title: A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.
abstract: Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.
  
  
  
  Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.
  
  
  
  Forty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.
  
  
  
  A number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers.
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Landolt-Marticorena
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Stephenie D
authors.initials: SD
authors.lastname: Prokopec
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Canada.
authors.forename: Stacey
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Canada.
authors.forename: Babak
authors.initials: B
authors.lastname: Noamani
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Canada.
authors.forename: Dennisse
authors.initials: D
authors.lastname: Bonilla
authors.affiliation: Department of Nephrology, University Health Network, University of Toronto Faculty of Medicine, Toronto, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Reich
authors.affiliation: Department of Nephrology, University Health Network, University of Toronto Faculty of Medicine, Toronto, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Scholey
authors.affiliation: Department of Pathology, University of Toronto, Toronto General Hospital, University Health Network, Toronto, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Avila-Casado
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval and Department of Medicine, CHU de Québec - Université Laval, Quebec City, Canada.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: Krembil Research Institute, University Health Network, Toronto, Canada. jwither@uhnres.utoronto.ca.|Division of Rheumatology, University Health Network, Toronto, Canada. jwither@uhnres.utoronto.ca.|Departments of Medicine and Immunology, University of Toronto, Toronto, Canada. jwither@uhnres.utoronto.ca.|Toronto Western Hospital, 1E-420, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. jwither@uhnres.utoronto.ca.
authors.forename: Joan
authors.identifier: 0000-0001-5961-9228
authors.initials: J
authors.lastname: Wither
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000652:urine*; D008181:Lupus Nephritis / Q000652:urine*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Glomerulonephritis; Renal biopsy; Systemic lupus erythematosus; Urinary biomarkers