title: 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.
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.
authors: Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, Guilford Street, London, WC1N 1EH, UK.
authors: Victoria
authors: V
authors: Manwaring
authors: Wendy E
authors: WE
authors: Heywood
authors: Robert
authors: R
authors: Clayton
authors: Robin H
authors: RH
authors: Lachmann
authors: Joan
authors: J
authors: Keutzer
authors: Peter
authors: P
authors: Hindmarsh
authors: Bryan
authors: B
authors: Winchester
authors: Simon
authors: S
authors: Heales
authors: Kevin
authors: K
authors: Mills
mesh_terms: D000293:Adolescent; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000652:urine; D002648:Child; D002853:Chromatography, Liquid; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000628:therapy / Q000652:urine*; D049289:G(M2) Activator Protein / Q000652:urine; D006801:Humans; D008297:Male; D011507:Proteinuria / Q000652:urine*; D020543:Proteome / Q000378:metabolism*; D012015:Reference Standards; D049231:Saposins / Q000652:urine; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D049289:G(M2) Activator Protein; D020543:Proteome; D049231:Saposins