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.