Proteomic Analysis of Amniotic Fluid to Predict Postnatal Renal Function in Fetuses With Renal and Urinary Tract Malformations (PAPER FACE)

The aim of this project is to validate a previously established amniotic fluid 98 peptide signature predictive of post-natal outcome in fetuses with congenital anomalies of the kidney and the urinary tract (CAKUT) in a "real" clinical context. It includes the feasibility of collecting, transporting and analyzing the amniotic fluid peptidome from clinical centers all over France and of providing the result in a clinically accepted time-frame. Therefore, this multicenter study will not only allow to determine the added value of such new prenatal test but also to ensure the feasibility of its introduction in the management of CAKUT pregnancies.

Study Overview

• Status: Recruiting
• Conditions: Kidney Diseases
• Intervention / Treatment: Other: Amniotic Fluid Proteomic Analysis Using Capillary Electrophoresis-Mass Spectrometry (CE-MS)

Detailed Description

CAKUT represent 20-30% of all inborn malformations. Whereas prognosis is generally favorable in unilateral disease, bilateral CAKUT are the predominant causes of chronic kidney disease (CKD) in childhood and account for ~50% of pediatric and young adult end stage renal disease (ESRD) cases. Current ultrasound- or amniotic fluid biochemistry-based prenatal clinical advice to parents expecting a child with bilateral CAKUT is far from accurate. This prognostic uncertainty of disease progression has particularly serious implications for parents confronted with the decision of continuation or elective termination of pregnancy. Such uncertainty has led to documented situations where half of the cases of severe bilateral CAKUT for whom termination of pregnancy was considered but not performed had normal postnatal renal function. In the case parents decide to continue the pregnancy, knowledge of the precise outcome would allow anticipating dialysis, transplantation or palliative care. 98 peptide signature have been identified in amniotic liquid that predicted with high sensitivity and specificity postnatal kidney function in fetuses with CAKUT (Klein, Buffin-Meyer et al., Kidney Int 2021).

The aim of the current project is to validate this signature in an independent multicenter French study and determine added value and feasibility of its introduction in the routine management of CAKUT pregnancies.

After the discovery of a CAKUT pregnancy in an associated French center and approval and informed consent of the parents, part of the amniotic fluid (~ 1 mL) that is routinely collected for chromosomal anomalies is transferred to the research laboratory Inserm U1297 in Toulouse. The peptide content of the amniotic fluid is analyzed allowing the evaluation of the abundance of the 98 peptides of the signature. It will result in a risk score for developing severe kidney failure before the age of 2 years, postnatally. This score will be communicated by the clinicians from Toulouse responsible for the project to the clinicians of the center requesting the analysis.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas SIMON; Phone Number: 05 34 55 84 58; Email: simon.t@chu-toulouse.fr
• Study Contact Backup: Name: Nadège Algans; Phone Number: +33 05 61 77 72 04; Email: algans.n@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France, 31059
    • Recruiting
    • Children Hospital
    • Contact: Thomas SIMON; Phone Number: +33 05 34 55 84 58; Email: simon.t@chu-toulouse.fr
    • Principal Investigator: Thomas SIMON

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All fetuses with bilateral renal development anomalies with structural changes in the parenchyma, with or without associated urinary tract anomalies;
• Signed informed consent of the mother
• Non-opposition of the father.

Exclusion Criteria:

• Unilateral abnormality of renal development
• Any pregnancy for which amniocentesis may represent a risk for the fetus or the mother
• Twin pregnancies
• Pregnant woman protected by law (guardianship, curatorship)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Proteomic-Based Prediction of Postnatal Kidney Function in Fetuses with Bilateral CAKUT

Other: Amniotic Fluid Proteomic Analysis Using Capillary Electrophoresis-Mass Spectrometry (CE-MS); This intervention consists of analyzing the amniotic fluid proteome using capillary electrophoresis coupled with mass spectrometry (CE-MS). The goal is to evaluate a predefined 98-peptide signature that predicts postnatal kidney function in fetuses with bilateral congenital anomalies of the kidney and urinary tract. Unlike standard prenatal assessments based on ultrasound and fetal biochemistry, this method provides a molecular-based prognostic tool to improve decision-making regarding pregnancy management and neonatal care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of the test in the evaluation of renal survival (need for dialysis) and patient survival at 2 years of life.	Renal survival is defined as the absence of end-stage renal disease (ESRD) requiring dialysis by 2 years of age. Patient survival is defined as the child being alive at 2 years. Renal function is assessed through clinical follow-up, including serum creatinine measurements and estimated glomerular filtration rate (eGFR) using the Schwartz formula. Dialysis initiation is determined based on standard clinical criteria for ESRD. Survival status is confirmed through medical records and follow-up visits. This outcome aims to validate the predictive value of the 98-peptide amniotic fluid signature for postnatal kidney function in CAKUT fetuses.	2 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of the test in the evaluation of postnatal renal function estimated by the Schwartz formula and his serum creatinine	Schwartz formula which is based on the patient's height (T, in cm) and his serum creatinine (Creat, in µmol/L) (T*36.5/Creat)	At months 1, 6, 12, and 24 postnatally
Severity score result rendering time	measure of the delay to give the result to the investigator site	up to 2 weeks after sample collection

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2025
• Primary Completion (Estimated): December 20, 2029
• Study Completion (Estimated): December 20, 2029

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prognosis; renal function; Antenatal; proteomic analysis; fetal bilateral nephropathies; renal ultrasound
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases
• Other Study ID Numbers: RC31/24/0291; ID-RCB : 2024-A01612-45 (Other Identifier: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No