Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury

被引：267

作者：

Dieterle, Frank ^{[1
]}

Perentes, Elias ^{[1
]}

Cordier, Andre ^{[1
]}

Roth, Daniel R. ^{[1
]}

Verdes, Pablo ^{[1
]}

Grenet, Olivier ^{[1
]}

Pantano, Serafino ^{[1
]}

Moulin, Pierre ^{[1
]}

Wahl, Daniel ^{[1
]}

Mahl, Andreas ^{[1
]}

End, Peter ^{[1
]}

Staedtler, Frank ^{[1
]}

Legay, Francois ^{[1
]}

Carl, Kevin ^{[1
]}

Laurie, David ^{[1
]}

Chibout, Salah-Dine ^{[1
]}

Vonderscher, Jacky ^{[1
]}

Maurer, Gerard ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, Basel, Switzerland

来源：

NATURE BIOTECHNOLOGY | 2010年 / 28卷 / 05期

关键词：

GLOMERULAR-FILTRATION-RATE; ALANINE AMINOPEPTIDASE; GENE-EXPRESSION; RAT; BIOMARKERS; NEPHROTOXICITY; GENTAMICIN; DYSFUNCTION; IMPAIRMENT; EXCRETION;

D O I：

10.1038/nbt.1622

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：

Earlier and more reliable detection of drug-induced kidney injury would improve clinical care and help to streamline drug-development. As the current standards to monitor renal function, such as blood urea nitrogen (BUN) or serum creatinine (SCr), are late indicators of kidney injury, we conducted ten nonclinical studies to rigorously assess the potential of four previously described nephrotoxicity markers to detect drug-induced kidney and liver injury. Whereas urinary clusterin outperformed BUN and SCr for detecting proximal tubular injury, urinary total protein, cystatin C and beta 2-microglobulin showed a better diagnostic performance than BUN and SCr for detecting glomerular injury. Gene and protein expression analysis, in-situ hybridization and immunohistochemistry provide mechanistic evidence to support the use of these four markers for detecting kidney injury to guide regulatory decision making in drug development. The recognition of the qualification of these biomarkers by the EMEA and FDA will significantly enhance renal safety monitoring.

引用

页码：463 / U114

页数：10

共 43 条

[1] EFFECTS OF GENTAMICIN ON THE RENAL UPTAKE OF ENDOGENOUS AND EXOGENOUS PROTEINS IN CONSCIOUS RATS [J].