Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

Julie Klein, Bénédicte Buffin-Meyer, BIOMAN consortium, Franck Boizard, Nabila Moussaoui, Ophélie Lescat, Benjamin Breuil, Camille Fedou, Guylène Feuillet, Audrey Casemayou, Eric Neau, An Hindryckx, Luc Decatte, Elena Levtchenko, Anke Raaijmakers, Christophe Vayssière, Valérie Goua, Charlotte Lucas, Franck Perrotin, Sylvie CloarecAlexandra Benachi, Marie Christine Manca-Pellissier, Hélène Laurichesse Delmas, Lucie Bessenay, Claudine Le Vaillant, Emma Allain-Launay, Jean Gondry, Bernard Boudailliez, Elisabeth Simon, Fabienne Prieur, Marie Pierre Lavocat, Anne Hélène Saliou, Loic De Parscau, Laurent Bidat, Catherine Noel, Corinne Floch, Guylène Bourdat-Michel, Romain Favre, Anne Sophie Weingertner, Jean François Oury, Véronique Baudouin, Jean Paul Bory, Christine Pietrement, Maryse Fiorenza, Jérôme Massardier, Sylvie Kessler, Nadia Lounis, Françoise Conte Auriol, Pascale Marcorelles, Sophie Collardeau-Frachon, Karel Allegaert

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

Abstract

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-β4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Original languageEnglish
Pages (from-to)737-749
Number of pages13
JournalKidney International
Volume99
Issue number3
DOIs
Publication statusPublished - Mar 2021

Bibliographical note

Funding Information:
This work was financed in part by the French “Programme Hospitalier de Recherche Clinique” (10 138 01, RCB 2010-AO1151-38), the Fondation pour la Recherche Médicale (DEQ20170336759), and the Agence de la Biomédecine (METAPhOR Project). FS, EL, HM, JPS, and PZ were supported in part by the European Commission Seventh Framework Programme (FP7/2007-2013), Grant Agreement 305608 (EURenOmics). EL is supported by Research Foundation –Flanders (Grant 1801110N ). The funders had no role in this study.

Publisher Copyright:
© 2021 International Society of Nephrology

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