Glomerulonephritis in Animal Models and Human Medicine: Discovery, Pathogenesis, and Diagnostics

Abstract

Glomerulonephritis (GN) is inflammation of glomeruli. The four major categories that cause human GN are mediated by immunoglobulin or complement or both, and they include (1) immune complex–mediated GN, (2) anti-glomerular basement membrane–mediated GN, (3) antineutrophil cytoplasmic autoantibody–mediated GN, and (4) complement factor 3 glomerulopathy mediated by complement dysregulation. Initiating processes include infection, autoimmunity, exogenous antigens, and neoplasia. Often there are predisposing and modulating genetic, epigenetic, and/or environmental factors. Animal models facilitated the recognition and elucidation of the pathogeneses of all four categories of GN, and they continue to be used in preclinical studies to identify and validate therapies for all four types of GN. Advanced diagnostic modalities (e.g., transmission electron microscopy and immunofluorescence) are helpful and sometimes required for the correct categorization of GN in humans and animals. This review provides historical background on the discovery of the different GN pathogeneses, describes some of the animal models used to discover and understand each GN pathogenic category, reviews the diagnostic classification of each category of GN, and compares human GN to spontaneous forms of nonhuman GN.