Experimental Glomerulonephritis

Abstract

A direct correlation between the amount of kidney-fixing antibody and the degree of associated renal injury was demonstrated for rabbit and duck nephrotoxic antibodies. No evidence for a qualitative difference among nephrotoxic antibodies of a given type was obtained. It appeared that duck nephrotoxic antibody was directed against a wider spectrum of rat renal antigens than was rabbit nephrotoxic antibody. In order to produce immediate proteinuria an amount of rabbit or duck gamma-2 kidney-fixing antibody capable of occupying approximately 45 per cent or more of the capillary filtration surface was needed. For immediate proteinuria an amount of rabbit gamma-2 kidney-fixing antibody capable of reacting with more than one-half of the available antigenic sites was needed. Less than twice that amount of rabbit antibody completely saturated available antigenic sites in the kidney. Virtually all nephrotoxic antibodies in hyperimmune rabbit nephrotoxic sera were of the gamma-2 variety while nephrotoxic antibodies in comparable duck nephrotoxic sera were found in gamma-2 (with 5.8 and 7.4S sedimentation coefficients) and gamma-1M fractions. Gamma-1M duck nephrotoxic antibody was 60 times more potent a nephritogen than gamma-2 duck nephrotoxic antibody on a molecular basis. Mercaptoethanol abolished the nephrotoxicity of gamma-1M duck antibody and reduced that of gamma-2 duck antibodies but had no effect on rabbit gamma-2. In no case did mercaptoethanol treatment have an effect on the kidney-fixing properties of the antibodies involved. After injection of nephrotoxic antibodies there appeared to be a prompt fixation of a majority of the antibody to tissue antigens primarily in the kidney. However, a small amount of potentially kidney-fixing antibody remained in the circulation for a considerable period apparently reflecting a dissociation of less avid antibodies with an equilibrium between fixed and free antibody. The role of this more easily dissociable antibody in the progression of nephrotoxic nephritis is not certain but it is possible that it could play a role in the early progression of the disease.

Experimental Allergic Glomerulonephritis Induced in the Rabbit With Heterologous Renal Antigens

“…From quantitative studies in nephrotoxic serum nephritis, it is known that the development of immediate or late renal injury depends upon the amounts of glomerular antigenic sites reacting with antibody (28,34). If the number of antigenic sites was large and there was sufficient antibody to fix to them, nephritis would develop within a matter of hours (28). If, on the other hand, the number of antigenic sites was small, nephritis, if it developed at all, did so only after a prolonged period of antigenantibody interaction (34).…”

“…The amounts of antibody in the various rabbit antisera were judged by the amounts of immediate proteinuria they would induce when injected into rats (28). The rabbits were bled 16 days after the last immunization.…”

Experimental Glomerulonephritis

“…Only slight quantitative differences were noted among these NTGGs and no attempt will be made to differentiate them. The amount of kidney-fixing antibody (KFAb) for each preparation of NTGG was determined as previously described (6) and averaged 300/zg of KFAb per 10 mg of rabbit NTGG. Three levels of KFAb were employed: 380/zg per rat which induces an immediate and continuing proteinuria of 180 to 250 nag per 24 hours; 180 #g per rat which causes an immediate and continuing proteinuria of 20 to 60 mg per 24 hours; and 2 to 45 #g per rat which causes no detectable renal abnormalities.…”

“…Rats which 14 days previously had received 35 #g of KFAb were injected with 1 mg of I13Llabeled rat GG containing 93 #g of anti-rabbit GG antibody. The techniques of obtaining and iodinating rat GG have been described previously (5,6). After injection of the labeled protein, 2 to 4 rats were sacrificed at different time intervals and the amount of radioactivity was determined in the kidney after peffusion in ~ivo with NaC1, 0.15 M. The whole kidneys were counted in a sodium iodide crystal scintillation counter; all counts were corrected for background and decay of I18x; the results of each group of rats were averaged and expressed as percentage of injected material fixed to the kidney.…”

“…First, the immediate immunologic events which lead to acute injury necessitate the involvement of half or more of the filtration surface of the glomerular capillaries by antibody (6). Under these circumstances the glomerular capillaries and/or nephrons appear to be quite resistant to the effects of a sizeable, acute immunologic insult.…”