A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function

被引：158

作者：

Ozer, Josef S. ^{[1
]}

Dieterle, Frank ^{[2
]}

Troth, Sean ^{[3
]}

Perentes, Elias ^{[2
]}

Cordier, Andre ^{[2
]}

Verdes, Pablo ^{[2
]}

Staedtler, Frank ^{[2
]}

Mahl, Andreas ^{[2
]}

Grenet, Olivier ^{[2
]}

Roth, Daniel R. ^{[2
]}

Wahl, Daniel ^{[2
]}

Legay, Francois ^{[2
]}

Holder, Daniel ^{[4
]}

Erdos, Zoltan ^{[1
]}

Vlasakova, Katerina ^{[1
]}

Jin, Hong ^{[1
]}

Yu, Yan ^{[1
]}

Muniappa, Nagaraja ^{[3
]}

Forest, Tom ^{[1
]}

Clouse, Holly K. ^{[5
]}

Reynolds, Spencer ^{[1
]}

Bailey, Wendy J. ^{[1
]}

Thudium, Douglas T. ^{[1
]}

Topper, Michael J. ^{[1
]}

Skopek, Thomas R. ^{[1
]}

Sina, Joseph F. ^{[1
]}

Glaab, Warren E. ^{[1
]}

Vonderscher, Jacky ^{[2
]}

Maurer, Gerard ^{[2
]}

Chibout, Salah-Dine ^{[2
]}

Sistare, Frank D. ^{[1
]}

Gerhold, David L. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Investigat Lab Sci, West Point, PA USA

[2] Novartis Inst BioMed Res, Basel, Switzerland

[3] Merck Res Labs, Dept Pathol, West Point, PA USA

[4] Merck Res Labs, Dept Biometr, West Point, PA USA

[5] Merck Res Labs, Dept Exploratory Toxicol, West Point, PA USA

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 05期

关键词：

CYSTATIN-C; KIDNEY INJURY; MOLECULE-1; CLUSTERIN; PROTEIN;

D O I：

10.1038/nbt.1627

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：486 / U146

页数：11

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