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

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.

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Acknowledgement

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

Funding

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).

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Correspondence to Joost P. Schanstra.

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

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Supplementary Table 1

Normalized abundance of each of the ~5616 fetal urinary peptides in each sample. (XLSX 1115 kb)

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Buffin-Meyer, B., Tkaczyk, M., Stańczyk, M. et al. A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves. Pediatr Nephrol 35, 469–475 (2020). https://doi.org/10.1007/s00467-019-04390-9

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Keywords

  • Urinary proteome analysis
  • Prenatal
  • Prediction
  • Outcome
  • Chronic kidney disease
  • Rare disease