Fetal Therapy for Bilateral Renal Agenesis (Renal Anhydramnios)
Direct Recommendation
Serial amnioinfusions represent the only potentially life-saving intervention for bilateral renal agenesis diagnosed before 26 weeks gestation, with the goal of preventing lethal pulmonary hypoplasia by restoring amniotic fluid volume. 1, 2
Understanding the Condition
Bilateral renal agenesis with anhydramnios before 26 weeks gestation—termed early pregnancy renal anhydramnios (EPRA)—has historically been considered universally fatal due to severe pulmonary hypoplasia that precludes ex utero survival. 1, 2 Without intervention, there are no reported survivors of untreated EPRA. 2
The pathophysiology is straightforward:
- Fetal anuria before 22 weeks leads to complete absence of amniotic fluid 1
- Prolonged anhydramnios prevents normal lung development 3
- The degree of pulmonary hypoplasia worsens with increasing duration of anhydramnios (correlation r = -0.75, p = 0.01 for cases >22 weeks) 3
- Earlier intervention is therefore critical—the sooner amnioinfusions begin, the better the potential lung development 3
The Intervention: Serial Amnioinfusions
What It Involves
Serial amnioinfusions involve weekly percutaneous instillation of fluid into the amniotic cavity to maintain fluid volume and promote fetal lung growth. 4, 1
Evidence of Efficacy
While no randomized trials exist, case reports demonstrate proof of concept:
- A 23-week EPRA case treated with weekly amnioinfusions delivered at 28 weeks; the neonate required minimal respiratory support and survived to 9 months on peritoneal dialysis 4
- Two additional cases successfully bridged to living-related kidney transplantation after prenatal amnioinfusions and neonatal peritoneal dialysis 5
- These represent the only documented survivors of bilateral renal agenesis 5, 2
The RAFT Trial
The Renal Anhydramnios Fetal Therapy (RAFT) trial (NCT03101891) is the first prospective multicenter study evaluating amnioinfusions for EPRA, with the primary outcome being neonatal survival to successful dialysis (≥14 days of catheter use). 1 This trial began enrollment in April 2020 across 9 North American Fetal Therapy Network centers. 1
Practical Implementation Algorithm
Eligibility Criteria
- Isolated bilateral renal agenesis diagnosed before 26 weeks gestation 1
- Anhydramnios (maximum vertical pocket <2 cm) 6
- Absence of other major structural anomalies 1
- Maternal age ≥18 years 1
Timing Considerations
Begin amnioinfusions as soon as feasible after diagnosis and before 22 weeks if possible, as pulmonary hypoplasia severity correlates directly with anhydramnios duration. 3 The earlier treatment starts, the greater the potential for lung development. 3
Procedure Protocol
- Weekly amnioinfusions until delivery 4
- Typical delivery occurs between 28-34 weeks gestation 4, 5
- Requires tertiary center with Level III NICU capability 7
- Multidisciplinary team must include maternal-fetal medicine, neonatology, and pediatric nephrology 8
Maternal Monitoring
- Serial blood pressure checks to detect mirror syndrome 7
- Fetal surveillance with biophysical profiles 6
- Assessment for procedure-related complications (infection, preterm labor, membrane rupture) 1
Critical Counseling Points
Realistic Expectations
Survival is not guaranteed—even with intervention, outcomes remain uncertain. 1, 2 However, without treatment, the condition is 100% fatal. 2
Neonatal Course
Survivors will require:
- Immediate peritoneal dialysis starting shortly after birth 4, 5
- Long-term dialysis as a bridge to kidney transplantation 5
- Lifelong immunosuppression after transplant 5
- Potential complications of end-stage renal disease from birth 1
Quality of Life Considerations
The burden of chronic kidney disease from birth, including daily peritoneal dialysis, multiple hospitalizations, and eventual transplantation with lifelong immunosuppression, must be explicitly discussed with families. 1 This is not a cure but a pathway to survival with significant medical complexity. 1
What NOT to Do
Common Pitfalls
- Do not delay referral to a fetal therapy center—earlier intervention correlates with better lung development 3
- Do not offer amnioinfusions outside a tertiary center with appropriate neonatal dialysis capabilities 7, 1
- Do not proceed without comprehensive genetic testing to exclude syndromic causes 7
- Do not underestimate the neonatal complexity—survival requires immediate access to pediatric nephrology and dialysis 4, 5
Contraindications to Intervention
- Diagnosis after 26 weeks gestation (outside current trial parameters) 1
- Presence of additional major structural anomalies 1
- Chromosomal abnormalities 7
- Maternal contraindications to serial procedures 1
Alternative: Expectant Management
For families declining intervention, expectant management with palliative care planning is appropriate. 1 The RAFT trial includes an observational arm for natural history documentation. 1 Without amnioinfusions, neonatal death from respiratory failure is inevitable. 2
Comparison to Other Conditions
This differs fundamentally from oligohydramnios with functioning kidneys, where delivery timing and surveillance are the primary concerns. 6 With bilateral renal agenesis, in utero intervention is the only option that offers any survival possibility. 2
The evidence base, while limited to case reports and an ongoing trial, represents the only documented pathway to survival for an otherwise uniformly lethal condition. 4, 5, 2