Utility of Kidney Biomarkers in Preclinical Toxicology Studies (S01-3)

Given the low sensitivity of traditional renal biomarkers— blood urea nitrogen (BUN) and serum creatinine (sCr)—, DIKI in preclinical toxicology studies is usually identified through histological examination, which may or may not be accompanied by corresponding changes in traditional renal biomarkers. However, histopathology cannot be used to monitor for DIKI during clinical studies. To this end, over the last decade, several novel urinary biomarkers have been identified for the early detection of renal injury in preclinical species. Most of these urinary biomarkers (total protein [TP], albumin [ALB], kidney injury molecule-1 [KIM-1], osteopontin [OPN], neutrophil gelatinase-associated lipocalin [NGAL], N-acetyl-b-D-glucosaminidase [NAG], cystatin C [CysC], clusterin [CLU], and 2-microglobulin [B2M]) have been qualified or received a Letter of Support from regulatory agencies for use in rat, and 6 of these biomarkers (CLU, CysC, KIM-1, NAG, NGAL, and OPN) have been qualified for use via a composite measure in human clinical studies. Using published data, this presentation will highlight the utility of these novel biomarkers in commonly used preclinical animal species for toxicology studies including rats, mice, beagle dogs and cynomolgus monkeys. The value of these biomarkers in human and rat proximal renal tubular 2D in vitro model and 3D microphysiological systems will also be presented.