Urinary Clusterin, Cystatin C, Beta2-microglobulin and Total Protein As Markers to Detect Drug-induced Kidney Injury

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2010 May 12

PMID 20458316

Citations 105

Authors

Frank Dieterle

Elias Perentes

Andre Cordier

Daniel R Roth

Pablo Verdes

Olivier Grenet

Serafino Pantano

Pierre Moulin

Daniel Wahl

Andreas Mahl

Peter End

Frank Staedtler

Francois Legay

Kevin Carl

David Laurie

Salah-Dine Chibout

Jacky Vonderscher

Gerard Maurer

Affiliations

Soon will be listed here.

Abstract

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 beta2-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.

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