Format:
13
ISSN:
1523-1755
Content:
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.
Note:
Additional BIOMAN consortium collaborators: Karel Allegaert, Yves Aubard, Odile Basmaison, Jean-Baptiste Benevent, Florence Biquard, Gérard Champion, Jean-Marie Delbosc, Philippe Eckart, Marie-Françoise Froute, Pascal Gaucherand, Marion Groussolles, Vincent Guigonis, Blandine Hougas, Gwenaelle Le Bouar, Alain Martin, Sophie Martin, Mariannick Maupin-Hyvonnet, Marina Merveille, Eve Mousty, François Nobili, Amelie Ryckewaert, Agnes Sartor, Sophie Taque, Norbert Winer
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Veröffentlicht online: 1 August 2020
,
Gesehen am 26.10.2021
In:
Kidney international, New York, NY : Elsevier, 1972, 99(2021), 3 vom: März, Seite 737-749, 1523-1755
In:
volume:99
In:
year:2021
In:
number:3
In:
month:03
In:
pages:737-749
In:
extent:13
Language:
English
DOI:
10.1016/j.kint.2020.06.043
URL:
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