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A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves

  • Bénédicte Buffin-Meyer
  • Marcin Tkaczyk
  • Małgorzata Stańczyk
  • Benjamin Breuil
  • Justyna Siwy
  • Krzysztof Szaflik
  • Tomasz Talar
  • Justyna Wojtera
  • Waldemar Krzeszowski
  • Stéphane Decramer
  • Julie Klein
  • Joost P. SchanstraEmail author
Original Article

Abstract

Background

Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study.

Methods

Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m2 before 6 months of age or pre- or perinatal death.

Results

The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74–1.0) and an accuracy of 90% (95%CI 78–100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72–0.97) and an accuracy of 84% (95%CI 71–97).

Conclusions

This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.

Keywords

Urinary proteome analysis Prenatal Prediction Outcome Chronic kidney disease Rare disease 

Notes

Acknowledgement

SD and JPS are members of the European Reference Network for Rare Kidney Diseases (ERKNet)– Project ID No 739532.

Funding information

The study was supported by Polish Mothers Memorial Hospital Research Institute (internal grant number 2016/IV/54-GW), by the “Fondation pour la Recherche Médicale” (grant number DEQ20170336759) and by the “Agence de la Biomédecine” (METAPhOR project).

Compliance with ethical standards

Conflict of interest

JS is an employee of Mosaiques diagnostics GmbH (Hannover, Germany) that markets urinary peptide-based diagnostics products.

Supplementary material

467_2019_4390_MOESM1_ESM.xlsx (1.1 mb)
Supplementary Table 1 Normalized abundance of each of the ~5616 fetal urinary peptides in each sample. (XLSX 1115 kb)

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Copyright information

© IPNA 2019

Authors and Affiliations

  • Bénédicte Buffin-Meyer
    • 1
    • 2
  • Marcin Tkaczyk
    • 3
  • Małgorzata Stańczyk
    • 3
  • Benjamin Breuil
    • 1
    • 2
  • Justyna Siwy
    • 4
  • Krzysztof Szaflik
    • 5
  • Tomasz Talar
    • 6
  • Justyna Wojtera
    • 5
  • Waldemar Krzeszowski
    • 5
  • Stéphane Decramer
    • 1
    • 2
    • 7
    • 8
  • Julie Klein
    • 1
    • 2
  • Joost P. Schanstra
    • 1
    • 2
    Email author
  1. 1.Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic DiseaseToulouseFrance
  2. 2.Université Toulouse III Paul-SabatierToulouseFrance
  3. 3.Department of Pediatrics, Immunology and NephrologyPolish Mother’s Memorial Hospital Research InstituteLodzPoland
  4. 4.Mosaiques diagnostics GmbHHannoverGermany
  5. 5.Department of Genecology, Fertility and Fetal TherapyPolish Mother’s Memorial Hospital - Research InstituteLodzPoland
  6. 6.Department of NeonatologyPolish Mother’s Memorial Hospital - Research InstituteLodzPoland
  7. 7.Service de Néphrologie Pédiatrique, Hôpital des Enfants, CHU ToulouseToulouseFrance
  8. 8.Centre de Référence des Maladies Rénales Rares du Sud-Ouest (SORARE)ToulouseFrance

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