title: Evaluation of novel urinary renal biomarkers: biological variation and reference change values.
abstract: A number of novel urinary biomarkers have been identified and partially qualified for use as markers for renal injury in rats. We used two multiplex assays for these novel biomarkers to quantify biomarker concentration in serial urine collections from rats of both sexes administered varying concentrations of cisplatin. From these data, we calculate inter-individual variation and reference ranges from predose animals and intra-individual variation and reference change values from undosed control animals. The biomarkers evaluated are albumin, α glutathione s-transferase, glutathione S-transferase-yb1, lipocalin-2, kidney injury molecule-1, osteopontin, and renal papillary antigen 1. For any creatinine-corrected novel biomarkers, we found intra-individual variation to be no greater than 44% and inter-individual variation to be no greater than 46%. Reference change values for most corrected analytes (except osteopontin) were 50-100%, indicating that a >100% increase in analyte concentration between serial samples would be unlikely to be associated with inherent analytical or biological variation.
authors.affiliation: Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK. Mark.pinches@astrazeneca.com
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pinches
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Betts
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Bickerton
authors.forename: Laura
authors.initials: L
authors.lastname: Beattie
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Burdett
authors.forename: Helen T
authors.initials: HT
authors.lastname: Thomas
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Derbyshire
authors.forename: Michele
authors.initials: M
authors.lastname: Moores
authors.forename: Sally A
authors.initials: SA
authors.lastname: Price
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000652:urine; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000652:urine*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
chemical_list: D015415:Biomarkers; D003404:Creatinine; D002945:Cisplatin