9 Renal Involvement in Essential Mixed Cryoglobulinemia

Up to the end of the 1980s, the cause of about 30% of both type II and III mixed cryoglobulinemias (MC) in patients was not known, and this subgroup of patients were referred to as having essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia was characterized clinically by systemic signs, mainly purpura, arthralgias, and fever, together with hepatic, neurologic, and renal symptoms. During this decade, antibodies against hepatitis C virus (HCV) antigens and HCV RNA (which is a marker of active viremia) have been detected in the serum of up to 90% of these patients. Only when a monoclonal rheumatoid factor, usually an immunoglobulin Mk (IgMk), is the anti-IgG component of the mixed cryoglobulinemia (type II MC) does this distinctive glomerular and vascular involvement of the kidney occur. The most frequent histologic picture, especially in the acute stages, is a membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits, with some characterizing features both by light and electron microscopy. However, a less distinctive picture of lobular MPGN is found at biopsy in 20% of patients, and of a mesangioproliferative glomerulonephritis in another 20%. In all cases, the two components of MC, IgG, and IgM, together with complement, are found by immunofluoroscopy. The clinical picture varies during the long-term course of the disease, being characterized by periods of temporary reactivation (nephritic or nephrotic syndrome, sometimes with rapidly occurring renal insufficiency) and long-lasting periods of partial remission. Only infrequently does end-stage renal failure develop; however, mortality as a result of the other complications of the systemic disease (mainly cardiovascular) is rather frequent. Giuseppe D’Amico Franco Ferrario