14.18 - α2u-Globulin Nephropathy

Abstract

This article describes the histopathology, biochemical mechanisms, and human relevance of the renal syndrome referred to as α2u-globulin nephropathy, a renal syndrome that occurs only in male rats. A variety of environmental chemicals, naturally occurring compounds, and pharmaceuticals have been shown to elicit this syndrome that is observed acutely as the accumulation of protein droplets in the renal proximal tubule. With chronic exposure however, these compounds also cause renal cancer in male rats. In-depth mechanistic studies have demonstrated that the male rat-specific protein, α2u-globulin, is required for the toxic and carcinogenic response. The mechanistic studies detailed in the article have also provided the foundation for evaluating the relevance of these findings for human risk assessment. The mechanism of renal toxicity associated with α2u-globulin nephropathy provided an important precedent in toxicology and cancer risk assessment for establishing how mode of action data in laboratory animals can be applied to human risk assessment.