Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

Klein, J., Buffin-Meyer, B., Boizard, F., Moussaoui, N., Lescat, O., Breuil, B., Fedou, C., Feuillet, G., Casemayou, A., Neau, E., Hindryckx, A., Decatte, L., Levtchenko, E., Raaijmakers, A., Vayssière, C., Goua, V., Lucas, C., Perrotin, F., Cloarec, S., Benachi, A., Manca-Pellissier, M.C., Delmas, H.L., Bessenay, L., Le Vaillant, C., Allain-Launay, E., Gondry, J., Boudailliez, B., Simon, E., Prieur, F., Lavocat, M.P., Saliou, A.H., De Parscau, L., Bidat, L., Noel, C., Floch, C., Bourdat-Michel, G., Favre, R., Weingertner, A.S., Oury, J.F., Baudouin, V., Bory, J.P., Pietrement, C., Fiorenza, M., Massardier, J., Kessler, S., Lounis, N., Auriol, F.C., Marcorelles, P., Collardeau-Frachon, S., Zürbig, P., Mischak, H., Magalhães, P., Batut, J., Blader, P., Saulnier Blache, J.S., Bascands, J.L., Schaefer, F., Decramer, S., Schanstra, J.P., BIOMAN consortium
Kidney International   99(3): 737-749 (Journal)
Registered Authors
Batut, Julie, Blader, Patrick
Congenital anomalies of the kidney and the urinary tract, amniotic fluid, infants, management, peptides, prediction, termination of pregnancy
MeSH Terms
  • Amniotic Fluid
  • Animals
  • Child
  • Female
  • Humans
  • Kidney/diagnostic imaging
  • Kidney Diseases*
  • Peptides
  • Pregnancy
  • Prospective Studies
  • Urinary Tract*
  • Urogenital Abnormalities*/diagnostic imaging
  • Zebrafish
32750455 Full text @ Kidney Int.
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 hold-out 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.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes