Chapter 20: Renal Toxicity
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Published:15 Nov 2011
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Special Collection: 2011 ebook collection , 2011 ebook collection , 2011-2015 industrial and pharmaceutical chemistry subject collectionSeries: Drug Discovery Series
K. Nasir, M. Khan, G. C. Hard, and Z. A. Radi, in New Horizons in Predictive Toxicology: Current Status and Application, ed. A. G. E. Wilson, The Royal Society of Chemistry, 2011, ch. 20, pp. 499-541.
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The past 10 years have seen remarkable advances in application of new molecular and investigative techniques in detecting and understanding chemically induced renal injury in pre-clinical safety evaluation studies, as well as for renal disease states in humans. These efforts should eventually culminate in a much safer level of pharmaceutical drug use. The development of sophisticated technology has played an important role in the discovery of novel biomarkers of renal injury. Antibody-based proteomics in particular will continue to be an essential contribution to unraveling the complexity of the kidney's response to chemically induced toxicity. Furthermore, these high-throughput screening methods of “-omics” profiling introduce the prospect of developing personalized medical treatment in the future.
This chapter provides an overview of the utilization of basic principles of renal anatomy, physiology, and biomarkers to aid in predicting nephrotoxic responses of chemicals and novel experimental medicines. Additionally, a concise review is provided on the in vivo and in vitro models of nephrotoxicity and application of emerging technologies including toxicogenomics, proteomics, and metabonomics, and novel renal biomarkers to predict localization of renal damage. Rodents are used in majority of discussions as these are the most frequently used animal species in nephrotoxicity assessments.