title: The urinary proteome and metabonome differ from normal in adults with mitochondrial disease.
abstract: We studied the extent and nature of renal involvement in a cohort of 117 adult patients with mitochondrial disease, by measuring urinary retinol-binding protein (RBP) and albumin; established markers of tubular and glomerular dysfunction, respectively. Seventy-five patients had the m.3243A>G mutation and the most frequent phenotypes within the entire cohort were 14 with MELAS, 33 with MIDD, and 17 with MERRF. Urinary RBP was increased in 29 of 75 of m.3243A>G patients, whereas albumin was increased in 23 of the 75. The corresponding numbers were 16 and 14, respectively, in the 42 non-m.3243A>G patients. RBP and albumin were higher in diabetic m.3243A>G patients than in nondiabetics, but there were no significant differences across the three major clinical phenotypes. The urine proteome (mass spectrometry) and metabonome (nuclear magnetic resonance) in a subset of the m.3243A>G patients were markedly different from controls, with the most significant alterations occurring in lysosomal proteins, calcium-binding proteins, and antioxidant defenses. Differences were also found between asymptomatic m.3243A>G carriers and controls. No patients had an elevated serum creatinine level, but 14% had hyponatremia, 10% had hypophosphatemia, and 14% had hypomagnesemia. Thus, abnormalities in kidney function are common in adults with mitochondrial disease, exist in the absence of elevated serum creatinine, and are not solely explained by diabetes.
authors.affiliation: Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hall
authors.affiliation: Laboratory of Mass Spectrometry and Proteomics, Institute of Protein Biochemistry-CNR, Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Vilasi
authors.affiliation: Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia-Perez
authors.affiliation: South West Thames Institute for Renal Research, St Helier University Hospitals, Surrey, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Lapsley
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Alston
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, University College London Institute of Neurology, London, UK.
authors.forename: Robert D S
authors.initials: RD
authors.lastname: Pitceathly
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Schaefer
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.affiliation: Division of Medicine, Institute for Liver & Digestive Health, University College London, London, UK.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Beaumont
authors.affiliation: Division of Medicine, Institute for Liver & Digestive Health, University College London, London, UK.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Hsuan
authors.affiliation: Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary, University of London, London, UK.
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Cutillas
authors.affiliation: Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.affiliation: Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: UCL Centre for Nephrology, Royal Free Hospital, London, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Unwin
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Grainne S
authors.initials: GS
authors.lastname: Gorman
authors.affiliation: UCL Institute of Child Health, London, UK.
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Medical Research Council Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, University College London Institute of Neurology, London, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000652:urine; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D002135:Calcium-Binding Proteins / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D003638:Deafness / Q000150:complications / Q000235:genetics / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000652:urine; D006579:Heterozygote; D006801:Humans; D007010:Hyponatremia / Q000209:etiology; D017674:Hypophosphatemia / Q000209:etiology; D007674:Kidney Diseases / Q000150:complications / Q000652:urine*; D017241:MELAS Syndrome / Q000150:complications / Q000235:genetics / Q000652:urine; D017243:MERRF Syndrome / Q000150:complications / Q000235:genetics / Q000652:urine; D008274:Magnesium / Q000097:blood; D055442:Metabolome; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications / Q000235:genetics* / Q000652:urine*; D009154:Mutation; D011506:Proteins / Q000378:metabolism; D020543:Proteome; D012343:RNA, Transfer; D012177:Retinol-Binding Proteins / Q000652:urine; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D011506:Proteins; D020543:Proteome; D012177:Retinol-Binding Proteins; C018589:lysosomal proteins; D012343:RNA, Transfer; D003404:Creatinine; D008274:Magnesium