Assessment of Nephrotoxicity

Evaluation of the effects of a toxicant on renal function can be accomplished by several methods. The method used depends on the complexity of the question to be answered. For example, unanesthetized or anesthetized animals may be used to determine if a chemical has an effect on kidney function. Investigations also may be conducted in vitro to examine specific biochemical or functional lesions. Finally, histopathologic techniques can provide a great deal of information about structural integrity. 

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WHO/IPCS. 1991. Principles and methods for the assessment of nephrotoxicity associated with exposru-e to chemicals. Environmental Health Criteria 119. Geneva WHO. http /www.inchem.org/documents/ ehc/ehc/ehcl 19.htm... 

The focus of this chapter is threefold (1) to review components of renal physiology contributing to susceptibility to chemically induced nephrotoxicity, (2) to examine current methodologies for assessment of nephrotoxicity, and (3) to provide examples of a few specific nephrotoxicants, emphasizing mechanisms thought to contribute to the unique or selective susceptibility of specific nephron segments to these toxicants. 

Eikmans, M., Baelde, H. J., de Heer, E., and Bruijn, J. A. RNA expression profiling as prognostic tool in renal patients toward nephrogenomics. Kidney Int. 62,1125-1135, 2002. Gibbs, A. Comparison of the specificity and sensitivity of traditional methods for assessment of nephrotoxicity in the rat with metabonomic and proteomic methodologies. J. Appl. Toxicol. 25, 277-295, 2005. 

Sandler DP. Epidemiology in the assessment of nephrotoxicity, in Nephrotoxicily in the experimental and clinical situation. Bach... 

Table 1. Endpoints for assessment of nephrotoxicity on renai cell culture systems. ...

Aguado JM, Eumbreras C, Gonzalez-Vidal D. Assessment of nephrotoxicity in patients receiving amphotericin B lipid complex a pharmacosurveillance study in Spain. Clin Microbiol Infect 2004 10 785-90. 

Cesaro S, Zignol M, Burlina AB, et al. Assessment of nephrotoxicity of high-cumulative dose of liposomal amphotericin B in a pediatric patient who underwent allogenic bone marrow transplantation. Pediatric Transplantation 2006 10 255-8. 

Salama SE, Rotstein C. Prospective assessment of nephrotoxicity with concomitant aminoglycoside and vancomycin therapy. Can J Hosp Pharm 1993 46 53-59. 

Several urinary enzymes are useful in the assessment of nephrotoxicity, and these are discussed separately in Chapter 4. Although there is some application of cholinesterases in studying hepatotoxicity, these enzymes are important markers in pesticide-induced toxicities and are discussed in Chapter 11. Creatine kinase (CK) remains a useful marker for myotoxicity, but it is rapidly losing its place to troponins in the detection of cardiotoxicity (see Chapter 7). Amylase and lipase remain the enzyme markers of pancreatic toxicity. 

Assessment of nephrotoxicity. In Animal clinical chemistry. A primer for toxicologists, ed. G. O. Evans, pp. 87-98. London Taylor Francis Ltd. 

PREDICTIVE IN VITRO MODELS FOR ASSESSMENT OF NEPHROTOXICITY AND DRUG-DRUG INTERACTIONS IN VITRO... 

Stonard, M.D., Assessment of Nephrotoxicity, in Animal Clinical Chemistry, G.O. Evans, Editor. 1996, Taylor Francis London, p. 87-9. 

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