Comparison of the specificity and sensitivity of traditional methods for assessment of nephrotoxicity in the rat with metabonomic and proteomic methodologies

There is currently a great deal of scientific interest and debate concerning the possible advantages that proteomic and metabonomic technologies might have over traditional biomarkers of toxicity (blood and urine chemistry, histopathology). Numerous papers have been published that make impressive claims concerning potential applications for these novel technologies, however there appears to be little hard evidence in the literature of their advantages over the traditional techniques for assessing toxicity. The aim of this review was to evaluate the relative sensitivity and specificity of proteomic and metabonomic techniques, compared with traditional techniques, for assessing xenobiotic-induced nephrotoxicity. A review of studies was performed where both one of the novel methods as well as traditional techniques were used for assessment of xenobiotic-induced nephrotoxicity. There was no consistent evidence from the literature that the novel methodologies were any more sensitive than the traditional methods for assessing nephrotoxicity. This could be due to the relatively small number of studies available for review (n = 13), the fact that generally these studies were not aimed at determining relative sensitivity or specificity and may not be the case with other target organs, such as the liver. However, it was clear that the novel methodologies were able to discriminate between the effects caused by different toxicants. There was evidence both that this discrimination was on the basis of different mechanisms of toxicity and on the basis of different locations of nephrotoxic lesion. A great deal of validation work is necessary before these techniques could gain full acceptance by regulatory authorities, and it is unclear whether their use in anything other than non-regulatory, mechanistic studies is likely to become widespread.