Trial offers hope for babies with fetal kidney failure

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 their fetus's survival after birth.

Now, new results of a completed, federally funded 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, funded by the National Institutes of Health (NIH), were published July 1 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. 

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 such that 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.

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 from 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 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 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. 

Two-year-old Levi Smith is a testament to the success of the treatment provided in the RAFT trial. At 20 weeks pregnant, his mother, Sarah Smith, was told she had the option to either abort her pregnancy or continue carrying Levi knowing he likely wouldn't survive long after birth. With amnioinfusion treatment, Levi is now "a fun, happy kid" receiving chronic dialysis, his mother says. "We still have a long road ahead of us, but I know he wouldn't be here without the RAFT trial." 

The researchers say they plan to continue a next phase of RAFT with the goal of reducing premature birth, a known complication of amnioinfusion treatment. The closer to full term infants are, 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 results of the trial also suggest that infants born after this intervention face substantial medical challenges independent of lung function, especially if they are born severely prematurely.