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Biomarkers for Drug-Induced Renal Damage and Nephrotoxicity—An Overview for Applied Toxicology

  • Review Article
  • Theme: Biomarkers of Drug-Induced Organ Toxicity
  • Published:
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Abstract

The detection of acute kidney injury (AKI) and the monitoring of chronic kidney disease (CKD) is becoming more important in industrialized countries. Because of the direct relation of kidney damage to the increasing age of the population, as well as the connection to other diseases like diabetes mellitus and congestive heart failure, renal diseases/failure has increased in the last decades. In addition, drug-induced kidney injury, especially of patients in intensive care units, is very often a cause of AKI. The need for diagnostic tools to identify drug-induced nephrotoxicity has been emphasized by the ICH-regulated agencies. This has lead to multiple national and international projects focusing on the identification of novel biomarkers to enhance drug development. Several parameters related to AKI or CKD are known and have been used for several decades. Most of these markers deliver information only when renal damage is well established, as is the case for serum creatinine. The field of molecular toxicology has spawned new options of the detection of nephrotoxicity. These new developments lead to the identification of urinary protein biomarkers, including Kim-1, clusterin, osteopontin or RPA-1, and other transcriptional biomarkers which enable the earlier detection of AKI and deliver further information about the area of nephron damage or the underlying mechanism. These biomarkers were mainly identified and qualified in rat but also for humans, several biomarkers have been described and now have to be validated. This review will give an overview of traditional and novel tools for the detection of renal damage.

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Authors and Affiliations

  1. Toxicology, Merck Serono, Frankfurter Strasse 250, 64293, Darmstadt, Germany

    Tobias Christian Fuchs & Philip Hewitt

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  1. Tobias Christian Fuchs
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  2. Philip Hewitt
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Correspondence to Philip Hewitt.

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Guest Editors: Brian Booth and Murali Ramanathan

ELECTRONIC SUPPLEMENTARY MATERIALS

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Supplementary Fig. 1

Overview of RIFLE and AKIN processes for assessing DIKI/AKI. Patients who receive renal replacement therapy (RRT) are classified as stage 3 in the AKIN schema (Cr serum creatinine, GFR glomerular filtration rate, AKI acute kidney injury; JPEG 25 kb)

High-resolution image (TIFF 4,752 kb)

Supplementary Fig. 2

The overlap of human, mouse, and rat miRNAs identified in renal tissue shows the conservation of miRNA over different species. The total number of miRNAs determined per species is shown under the name of species. Out of these, a number of 73 miRNAs were detectable in all three species. Adapted from (44) (JPEG 9 kb)

High resolution image (TIFF 541 kb)

Supplementary Table I

The five kidney damage stages discerned by the GFR (DOC 29 kb)

Supplementary Table II

An overview of international projects focused on the identification of biomarkers for the detection of nephrotoxicity using novel technologies like toxicogenomic and proteomics (DOC 32 kb)

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Fuchs, T.C., Hewitt, P. Biomarkers for Drug-Induced Renal Damage and Nephrotoxicity—An Overview for Applied Toxicology. AAPS J 13, 615–631 (2011). https://doi.org/10.1208/s12248-011-9301-x

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  • DOI: https://doi.org/10.1208/s12248-011-9301-x

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