Immunopathology of the Urinary System

The pathogenesis of many immune-mediated diseases of the urinary tract has been well elucidated in humans and in their respective animal models. While laboratory animals develop spontaneous immune-mediated renal disease, far less is known about their etiology or pathogenesis. By examining the five types of hypersensitivity reactions that lead to immune-mediated glomerular disease in humans, and understanding the molecular pathogenesis of lesion development, toxicologic pathologists can interpret test article-related lesions in the urinary tract, and help distinguish these lesions from spontaneous disease. Resident macrophages and dendritic cells of the kidney maintain continual tolerance, and any disruption of this homeostasis will result in glomerular and/or tubulo-interstitial inflammation which often self-perpetuates leading to end stage renal disease. Although immune dysfunction leads to renal disease, the reverse is true as well. Uremia leads to immunodysfunction, hypercytokinemia, and multi-organ damage especially to the cardiovascular system.