Nephrotoxicity biomarkers

Genomic biomarkers have been reported for a variety of tissues such as kidney.11 Among those identified markers, many can be deemed as mechanistic biomarkers as they are not merely correlated to, but biologically linked to, the underlying toxicity. For example, Kim-1, one of the nephrotoxicity biomarkers submitted to FDA by PSTC is an endogenous ciliary flow-sensing protein that responds to kidney malfunction.12... 

Astashkina Al, Mann BK, Prestwich GD, Grainger DW. 2012b. Comparing predictive drug nephrotoxicity biomarkers in kidney 3-D primary organoid culture and immortalized cell lines. Biomaterials 33(18) 4712-4721. 

EMA, 2009. Final conclusions on the pilot Joint EMEA/FDA VXDS experience on Qualification of Nephrotoxicity biomarkers. http //www.c-path.org/p(U7EMAreport.pdf (accessed October 22, 2015). 

EMA. Final conclusions on the pilot joint EMEA/FDA VXDS experience on qualification of nephrotoxicity biomarkers. 2008. Available at http //www.ema.europa.eu/docs/en GB/document library/Regulatory and procedural guideline/2009/10/ WC500004205.pdf Accessed May 20, 2015. 

Meistermann H, Norris J, Aerni H, et al. Biomarker discovery by imaging mass spectrometry transthyretin is a biomarker for gentamicin-induced nephrotoxicity in rat. Mol. Cell. Proteomics 2006 5 1876-1886. 

Finn WF, Porter GA (1998) Urinary biomarkers and nephrotoxicity. In DeBroe ME, Porter GA, Bennett WM, Verpooten GA (eds) Clinical Nephrotoxins. Kluwer Academic Publishers, Dordrecht, Netherlands, pp 61-99 Finney H, Newman DJ, Gruber W, Merle P, Price CP (1997) Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelemeter systems (BNA, BN II). Clin Chem 43 1016-1022... 

Price RG, Taylor SA, Chivers I et al. (1996) Development and validation of new screening tests for nephrotoxic effects. Hum Exper Toxicol 15 S10-S19 Price RG, Berndt WO, Finn WF et al. (1997) Urinary biomarkers to detect significant effects of environmental and occupational exposure to nephrotoxins, III. Minimal battery of tests to assess subclinical nephrotoxicity for epidemiological studies based on current knowledge 19 535-552 Price RG (2000) Urinalysis to exclude and monitor nephrotoxicity. Clin Chim Acta 297 173-182 Price RG (2002) Early markers of nephrotoxicity. Comp Clin Pathol 11 2-7... 

Using the toxicogenomic techniques described, some significant data have been obtained but to determine the functional significance of these data, additional studies need to be done. Use of these new technologies and their specificity and sensitivity to assess nephrotoxicity remains controversial, but in the future they may allow the identification of useful biomarkers that would be predictive of future responses to toxicant insults and the region of the kidney affected. Identification of specific biomarkers associated with the future development of loss of kidney function, fibrosis, or recovery would be useful in the rapid evaluation of potentially nephrotoxic agents. 

Metabolomics has made remarkable inroads into the environmental research community. Here, a major emphasis is to understand the impact that environmental stress, such as pollution and climate change, has on wildlife. Indeed, many government organizations monitor the prevalence of pollutants in certain species of wildlife as indicators of the exposure risk within the environment. Studies of Japanese medaka have been conducted to investigate the effects of trichloroethylene, a common environmental pollutant, and the pesticide dinoseb, on the development of fish embryos (44, 45). Similarly, cadmium toxicity has been examined in the bank vole and rat and has revealed changes in lipid metabolism that preceded classical nephrotoxicity (46, 47). Another study investigated the effects of environmental toxins on earthworms (48). In particular, the analysis of earthworm tissue extracts by NMR spectroscopy identified maltose as a potential biomarker for ecotoxicity within a metal-contaminated site. 

When considering the application of urinary enzymes to monitor subtle renal dysfunction and/ or to clarify mechanisms of nephrotoxicity, only a limited number of enzymes have been generally accepted as valuable urinary biomarkers. These include lactic dehydrogenase, N-acetyl-P-l>glucosarriitiidase (NAG), alanine aminopeptidase (AAP), intestinal alkaline phosphatase, glutathione-S-transferase, gamma-glutamyl transferase and fructose-l,6,-biphosphatase. 

Roels HA, Hoet P, Lison D. Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity. Ren Fail. 1999 May-Jul 21(3-4) 251-62. 

Mishra J, Mori K, Ma Q, et al. Neutrophil gelatinase-associated lipocalin a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 2004 24 307-315. 

Ishii A, Sakai Y, Nakamura A. Molecular pathological evaluation of clusterin in a rat model of unilateral ureteral obstruction as a possible biomarker of nephrotoxicity. Toxicol Pathol. 2007 35 376-82. 

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