The cryoglobulinemic glomerulonephritis associated with hepatitis C virus infection

Mixed cryoglobulinemia (MC) and glomerulonephritis (GN) are the most important extrahepatic manifestations of hepatitis C virus (HCV) infection. The GN occurring in HCV infection is predominantly associated with MC and almost always takes the form of a membranoproliferative GN (MPGN) with endoluminal thrombi and subendothelial immune-deposits displaying the classic cryoglobulin-like substructure. Clinically, cryoglobulinemic GN may present with isolated urinary abnormalities, overt nephritic (20-30%) or nephrotic syndrome (20%) with a variable progression towards chronic renal insufficiency. Although terminal renal failure requiring dialysis is rare, for patients with MC accompained by kidney involvement a poor prognosis has been reported, owing to an unusual high incidence of infection or cardiovascular disease. The renal damage might be mediated by HCV through induction of a lympho-proliferative disorder that activates the clonal expansion of IgMk-bearing B cells, leading to the formation of (HCV)-IgG-IgMk immune complexes. Although a fully satisfactory treatment is not yet available, a reasonable therapeutic strategy for HCV-infected patients with cryoglobulinemic GN could be as follows: (i) antiviral treatment alone for patients with a low-grade kidney involvement, (ii) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN.