Kidney Week

Abstract: SA-OR045

Amniotic Fluid Peptide Biomarkers for In Utero Prediction of Postnatal Renal Function in CAKUT

Session Information

• Pediatric Nephrology and Developmental Biology
  November 04, 2017 | Location: Room 285, Morial Convention Center
  Abstract Time: 05:18 PM - 05:30 PM

Category: Developmental Biology and Inherited Kidney Diseases

• 403 Pediatric Nephrology

Authors

• Klein, Julie, Inserm U1048, Toulouse, France

Julie Klein, PhD

• Buffin-Meyer, Benedicte, Inserm U1048, Toulouse, France

Benedicte Buffin-Meyer,

• Boizard, Franck, Inserm U1048, Toulouse, France

Franck Boizard,

• Magalhães, Pedro, Mosaiques Diagnostics GmbH, Hannover, Germany

Pedro Magalhães,

• Zürbig, Petra, Mosaiques Diagnostics GmbH, Hannover, Germany

Petra Zürbig,

• Breuil, Benjamin, Inserm U1048, Toulouse, France

Benjamin Breuil,

• Levtchenko, Elena N., University Hospitals Leuven, Herent, Belgium

Elena N. Levtchenko,

• Hindryckx, An, University Hospitals Leuven, Herent, Belgium

An Hindryckx,

• Nadia, Lounis, Hopital des Enfants, Toulouse, France

Lounis Nadia,

• Auriol, Francoise, Hopital des Enfants, Toulouse, France

Francoise Auriol,

• Bascands, Jean-loup, Inserm U1048, Toulouse, France

Jean-loup Bascands,

• Decramer, Stéphane, Hopital des Enfants, Toulouse, France

Stéphane Decramer,

• Schanstra, Joost, Inserm U1048, Toulouse, France

Joost Schanstra,

Group or Team Name

• Bioman-consortium

Background

Clinical management of fetuses with bilateral CAKUT is hampered by the lack of methods able to predict evolution towards kidney failure. Here we explored the amniotic fluid (AF) peptidome of 152 bilateral CAKUT pregnancies in order to identify biomarkers predictive of disease progression.

Methods

Using capillary electrophoresis coupled to mass spectrometry, comparison of the AF peptidome from 32 fetuses with normal postnatal renal function at 2 years and 18 fetuses with early renal failure allowed the identification of 59 differentially abundant peptides, including fragments from extracellular matrix proteins, osteopontin, proSAAS or thymosin beta-4.

Results

Modelling the 59 peptides into a random forest classifier combined with clinical features (AF volume and the age of the fetus at the time of sampling) predicted the renal outcome at 2 years in a separate validation cohort of 68 CAKUT fetuses with 89% sensitivity, 98% specificity and a positive likelihood ratio of 44. Next, we used the classifier to discriminate 34 CAKUT fetuses subjected to termination of pregnancy (TOP) but where fetopathology analysis either failed to demonstrate severe renal damage or was absent or inconclusive. The classifier scores suggested that TOP without severe renal damage could have been avoided in 80% of the cases. In addition, the classifier predicted 55% of absent/inconclusive fetopathology as having severe postnatal outcome and 45% with normal function. Taking into account likelihood ratio and sensitivity, we can speculate that approximately 40% of these fetuses with non-interpretable fetopathology were subjected to TOP while most likely evolving to normal postnatal renal function.

Conclusion

We believe that identification of the 59 AF peptide biomarkers is a significant step forward for antenatal prediction of the postnatal renal function outcome in CAKUT fetuses and should be of great help for early prenatal counsellingand improved clinical management of CAKUT pregnancies, hence alleviating the psychological burden imposed on the parents. [Equal contribution JK and BBM].

Funding

• Private Foundation Support