A transition from proliferative to membranous glomerulonephritis in chronic serum sickness

Chronic serum sickness glomerulonephritis was induced in rats by daily i.v. administration of bovine serum albumin (BSA). Previous studies have shown that the disease progresses through three discrete stages: mild, moderate and severe. The diffuse, proliferative necrotizing glomerulonephritis of severe chronic serum sickness, which is accompanied by a decreased glomerular filtration rate and increased glomerular permeability to macromolecules, has an inevitable fatal outcome. In the experiments reported here, BSA injections were discontinued at the transition from moderate to severe glomerulonephritis, a point which was identified by decreased sodium excretion. Retrospectively, rats could be divided into two categories. Some, called non-survivors, continued to exhibit sodium retention. Those animals progressed rapidly to end-stage renal disease and died within two weeks of the cessation of antigen injections. Others, called survivors, returned to sodium balance and remained alive for many months. The development of progressive membranous glomerulonephritis, with prominent spike formation and disappearance of glomerular hypercellularity, was noted in all survivors. That change in histopathology occurred in the absence of both circulating BSA and precipitating antibodies to BSA. The transition of proliferative to membranous glomerulonephritis was accompanied by partial recovery of glomerular function, although proteinuria persisted. Maintenance of severe proteinuria did not appear to depend on an active immunological process.