Acute cryoglobulinemic renal failure after intravenous infusion of gamma globulin

A 39-year-old woman had mixed IgM/IgG cryoglobulinemia, but was later found to have a lymphoma that produced an IgM kappa paraprotein with rheumatoid factor activity. With intermittent chlorambucil and prednisone therapy, the lymphoma was controlled for five years and she had no evidence of cryoglobulinemia. Because of the presence of intractable pulmonary infection and hypogammaglobulinemia G, she was given an intravenous infusion of gamma globulin. Within 72 hours, renal failure and a sustained decrease in serum concentrations of IgM and IgG began concurrently. A kidney biopsy specimen obtained five days after the infusion showed hyaline "thrombi" in numerous glomerular capillaries and glomerular necrosis, consistent with acute, severe mixed cryoglobulinemic nephropathy. Immunostaining showed strong positivity for IgM, IgG, and light chains in glomerular capillary lumina and subendothelial sites; immunostaining with a monoclonal antiidiotypic antibody specific for the patient's paraprotein established the presence of the rheumatoid factor paraprotein in the deposits. These observations strongly suggest that complexes consisting of IgM kappa rheumatoid factor, IgG, and complement initiated the renal damage. Therefore, demonstrable serum rheumatoid factor activity in patients with B cell neoplasms should be considered a contraindication to the administration of intravenous gamma globulin.