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Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

Julie Klein 1, 2 Bénédicte Buffin-Meyer 1, 2 Franck Boizard 1, 2 Nabila Moussaoui 1, 2 Ophélie Lescat 1, 2 Benjamin Breuil 1, 2 Camille Fedou 1, 2 Guylène Feuillet 1, 2 Audrey Casemayou 1, 2 Eric Neau 1, 2 An Hindryckx 3 Luc Decatte 3 Elena Levtchenko 4 Anke Raaijmakers 4 Christophe Vayssière 5 Valérie Goua 6 Charlotte Lucas 6 Franck Perrotin 7 Sylvie Cloarec 8 Alexandra Benachi 9 Marie-Christine Manca-Pellissier 10 Hélène Laurichesse Delmas 11 Lucie Bessenay 11 Claudine Le Vaillant 12 Emma Allain-Launay 12 Jean Gondry 13 Bernard Boudailliez 14 Elisabeth Simon 15 Fabienne Prieur 16 Marie-Pierre Lavocat 16 Anne-Hélène Saliou 17 Loic de Parscau 18 Laurent Bidat 19 Catherine Noel 19 Corinne Floch 20 Guylène Bourdat-Michel 21 Romain Favre 22 Anne-Sophie Weingertner 22 Jean-François Oury 23 Véronique Baudouin 23 Jean-Paul Bory 24 Christine Pietrement 24 Maryse Fiorenza Jérôme Massardier 25, 26 Sylvie Kessler 27 Nadia Lounis 28 Françoise Conte Auriol 28 Pascale Marcorelles 29 Sophie Collardeau-Frachon 30 Petra Zürbig 31 Harald Mischak 31, 32 Pedro Magalhães 33 Julie Batut 34 Patrick Blader 34 Jean-Sebastien Saulnier Blache 1, 2 Jean-Loup Bascands 35 Franz Schaefer 36 Stéphane Decramer 1, 2, 28, 37 Joost Schanstra 1, 2 
1 Equipe 7 Inserm U1048
I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
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.
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Contributor : Jean Sébastien Saulnier-Blache Connect in order to contact the contributor
Submitted on : Wednesday, June 23, 2021 - 11:50:15 AM
Last modification on : Saturday, June 25, 2022 - 3:40:10 AM
Long-term archiving on: : Friday, September 24, 2021 - 6:30:12 PM


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Julie Klein, Bénédicte Buffin-Meyer, Franck Boizard, Nabila Moussaoui, Ophélie Lescat, et al.. Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease. Kidney International, Nature Publishing Group, 2021, 99 (3), pp.737-749. ⟨10.1016/j.kint.2020.06.043⟩. ⟨inserm-03268524⟩



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