Urinary proteome analysis in congenital bilateral hydronephrosis

Abstract

Objective. A proteomics strategy was applied to map protein changes in urine after relief of congenital bilateral hydronephrosis to identify proteins correlated with the pathophysiological processes in congenital obstructive nephropathy as potential urinary biomarkers. Material and methods. Urine samples from 10 infants with bilateral abnormal drainage from the kidneys were collected at the time of relief from obstruction, and after 2 and 4 weeks. Proteomics techniques were used on samples from three patients for identification of protein changes between the three time-points, and enzyme-linked immunosorbent assay (ELISA) was used on samples from all 10 patients for validation of five selected proteins. Results. Mass spectrometry quantified 315 protein hits, out of which 33 proteins showed significantly changed urinary excretion between the time-points. Validation by ELISA showed high urinary excretion of fibrinogen, plasminogen, transthyretin and transferrin at the time of relief from obstruction, followed by a significant reduction. In contrast, Tamm–Horsfall protein exhibited the reverse pattern. Conclusion. Using a mass spectrometry-based proteomics approach, this study identified 33 proteins related to congenital bilateral hydronephrosis, and pinpointed a panel of five proteins consistently linked to this congenital kidney disorder as potential urinary biomarkers.

Key Words::

• bilateral hydronephrosis
• mass spectrometry
• proteomics
• urinary biomarker

Acknowledgements

The authors would like to thank the technicians at the Water and Salt Research Center, Skejby, Denmark, for expert technical assistance, Mogens Erlandsen (Department of Biostatistics, University of Aarhus, Denmark) for statistical assistance and Professor Jørgen Thorup (Department of Pediatric Surgery, Rigshospitalet, Copenhagen, Denmark) for the inclusion of one patient. Funding was provided by the A. P. Møller Foundation for the Advancement of Medical Science, The John and Birthe Meyer Foundation, and the Dagmar Marshall Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.