NEPHROTOXICITY OF HUMAN BENCE-JONES PROTEIN IN RATS - PROTEINURIA ANDENZYMURIA PROFILE

The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wista r rats (N = 7; 2 months old). A state of immunological tolerance was d emonstrated by the absence of a B-cell response (plaque-forming cells and hemagglutination titers) and by the absence of detectable antigen or antibody deposition in glomeruli, as indicated by light and electro n microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 v s 32.8 +/- 1.3 mg%). There was an increase in proteinuria (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significa nt increase of lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/- 18.8 mU/mg in creatinine). Lysosomal accumula tion of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly s howed proximal tubular dysfunction induced by chronic Bence Jones prot ein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance.