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Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis

Abstract

We analyzed urinary polypeptides from individuals with neonatal ureteropelvic junction (UPJ) obstruction to predict which individuals with this condition will evolve toward obstruction that needs surgical correction. We identified polypeptides that enabled diagnosis of the severity of obstruction and validated these biomarkers in urine collected in a prospective blinded study. Using these noninvasive biomarkers, we were able to predict, several months in advance and with 94% precision, the clinical evolution of neonates with UPJ obstruction.

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Figure 1: Urinary profiles and UPJ obstruction–specific urinary biomarkers.
Figure 2: Membership of urinary proteomic patterns of 36 newborns with intermediate UPJ obstruction and the clinical outcome of these individuals 9 months after group membership prediction.

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Acknowledgements

This work was supported by a grant from the Clinical Research Hospital Program from the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2004) and sponsored by the University Hospital of Toulouse for regulatory and ethic submission. J.P.S. was supported by Inserm and the “Direction Régional de la Recherche” (Centre Hospitalier Universitaire de Toulouse) under the Interface program. We would like to thank P. Koester for his technical assistance during the MS/MS experiments.

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Correspondence to Joost P Schanstra.

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Competing interests

Harald Mischak is founder and co-owner of Mosaiques Diagnostics, which developed the CE-MS technology and software solutions utilized in this manuscript.

Supplementary information

Supplementary Fig. 1

DMSA scintigraphy one year after surgery of an OP patient showing severely degraded function of one of the kidneys. (PDF 894 kb)

Supplementary Fig. 2

MS/MS (LIFT TOF-TOF) spectra of four potential biomarkers from human urine for UPJ-obstruction. (PDF 1584 kb)

Supplementary Table 1

Classification of different UPJ-obstruction patients. (PDF 20 kb)

Supplementary Table 2

Polypeptides of good discriminatory value identified by mass and migration time. (PDF 17 kb)

Supplementary Table 3

All UPJ patients used in the study as well as the healthy controls. (PDF 767 kb)

Supplementary Tables 4

Raw mass spectrometry data file (pivot table). (XLS 31990 kb)

Supplementary Methods (PDF 46 kb)

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Decramer, S., Wittke, S., Mischak, H. et al. Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis. Nat Med 12, 398–400 (2006). https://doi.org/10.1038/nm1384

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