfusions before 26 weeks' gestation. More than 90% delivered live-born infants, although all were born prematurely before 37 weeks. Overall, 65.5% survived to 2 weeks of age and tolerated placement of dialysis access, the first step toward long-term kidney replacement therapy.

Researchers concluded that serial amnioinfusions can safely promote fetal lung development and improve survival in pregnancies complicated by fetal renal failure.

Atkinson said one of the most important findings was confirmation that replacement fluid itself—not necessarily native amniotic fluid—is sufficient to support fetal lung development.

"These findings show that even though the replacement fluid, which was often just normal saline fluid or a very common medically used fluid called lactated ringers, even though it wasn't amniotic fluid, it was adequate to promote lung development. So this confirms the role of the fluid in lung development."

She added that many clinicians and families may not realize how dependent lung development becomes on fetal urine during the second trimester.

"Many people don't know that after about 16 weeks of gestation, the majority of amniotic fluid is fetal urine."

Although pulmonary survival improved substantially, kidney disease remained a major determinant of outcomes. During the interview, Atkinson explained that many infants experienced complications after birth despite successful lung development.

"We found that there were many complications in these infants, so that while a large proportion, more than half of the infants survived to two weeks of life in the NICU and placement of dialysis access, fewer than half survived to go home from the hospital due to those complications."

She noted that among infants who were discharged home, kidney transplantation became an achievable long-term goal.

What should pediatricians know about caring for survivors?

For pediatricians, Atkinson emphasized that survival after fetal therapy is only the beginning of a medically complex journey.

"One thing that pediatricians should keep in mind is that most of these babies, in addition to having complications of end-stage kidney disease and being on dialysis... will often have been born prematurely."

Prematurity contributes substantially to ongoing morbidity. Although lung development is improved by amnioinfusions, infants may still experience chronic lung disease related to early delivery. Pediatricians should also anticipate developmental challenges resulting from both prematurity and chronic kidney disease.

Atkinson recommended careful developmental follow-up throughout infancy and early childhood.

"Neurodevelopmental evaluations would be important. Early services for any developmental delays would be important."

The study also identified neonatal and infantile stroke as a relatively frequent complication among survivors, creating additional risks for seizures and neurodevelopmental impairment. While dialysis management remains the responsibility of pediatric nephrologists, community pediatricians are likely to oversee routine developmental surveillance, coordinate specialty referrals, and monitor overall health between subspecialty visits.

How will the RAFT 2 trial build on these findings?

Investigators are now focusing on reducing one of the trial's greatest challenges: prematurity. Because repeated amnioinfusions require multiple needle insertions into the amniotic sac, they increase the risk of preterm rupture of membranes and preterm labor.

According to Atkinson, improving gestational age at delivery may be one of the most effective ways to improve survival.

"One of the best things in terms of resilience for these complicated infants is that they're born at later gestation at a higher birth weight, which allows them to withstand all of the challenges they'll face in the NICU."

RAFT 2 will also focus on reducing neonatal complications through closer monitoring for stroke, improved blood pressure management, and refinements in neonatal intensive care.

Beyond improving clinical outcomes, investigators hope the next phase of the trial will strengthen prenatal counseling. Atkinson said one of the greatest strengths of the original RAFT trial was its multidisciplinary approach, which included maternal-fetal medicine specialists, fetal surgeons, neonatologists, pediatric nephrologists, transplant specialists, and palliative care teams.

"One of the key takeaways I hope people have is that it's really important for prenatal counseling reasons to have families meet with a broad array of both pre and postnatal care teams."

She also emphasized that palliative care should be viewed as an important source of family support rather than solely end-of-life care, helping families understand treatment options, develop birth plans, and prepare for the long-term medical needs of a surviving child.

The investigators believe the findings establish an important foundation for future fetal therapy research. As Ahmet Baschat, MB BCh, BAO, director of the Johns Hopkins Center for Fetal Therapy, stated in the press release, "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."

References

1. John Hopkins Medicine. Study Shows Improved Survival Rates for Some Babies With Life-threatening Fetal Disorder. July 8, 2026. Accessed July 23, 2026. https://www.newswise.com/articles/study-shows-improved-survival-rates-for-some-babies-with-life-threatening-fetal-disorder/?sc=dwrecomm&xy=10069478&wt=dw_r_09072026

2. Miller JL, Baschat AA, Johnson A, et al. Neonatal survival after serial amnioinfusions for anhydramnios due to fetal kidney failure: the RAFT clinical trial. JAMA. Published online July 1, 2026. doi:10.1001/jama.2026.8568.