Cryoglobulinemic glomerulonephritis: an extrahepatic manifestation of hepatitis C virus (HCV) infection

A 66-year-old woman was admitted to our Department for evaluation of a nephrotic syndrome. Physical examination revealed ankle edema, palpable purpura of the legs and hypertension. There was no hepatosplenomegaly. The main laboratory findings were haemoglobin 11.4 g/dl, serum creatinine 1.4 mg/dl, proteinuria 3.5 g/day with reduced serum albumin (3.1 g/dl), rheumatoid factor (RF) activity 125 IU/ml, and serum C4 levels 2.3 mg/dl. Cryocrit was 24%, with type II (IgG-IgM-κ) cryoglobulins. The patient was positive for HCV antibodies and serum HCV RNA; the genotype was 1b. A percutaneous renal biopsy showed a cryoglobulinemic membranoproliferative glomerulonephritis with moderate histologic severity. The primary goal in patients with mild-to-moderate disease is viral clearance, so combination therapy with interferon-α (3 MU thrice weekly) and ribavirin (800 mg/day) was started. Twelve weeks later, serum HCV RNA had disappeared, a result that was confirmed at the end of antiviral therapy in week 48, and during the post-treatment follow-up. Proteinuria returned to the normal range, cryoglobulins decreased to undetectable levels and serum C4 levels normalized. RF activity decreased, but remained above normal. The message provided by this illustrative case is that antiviral therapy represents the first-line treatment for HCV-related cryoglobulinemic patients with mild-to-moderate kidney involvement, because it provides the best chance of viral clearance and subsequent disease improvement