Comparison of the amniotic fluid and fetal urine peptidome for biomarker discovery in renal developmental disease

Camille Fédou,Françoise Muller,Stéphane Decramer,Benjamin Breuil,Igor Golovko,Joost P Schanstra,Petra Zürbig,Pedro Magalhães,Julie Klein,Sophie Dreux,Bénédicte Buffin-Meyer

doi:10.1038/s41598-020-78730-3

Abstract

Production of amniotic fluid (AF) is view as predominately driven by excretion of fetal urine (FU). However, the origin of AF peptides, often considered as potential biomarkers of developmental diseases, has never been investigated. Here, we evaluated the FU origin of AF peptides and if the AF peptide content can be used as a surrogate of FU. The abundance of endogenous peptides was analyzed by capillary electrophoresis coupled to mass spectrometry in 216 AF and 64 FU samples. A total of 2668 and 3257 peptides was found in AF and FU respectively. The AF peptidome largely overlapped with the FU peptidome, ranging from 54% in the second pregnancy trimester to 65% in the third trimester. Examination of a subset of 16 paired AF and FU samples revealed that 67 peptides displayed a significant positively correlated abundance in AF and FU, strongly suggesting that their presence in AF was directly associated to FU excretion. As proof-of-concept we showed that measuring the AF abundance of these 67 peptides of FU origin allowed prediction of postnatal renal survival in fetuses with posterior urethral valves. These results demonstrate that the AF peptidome can be considered as a good surrogate of the FU peptidome.

Highlights

Production of amniotic fluid (AF) is view as predominately driven by excretion of fetal urine (FU)
We identified and validated 12 peptides in fetal urine (FU) that predicted in utero postnatal renal survival in fetuses with developmental renal disease[10,11]
A total of 2668 peptides were detected in AF whereas 3257 peptides were found in FU (Fig. 1A)

Summary

Introduction

Production of amniotic fluid (AF) is view as predominately driven by excretion of fetal urine (FU). As proof-of-concept we showed that measuring the AF abundance of these 67 peptides of FU origin allowed prediction of postnatal renal survival in fetuses with posterior urethral valves These results demonstrate that the AF peptidome can be considered as a good surrogate of the FU peptidome. Using a prospective multicentre cohort including 178 patients, we identified an AF signature containing 98 peptides that predicted with high accuracy the postnatal renal outcome in fetuses having bilateral kidney malformations (CAKUT for congenital anomalies of the kidney and urinary tract), outperforming predictions based on currently used clinical methods[14] The presence of such markers in AF is interesting since AF sampling is less invasive than FU collection

Methods

Results

Conclusion