Experimental nephropathy induced by human polyclonal light chains

We describe the nephrotoxic effects of a preparation of light chains (LC) obtained by reduction and alkylation of human IgG. The acute renal lesions in rats are dependent upon the dose and route of LC administration. The kidney alterations were not observed in animals treated with comparable amounts of human albumin or the F(ab')2 fragment of human IgG. Intravenous bolus injection of 120 mg LC into 80-100 g hydropenic rats induced extensive cast formation in distal and collecting renal tubules, which were similar to the human "myeloma kidney". In contrast, the slow infusion of the same amount of LC over 1 h produced degenerative changes in the proximal tubular cells without extensive cast formation. The morphological alterations of the kidney were investigated by classical histological methods, by immunofluorescence and in thin sections stained with toluidine blue. Urinary excretion and kidney content of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were increased only in the group of animals infused with LC. These findings may be relevant to the pathogenesis of human nephropathy occurring in multiple myeloma and in some autoimmune diseases.