title: The relationship between chemical-induced kidney weight increases and kidney histopathology in rats.
abstract: The kidney is a major site of chemical excretion, which results in its propensity to exhibit chemically-induced toxicological effects at a higher rate than most other organs. Although the kidneys are often weighed in animal toxicity studies, the manner in which these kidney weight measurements are interpreted and the value of this information in predicting renal damage remains controversial. In this study we sought to determine whether a relationship exists between chemically-induced kidney weight changes and renal histopathological alterations. We also examined the relative utility of absolute and relative (kidney-to-body weight ratio) kidney weight in the prediction of renal toxicity. For this, data extracted from oral chemical exposure studies in rats performed by the National Toxicology Program were qualitatively and quantitatively evaluated. Our analysis showed a statistically significant correlation between absolute, but not relative, kidney weight and renal histopathology in chemically-treated rats. This positive correlation between absolute kidney weight and histopathology was observed even with compounds that statistically decreased terminal body weight. Also, changes in absolute kidney weight, which occurred at subchronic exposures, were able to predict the presence or absence of kidney histopathology at both subchronic and chronic exposures. Furthermore, most increases in absolute kidney weight reaching statistical significance (irrespective of the magnitude of change) were found to be relevant for the prediction of histopathological changes. Hence, our findings demonstrate that the evaluation of absolute kidney weight is a useful method for identifying potential renal toxicants.
authors.affiliation: Oak Ridge Institute for Science and Education, Oak Ridge, 37831, TN, USA.|National Center for Environmental Assessment, Office of Research Development, U.S. Environmental Protection Agency, Cincinnati, 45268, OH, USA.
authors.forename: Evisabel A
authors.initials: EA
authors.lastname: Craig
authors.affiliation: Oak Ridge Institute for Science and Education, Oak Ridge, 37831, TN, USA.|National Center for Environmental Assessment, Office of Research Development, U.S. Environmental Protection Agency, Cincinnati, 45268, OH, USA.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Yan
authors.affiliation: National Center for Environmental Assessment, Office of Research Development, U.S. Environmental Protection Agency, Cincinnati, 45268, OH, USA.
authors.forename: Q Jay
authors.initials: QJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects*; D051381:Rats; D018675:Toxicity Tests
keywords: absolute kidney weight; kidney histopathology; relative kidney weight; renal toxicity; risk assessment