title: Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury.
abstract: The capacities of urinary trefoil factor 3 (TFF3) and urinary albumin to detect acute renal tubular injury have never been evaluated with sufficient statistical rigor to permit their use in regulated drug development instead of the current preclinical biomarkers serum creatinine (SCr) and blood urea nitrogen (BUN). Working with rats, we found that urinary TFF3 protein levels were markedly reduced, and urinary albumin were markedly increased in response to renal tubular injury. Urinary TFF3 levels did not respond to nonrenal toxicants, and urinary albumin faithfully reflected alterations in renal function. In situ hybridization localized TFF3 expression in tubules of the outer stripe of the outer medulla. Albumin outperformed either SCr or BUN for detecting kidney tubule injury and TFF3 augmented the potential of BUN and SCr to detect kidney damage. Use of urinary TFF3 and albumin will enable more sensitive and robust diagnosis of acute renal tubular injury than traditional biomarkers.
authors.affiliation: Department of Investigative Laboratory Sciences, Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Daniel
authors.initials: D
authors.lastname: Holder
authors.forename: Josef S
authors.initials: JS
authors.lastname: Ozer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Villarreal
authors.forename: Paul
authors.initials: P
authors.lastname: Shughrue
authors.forename: Shu
authors.initials: S
authors.lastname: Shi
authors.forename: David J
authors.initials: DJ
authors.lastname: Figueroa
authors.forename: Holly
authors.initials: H
authors.lastname: Clouse
authors.forename: Ming
authors.initials: M
authors.lastname: Su
authors.forename: Nagaraja
authors.initials: N
authors.lastname: Muniappa
authors.forename: Sean P
authors.initials: SP
authors.lastname: Troth
authors.forename: Wendy
authors.initials: W
authors.lastname: Bailey
authors.forename: John
authors.initials: J
authors.lastname: Seng
authors.forename: Amy G
authors.initials: AG
authors.lastname: Aslamkhan
authors.forename: Douglas
authors.initials: D
authors.lastname: Thudium
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sistare
authors.forename: David L
authors.initials: DL
authors.lastname: Gerhold
mesh_terms: D000419:Albuminuria / Q000652:urine*; D000818:Animals; D054316:Biomarkers, Pharmacological / Q000652:urine*; D015780:Carbapenems / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D005839:Gentamicins / Q000633:toxicity; D006651:Histocytochemistry; D057889:Iridoid Glycosides; D039823:Iridoids / Q000633:toxicity; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D016015:Logistic Models; D009479:Neuropeptides / Q000652:urine*; D012372:ROC Curve; D051381:Rats; D000071165:Trefoil Factor-3
chemical_list: D054316:Biomarkers, Pharmacological; D015780:Carbapenems; D005839:Gentamicins; D057889:Iridoid Glycosides; D039823:Iridoids; D009479:Neuropeptides; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3; C007834:genipin; D002945:Cisplatin
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