Relationship of kidney function to immunopathology in chronic serum sickness of rats

This study sought to clarify the relationship between kidney function and immunopathology in chronic serum sickness (CSS) of rats. CSS was induced by chronic intravenous immunization with bovine serum albumin. Whole kidney function was studied during the course of CSS by assays of serum and urine. Single nephron function was evaluated by micropuncture techniques. Three categories (mild, moderate, severe) of kidney disease were identified from the analysis of kidney function in rats with CSS. Those categories represented distinct stages in the natural history of CSS nephritis. The three stages identified by measurements of function corresponded to distinct categories of kidney immunopathology. In rats with milk CSS, immune deposits were limited to the mesangium; histopathology was slight or absent. The only detectable change in protein handling was a small elevation of albumin concentration in tubule fluid. Abnormal proteinuria was a feature of moderate CSS; whole kidney glomerular filtration was not decreased despite evidence of significant immunopathology of glomeruli. Compromise of whole kidney function including decreased sodium excretion was only detected in the severe stage of CSS in association with diffuse proliferative glomerulonephritis. The transitions from mild to moderate and moderate to severe CSS were not gradual but occurred as discrete, sudden events.