title: Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria profile.
abstract: The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2 months old). A state of immunological tolerance was demonstrated 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 electron microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 vs 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 significant 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 accumulation of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly showed proximal tubular dysfunction induced by chronic Bence Jones protein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance.
authors.affiliation: Laboratório de Fisiopatologia Renal, Faculdade de Medicina, Universidade de São Paulo, Brasil.
authors.forename: M J
authors.initials: MJ
authors.lastname: Prado
authors.forename: A L
authors.initials: AL
authors.lastname: Nicastri
authors.forename: P
authors.initials: P
authors.lastname: Leo
authors.forename: E
authors.initials: E
authors.lastname: Uchino
authors.forename: A
authors.initials: A
authors.lastname: Sesso
authors.forename: M
authors.initials: M
authors.lastname: Marcondes
authors.forename: E B
authors.initials: EB
authors.lastname: Prado
mesh_terms: D000818:Animals; D001536:Bence Jones Protein / Q000009:adverse effects*; D004798:Enzymes / Q000652:urine*; D007147:Immunoglobulin Light Chains / Q000009:adverse effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000648:ultrastructure; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D009101:Multiple Myeloma / Q000276:immunology; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004798:Enzymes; D007147:Immunoglobulin Light Chains; D001536:Bence Jones Protein