The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design
Authors: Buffin-Meyer Bénédicte , Klein Julie , van der Zanden Loes F M , Levtchenko Elena , Moulos Panogiotis , Lounis Nadia , Conte-Auriol Françoise , Hindryckx An , Wühl Elke , Persico Nicola , Oepkes Dick , Schreuder Michiel F , Tkaczyk Marcin , Ariceta Gema , Fossum Magdalena , Parvex Paloma , Feitz Wout , Olsen Henning , Montini Giovanni , Decramer Stéphane , Schanstra Joost P ,   the ANTENATAL Consortium, Hindryckx An , De Catte Luc , Vayssieres Christophe , Sartor Agnès , Groussolles Marion , Plard Christelle , Guerby Paul , Connan Laure , Morin Mathieu , Simon Elizabeth , Breaud Jean , Saliou Anne-Hélène , De Parscau Loic , Jay Nadine , Germouty Isabelle , Le Bouar Gwenaelle , Ryckewaert Amelie , Manca-Pellissier Marie-Christine , Merrot Thierry , Laurichesse Helene , Gallot Denis , Bessenay Lucie , Bidat Laurent , Boize Philippe , Winer Norbert , Allain-Launey Emma , Le Vaillant Claudine , Prieur Fabienne , Lavocat Marie-Pierre , Coatleven Frederic , Debromez Eric , Harembat Jérôme , Llanas Brigitte , Favre Romain , Moog Raphael , Zaloszyc Ariane , Massardier Jérôme , Demede Delphine , Perrotin Franck , Cloarec Sylvie , Vequeau-Goua Valérie , Descombes Emmanuelle , Boulot Pierre , Morin Denis , Fuchs Florent , Tenenbaum Julie , Ville Yves , Blanc Thomas , Heidet Laurence , Paris Anne , Dobremez Eric , Froute Marie-Françoise , Gondry Jean , Muszynski Charles , Haraux Elodie , Lobelle Fabienne , Chevreau Julien , Rosenblatt Jonathan , Baudoin Véronique , Deschenes Georges , Guigue Virginie , Amblard Florence , Bourdat-Michel Guylhène , Wühl Elke , Schaefer Franz , Elsässer Michael , Persico Nicola , Rossi Federica , Manzoni Gianantonio , De Marco Erika A , Montini Giovanni , Capone Valentina , Caforio Leonardo , Zaccara Antonio , Innocenzi Michele , Bagolan Pietro , Capozza Nicola , Castagnetti Marco , Mancini Mariangela , Oepkes Dick , van Scheltema Phebe Adama , Feitz Wout , Kortmann Barbara , Schreuder Michiel , Tkaczyk Marcin , Stańczyk Małgorzata , Szaflik Krzysztof , Wojtera Justyna , Krzeszowski Waldemar , Talar Tomasz , Pawłowska Barbara , Fortecka-Piestrzeniewicz Katarzyna , Olejniczak Dariusz , Ariceta Gema , Arevalo Silvia , Rodo Carlota , Fossum Magdalena , Lindgren Peter , Parvex Paloma , Chehade Hassib 
Published: July 2019

Abstract

Background
Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature.

Methods
Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in &gt;30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature.

Results
In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment.

Conclusions
Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.