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Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

J. Klein 1 B. Buffin-Meyer 1 F. Boizard 1 Nabila Moussaoui 1 O. Lescat 1 B. Breuil 1 C. Fedou 1 G. Feuillet 1 A. Casemayou 1 E. Neau 1 A. Hindryckx 2 L. Decatte 2 E. Levtchenko 3 A. Raaijmakers 3 C. Vayssière 4 V. Goua 5 C. Lucas 5 F. Perrotin 6 S. Cloarec 7 A. Benachi 8 M. C. Manca-Pellissier 9 H. L. Delmas 10 L. Bessenay 10 C. Le Vaillant 11 E. Allain-Launay 11 Jean Gondry 12 Bernard Boudailliez 13 E. Simon 14 F. Prieur 15 M. P. Lavocat 15 A. H. Saliou 16 L. de Parscau 17 L. Bidat 18 C. Noel 18 C. Floch 19 G. Bourdat-Michel 20 R. Favre 21 A. S. Weingertner 21 J. F. Oury 22 V. Baudouin 22 J. P. Bory 23 C. Pietrement 23 M. Fiorenza 24 J. Massardier 25 S. Kessler 26 N. Lounis 27 F. C. Auriol 27 P. Marcorelles 28 S. Collardeau-Frachon 29, 30 P. Zürbig 31 H. Mischak 31, 32 P. Magalhães 31 J. Batut 33 P. Blader 33 J. S. Saulnier Blache 1 J. L. Bascands 34 F. Schaefer 35 S. Decramer 36, 37, 38, 1 J. P. Schanstra 36, 1
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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Submitted on : Wednesday, May 26, 2021 - 3:05:25 PM
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J. Klein, B. Buffin-Meyer, F. Boizard, Nabila Moussaoui, O. Lescat, et al.. Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease. Kidney International, Nature Publishing Group, 2020, 99 (3), pp.737-749. ⟨10.1016/j.kint.2020.06.043⟩. ⟨inserm-03237054⟩



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