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Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

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 conduc...

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Main Authors: Klein, Julie (Author) , Buffin-Meyer, Bénédicte (Author) , Boizard, Franck (Author) , Moussaoui, Nabila (Author) , Lescat, Ophélie (Author) , Breuil, Benjamin (Author) , Fedou, Camille (Author) , Feuillet, Guylène (Author) , Casemayou, Audrey (Author) , Neau, Eric (Author) , Hindryckx, An (Author) , Decatte, Luc (Author) , Levtchenko, Elena (Author) , Raaijmakers, Anke (Author) , Vayssière, Christophe (Author) , Goua, Valérie (Author) , Lucas, Charlotte (Author) , Perrotin, Franck (Author) , Cloarec, Sylvie (Author) , Benachi, Alexandra (Author) , Manca-Pellissier, Marie-Christine (Author) , Delmas, Hélène Laurichesse (Author) , Bessenay, Lucie (Author) , Le Vaillant, Claudine (Author) , Allain-Launay, Emma (Author) , Gondry, Jean (Author) , Boudailliez, Bernard (Author) , Simon, Elisabeth (Author) , Prieur, Fabienne (Author) , Lavocat, Marie-Pierre (Author) , Saliou, Anne-Hélène (Author) , De Parscau, Loic (Author) , Bidat, Laurent (Author) , Noel, Catherine (Author) , Floch, Corinne (Author) , Bourdat-Michel, Guylène (Author) , Favre, Romain (Author) , Weingertner, Anne-Sophie (Author) , Oury, Jean-François (Author) , Baudouin, Véronique (Author) , Bory, Jean-Paul (Author) , Pietrement, Christine (Author) , Fiorenza, Maryse (Author) , Massardier, Jérôme (Author) , Kessler, Sylvie (Author) , Lounis, Nadia (Author) , Auriol, Françoise Conte (Author) , Marcorelles, Pascale (Author) , Collardeau-Frachon, Sophie (Author) , Zürbig, Petra (Author) , Mischak, Harald (Author) , Magalhães, Pedro (Author) , Batut, Julie (Author) , Blader, Patrick (Author) , Saulnier Blache, Jean-Sebastien (Author) , Bascands, Jean-Loup (Author) , Schaefer, Franz (Author) , Decramer, Stéphane (Author) , Schanstra, Joost P. (Author) , Allegaert, Karel (Author) , Aubard, Yves (Author) , Basmaison, Odile (Author) , Benevent, Jean-Baptiste (Author) , Biquard, Florence (Author) , Champion, Gérard (Author) , Delbosc, Jean-Marie (Author) , Eckart, Philippe (Author) , Froute, Marie-Françoise (Author) , Gaucherand, Pascal (Author) , Groussolles, Marion (Author) , Guigonis, Vincent (Author) , Hougas, Blandine (Author) , Le Bouar, Gwenaelle (Author) , Martin, Alain (Author) , Martin, Sophie (Author) , Maupin-Hyvonnet, Mariannick (Author) , Merveille, Marina (Author) , Mousty, Eve (Author) , Nobili, François (Author) , Ryckewaert, Amelie (Author) , Sartor, Agnes (Author) , Taque, Sophie (Author) , Winer, Norbert (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Kidney international
Year: 2021, Volume: 99, Issue: 3, Pages: 737-749
ISSN:1523-1755
DOI:10.1016/j.kint.2020.06.043
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.kint.2020.06.043
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0085253820308942
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Author Notes:Julie Klein, Bénédicte Buffin-Meyer, 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 Cloarec, Alexandra 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, Petra Zürbig, Harald Mischak, Pedro Magalhães, Julie Batut, Patrick Blader, Jean-Sebastien Saulnier Blache, Jean-Loup Bascands, Franz Schaefer, Stéphane Decramer and Joost P. Schanstra ; for the BIOMAN consortium

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520 |a 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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SRT |a KLEINJULIEAMNIOTICFL2021 

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