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Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

2020; Elsevier BV; Volume: 99; Issue: 3 Linguagem: Inglês

10.1016/j.kint.2020.06.043

1523-1755

Julie Klein, Bénédicte Buffin‐Meyer, Franck Boizard, Nabila Moussaoui, Ophélie Lescat, Benjamin Breuil, C. Fédou, Guylène Feuillet, Audrey Casemayou, Eric Neau, An Hindryckx, Luc De Catte, Elena Levtchenko, Anke Raaijmakers, Christophe Vayssière, Valérie Goua, C. Lucas, F. Perrotin, Sylvie Cloarec, Alexandra Benachi, Marie-Christine Manca-Pellissier, Hélène Laurichesse Delmas, Lucie Bessenay, Claudine Le Vaillant, Emma Allain‐Launay, J. Gondry, B. Boudailliez, Elisabeth Simon, Fabienne Prieur, Marie‐Pierre Lavocat, A.‐H. Saliou, L de Parscau, Laurent Bidat, Catherine Noël, Corinne Floch, Guylène Bourdat-Michel, R. Favre, A.-S. Weingertner, Jean‐François Oury, Véronique Baudouin, Jean‐Paul Bory, Christine Piètrement, Maryse Fiorenza, J. Massardier, S. Kessler, Nadia Lounis, Françoise Auriol, Pascale Marcorelles, Sophie Collardeau‐Frachon, Petra Zürbig, Harald Mischak, Pedro Magalhães, Julie Batut, Patrick Blader, Jean-Sébastien Saulnier Blache, Jean‐Loup Bascands, Franz Schaefer, Stéphane Decramer, Joost P. Schanstra, Karel Allegaert, Y. Aubard, Odile Basmaison, J Benevent, F. Biquard, Gérard Champion, Jean-Marie Delbosc, Philippe Eckart, Marie-Françoise Froute, P. Gaucherand, Marion Groussolles, Vincent Guigonis, Blandine Hougas, G. Le Bouar, Alain Martin, Sophie Martin, Mariannick Maupin-Hyvonnet, M. Merveille, E. Mousty, François Nobili, Amélie Ryckewaert, Agnès Sartor, Sophie Taque, Norbert Winer,

Infant Nutrition and Health

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.