Current approaches for sensitive detection of drug-induced acute kidney injury

Yutaka Tonomura, Mitsunobu Matsubara, Takeki Uehara

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The kidney is particularly vulnerable to various drugs. Early screening of druginducedacute kidney injury (AKI) is therefore critical for its clinical management,leading to a better outcome of clinical treatment. For the pharmaceutical industry, druginducedAKI is a major concern in the early stage of preclinical safety evaluations. Onemajor limitation in early detection of AKI has been the low detection power of traditionalbiomarkers, such as creatinine and blood urea nitrogen. Recent advances in basic andclinical research have provided several valuable biomarkers for early detection of AKIfor the preclinical safety evaluation of drugs, clinical trials, and early therapeuticintervention. Serum cystatin c (CysC) has been identified as an attractive alternativebiomarker for estimation of the glomerular filtration rate. Additionally, severalbiomarkers, such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associatedlipocalin, interleukin-18 and liver type fatty acid binding protein, have been discoveredand their usefulness has been evaluated in cross-sectional studies. Recently, thePredictive Safety Testing Consortium's Nephrotoxicity Working Group, a collaborationbetween biotech and pharmaceutical industries, the US Food and Drug Administration(FDA), the European Medicines Agency (EMEA) and academia, published a reportconcerning the qualification of seven urinary nephrotoxic biomarkers, including totalprotein, albumin, KIM-1, clusterin (CLU), β2-microglobulin, CysC, and trefoil factor 3,for particular uses in regulatory decision-making. Furthermore, the International LifeSciences Institute Health and Environmental Sciences Institute reported an extensive datapackage on the four urinary nephrotoxic biomarkers glutathione S-transferase α (GSTα), GSTμ, renal papillary antigen-1 and CLU to the FDA and the EMEA. This chapterdescribes the usefulness of these biomarkers with respect to clinical and preclinical usageand the possible mechanisms that underlie their alterations in serum and/or urine. Finally,we discuss the future view of AKI biomarkers.

Original languageEnglish
Title of host publicationCystatins
Subtitle of host publicationProtease Inhibitors, Biomarkers and Immunomodulators
PublisherNova Science Publishers, Inc.
Pages143-164
Number of pages22
ISBN (Print)9781612093437
Publication statusPublished - 2011 Apr 1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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