Biomarkers of Exposure to Toxic Substances. Volume 5: Biomarker Pre- validation Studies Prevalidation of Urine and Serum Biomarkers Indicative of Subclinical Kidney Damage in a Nephrotoxin Model

摘要

Once biomarkers have been identified using Omics technologies, assays must be developed and the markers pre-validated in both the test model samples and in other relevant kidney injury models. To initiate work to examine biomarkers to subclinical kidney injury, two separate efforts were conducted. First, extensive literature searches were conducted to compile a list of potential kidney injury markers identified in other disease or injury models, either human or animal. Secondly, unique markers identified through RHPB's Omics efforts were examined. In both cases, urinary protein markers were analyzed for sensitivity and selectivity for injury levels, regional damage, temporal response and dose response following nephrotoxin exposure. Two experimental nephrotoxins were interrogated, D-serine and puromycin, each previously demonstrated to degrade a specific kidney segment (proximal tubule and glomerulus, respectively). In this study a total of seventeen protein biomarkers were evaluated, with ten journal-based markers pre-validated and two unique RHPB markers partially pre-validated. Two other RHPB markers were examined and pre-validation was partially completed. The current panel set of 11 biomarkers is indicative of very low level subclinical kidney damage/dysfunction with a response range in the urine between the earliest time point of 12 hours to a maximum of 96 hours post-toxin exposure.