Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial

Abstract

Anhydramnios caused by early anuria is thought to be universally fatal due to pulmonary hypoplasia. Bilateral renal agenesis and early fetal renal failure leading to anhydramnios constitute early pregnancy renal anhydramnios (EPRA). There have been successful reports of amnioinfusions to promote lung growth in the setting of EPRA. Some of these successfully treated EPRA fetuses have survived the neonatal period, undergone successful dialysis, and subsequently received a kidney transplant. Conversely, there are no reports of untreated EPRA survivors. This early success of amnioinfusions to treat EPRA justifies a rigorous prospective trial. The objective of this study is to provide a review of what is known about fetal therapy for EPRA and describe the Renal Anhydramnios Fetal Therapy trial. We review the epidemiology, pathophysiology, and genetics of EPRA. Furthermore, we have performed systematic review of case reports of treated EPRA. We describe the ethical framework, logistical challenges, and rationale for the current single center (NCT03101891) and planned multicenter trial.

Fetal lower urinary tract obstruction: What should we tell the prospective parents?

“…The prognosis of stage IV LUTO is extremely poor and hence these patients are not suitable candidates for fetal intervention . Management usually involves palliative care but serial amnioinfusion may also be useful for intrauterine fetal renal failure …”

Prenatal regenerative fetoscopic interventions for congenital anomalies

“…Serial amnioinfusion, which involves repeated infusion of sterile warm saline or lactated Ringer’s solution to restore amniotic fluid, is indicated for stage IV LUTO (intrauterine fetal renal failure) that occurs spontaneously or after fetal VAS (in stage III LUTO), according to our protocol (ClinicalTrials.gov Identifiers: NCT03723564, NCT03101891133134138). It aims to prevent severe pulmonary hypoplasia and perinatal demise, working as a bridge to postnatal dialysis and renal transplantation 150151. However, ethical and clinical questions persist on its benefits and safety particularly because renal transplantation cannot usually be offered to children under 2 152.…”

“…However, ethical and clinical questions persist on its benefits and safety particularly because renal transplantation cannot usually be offered to children under 2 152. For this reason, serial amnioinfusion is still under investigation,151 and clinical trials are under way (ClinicalTrials.gov Identifiers: NCT03723564, NCT03101891).…”

Response to “Contemporary Outcomes of Patients with Isolated Bilateral Renal Agenesis with and without Fetal Intervention” by RAFT Investigators

“…The NICHD-funded prospective Renal Anhydramnios Fetal Therapy (RAFT) trial (NCT03101891) [3,4] is the "North American Fetal Therapy Network Collaborative … prospective study enrolling patients whose fetuses DOI: 10.1159/000509749 have BRA" to which we believe the authors refer. This trial is currently enrolling patients and is slated to include 35 fetuses with prenatally diagnosed BRA, with a primary outcome of neonatal respiratory survival to successful dialysis.…”