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Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy.The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease.The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.