| Literature DB >> 20458319 |
Josef S Ozer1, Frank Dieterle, Sean Troth, Elias Perentes, André Cordier, Pablo Verdes, Frank Staedtler, Andreas Mahl, Olivier Grenet, Daniel R Roth, Daniel Wahl, François Legay, Daniel Holder, Zoltan Erdos, Katerina Vlasakova, Hong Jin, Yan Yu, Nagaraja Muniappa, Tom Forest, Holly K Clouse, Spencer Reynolds, Wendy J Bailey, Douglas T Thudium, Michael J Topper, Thomas R Skopek, Joseph F Sina, Warren E Glaab, Jacky Vonderscher, Gérard Maurer, Salah-Dine Chibout, Frank D Sistare, David L Gerhold.
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.Entities:
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Year: 2010 PMID： 20458319 DOI： 10.1038/nbt.1627
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908