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J Proteome Res. 2013 May 3;12(5):2013-21. doi: 10.1021/pr301200e. Epub 2013 Apr 2.

The identification of new biomarkers for identifying and monitoring kidney disease and their translation into a rapid mass spectrometry-based test: evidence of presymptomatic kidney disease in pediatric Fabry and type-I diabetic patients.

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1
Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, Guilford Street, London, WC1N 1EH, UK.

Abstract

Using label-free quantative proteomics, we have identified 2 potential protein biomarkers that indicate presymptomatic kidney disease in the urine of pediatric patients with type-I diabetes and Fabry disease (n = 20). Prosaposin and GM2 activator protein (GM2AP) were observed to be elevated in the urine of these patient groups compared to age- and sex-matched controls. These findings were validated by development of a rapid MRM-based tandem mass spectrometry test. Prosaposin was observed to be both significantly elevated in the urine of patients with Fabry disease compared to controls (p = 0.02) and reduced after 12 months enzyme replacement therapy (ERT, p = 0.01). Similarly, GM2AP concentrations were observed to be significantly higher compared to controls in the diabetic group (p = 0.049) and the pretreatment Fabry group (p = 0.003). In addition, this observed to be reduced significantly in the Fabry group following 12 months of ERT (p = 0.01). The process of detection of the biomarkers, development into a test and implications for monitoring patients and treatment are discussed.

PMID:
23464927
DOI:
10.1021/pr301200e
[Indexed for MEDLINE]

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