Sudden onset of proteinuria in chronic serum sickness in rats.

1. Daily intravenous administration of bovine serum albumin (BSA) to rats produces chronic serum sickness glomerulonephritis, an immune-complex-mediated renal disease that is eventually always fatal. We have performed a detailed study of the onset of proteinuria in chronic serum sickness in order to assess the long-term consequences of discontinuing daily BSA injections precisely at that very early and well-defined stage of disease. 2. Urine and plasma samples from rats receiving daily BSA injections were collected and analysed daily before the onset of proteinuria, at which time the rats were divided into three groups. Group 1 continued to receive daily BSA injections, in group 2 injections were stopped on the first, and in group 3 on the third, day of proteinuria. Proteinuria began suddenly and was not preceded either by microalbuminuria or abnormalities of plasma composition. The sudden expression of proteinuria was accompanied by an equally rapid development of hypoalbuminaemia and hypercholesterolaemia. Development of the characteristic glomerular histopathology of serum sickness coincided with, but did not precede, the onset of proteinuria. Despite the discontinuation of antigen injections at the onset of proteinuria, basement membrane thickening was evident 8 weeks later; proteinuria persisted and hypercholesterolaemia increased. 3. In this model of immune complex glomerulonephritis, changes in kidney function and immunopathology were abrupt and closely linked, precluding the use of those criteria to predict when proteinuria would begin. Furthermore, extremely brief periods of active immunological injury to the peripheral capillary wall were sufficient to produce persistent abnormalities of glomerular structure and function.