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.

Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene

“…2017c). However, change in absolute kidney weight, but not kidney-to-BW ratio, is an accepted predictor of kidney histopathology in subchronic and chronic studies (Craig et al. 2015).…”

Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice

“…Of particular note was the finding that the AUC 0-12h of TCVC, which may be metabolically activated to electrophilic, cytotoxic, genotoxic, and/or mutagenic intermediates, was approximately 30%-40% lower in the kidneys of mice with NAFLD compared with LFD-fed mice. Biochemical and Histopathological Evaluation of Kidney Injury Absolute kidney weight, but not kidney-to-bodyweight ratio, has been shown to correlate strongly with sub-chronic and chronic renal injury in rats (Craig et al, 2015). Absolute kidney weight was unaffected by diet or PERC exposure (Table 1); however, kidney-to-body weight ratio was decreased in HFD-fed mice compared with LFD-fed control, and was significantly increased by PERC exposure in all three diet groups.…”

The Histomorphometry of Liver and Kidney of Hyperglycemic Albino Rats after Treatment with Tithonia diversifolia Leaf Extract

“…The results of glomerular diameter measurements were in the normal range and necrosis has not occurred, so the kidney weight in albino rats is also normal. Craig et al (2015) reported kidney weight correlation with kidney histopathology. According to Rasch & Dørup (1997), diabetic rats can increase kidney weight by 53 -93%.…”