title: A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function.
abstract: The Predictive Safety Testing Consortium's first regulatory submission to qualify kidney safety biomarkers revealed two deficiencies. To address the need for biomarkers that monitor recovery from agent-induced renal damage, we scored changes in the levels of urinary biomarkers in rats during recovery from renal injury induced by exposure to carbapenem A or gentamicin. All biomarkers responded to histologic tubular toxicities to varied degrees and with different kinetics. After a recovery period, all biomarkers returned to levels approaching those observed in uninjured animals. We next addressed the need for a serum biomarker that reflects general kidney function regardless of the exact site of renal injury. Our assay for serum cystatin C is more sensitive and specific than serum creatinine (SCr) or blood urea nitrogen (BUN) in monitoring generalized renal function after exposure of rats to eight nephrotoxicants and two hepatotoxicants. This sensitive serum biomarker will enable testing of renal function in animal studies that do not involve urine collection.
authors.affiliation: Department of Investigative Laboratory Sciences, Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania, USA.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Ozer
authors.forename: Frank
authors.initials: F
authors.lastname: Dieterle
authors.forename: Sean
authors.initials: S
authors.lastname: Troth
authors.forename: Elias
authors.initials: E
authors.lastname: Perentes
authors.forename: André
authors.initials: A
authors.lastname: Cordier
authors.forename: Pablo
authors.initials: P
authors.lastname: Verdes
authors.forename: Frank
authors.initials: F
authors.lastname: Staedtler
authors.forename: Andreas
authors.initials: A
authors.lastname: Mahl
authors.forename: Olivier
authors.initials: O
authors.lastname: Grenet
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Roth
authors.forename: Daniel
authors.initials: D
authors.lastname: Wahl
authors.forename: François
authors.initials: F
authors.lastname: Legay
authors.forename: Daniel
authors.initials: D
authors.lastname: Holder
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Erdos
authors.forename: Katerina
authors.initials: K
authors.lastname: Vlasakova
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Nagaraja
authors.initials: N
authors.lastname: Muniappa
authors.forename: Tom
authors.initials: T
authors.lastname: Forest
authors.forename: Holly K
authors.initials: HK
authors.lastname: Clouse
authors.forename: Spencer
authors.initials: S
authors.lastname: Reynolds
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Bailey
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Thudium
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Topper
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Skopek
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Sina
authors.forename: Warren E
authors.initials: WE
authors.lastname: Glaab
authors.forename: Jacky
authors.initials: J
authors.lastname: Vonderscher
authors.forename: Gérard
authors.initials: G
authors.lastname: Maurer
authors.forename: Salah-Dine
authors.initials: SD
authors.lastname: Chibout
authors.forename: Frank D
authors.initials: FD
authors.lastname: Sistare
authors.forename: David L
authors.initials: DL
authors.lastname: Gerhold
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000097:blood / Q000378:metabolism / Q000652:urine; D001806:Blood Urea Nitrogen; D015780:Carbapenems / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005839:Gentamicins / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000175:diagnosis*; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D054316:Biomarkers, Pharmacological; D015780:Carbapenems; D055316:Cystatin C; D005839:Gentamicins; D003404:Creatinine
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