Kidney and liver involvement in cryoglobulinemia

Semin Nephrol. 2002 Jul;22(4):309-18.


Cryoglobulinemia is a pathological condition characterized by the presence in the blood of a group of proteins (cryoglobulins) showing the common property of precipitating from cooled serum. Mixed cryoglobulins (MCs) are composed of a polyclonal immunoglobulin G (IgG) bound to another immunoglobulin that acts as an anti-IgG rheumatoid factor; 2 types of MCs can be identified. The origin is not clear in 30% of all MCs, and this subset of cryoglobulinemias is called "essential." The great majority (up to 90%) of patients with essential MC (EMC) of both types has been related to HCV infection. The renal involvement in essential MC has been observed in 2% to 50% of patients in reported series. A well-characterized pattern of glomerular disease termed "cryoglobulinemic glomerulonephritis" is present in individuals with type-II EMCs in serum and IgMk RF being the most frequent monoclonal component. Aspecific and infrequent glomerular lesions occur in EMC patients with type III cryoglobulins. The most frequent histologic picture of cryoglobulinemic GN is that of membranoproliferative GN (MPGN) with subendothelial deposits. However, cryoglobulinemic GN may have some distinctive features that differentiate it from idiopathic type-I MPGN. Evidence of liver involvement has been found in 60% to 80% of EMC patients. Recent data support the notion that the stage of liver disease in patients with type II or III MC has association with the prevalence of cryoglobulinemia. Few controlled trials have been published on the treatment of HCV-related MC; in addition, the majority of the patients enrolled in these trials had an unclear renal involvement. Interferon (IFN) is an effective drug for the treatment of patients with HCV-associated MC and cryoglobulinemic GN. In the presence of acute cryoglobulinemic GN, IFN does not prevent progression of renal damage; combination therapy with cytotoxic ad anti-inflammatory drugs, and sometimes plasma exchange, is recommended. Prospective controlled trials are underway on this purpose.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Cryoglobulinemia / complications*
  • Cryoglobulinemia / physiopathology
  • Cryoglobulinemia / therapy
  • Cryoglobulinemia / virology
  • Hepatitis C / complications*
  • Hepatitis C / therapy
  • Humans
  • Interferon-alpha / therapeutic use
  • Kidney Diseases / complications*
  • Kidney Diseases / therapy
  • Liver Diseases / complications*
  • Liver Diseases / therapy


  • Antiviral Agents
  • Interferon-alpha