Relationship Between Cryoglobulinemia-associated Nephritis and HCV Infection

Dario Roccatello; Osvaldo Giachino; Elisa Menegatti; Simone Baldovino


Expert Rev Clin Immunol. 2008;4(4):515-524. 

In This Article

Possible Relationships Between HCV Infection & the Extent of Organ Involvement in MC: The Case of Renal Disease

Cryoglobulinemic nephritis is a unique type of nephropathy that is undoubtedly pathogenetically related to HCV infection. Case reports and even small series of presumed HCV-related noncryoglobulinemic nephropathies, specifically those with membranoproliferative patterns, are often misleading and lack adequate cryoglobulin-detection procedures or electron microscopy studies of renal histology. Thus, the role of cryoglobulins in promoting tissue damage in these cases cannot be ruled out with certainty. The relationship between HCV infection and cryoglobulinemic-associated nephritis was specifically addressed in a recent multicenter study that described the clinical characteristics, the etiology as related to viral specificities and the outcome of the biggest cohort of cryoglobulinemic GN patients ever examined worldwide.[3]

In this report, approximately 88% of cases had been infected with HCV, with genotype 1b being more frequent than genotype 2 (55 vs 43%). Only 3% of GN patients had been exposed to HBV (generally occurring as a coinfection). Over the last few years, several attempts have been made to identify an etiologic agent in the small sample of HCV noninfected patients. At first, GB virus C, another member of the Flaviviridae family, was identified as the possible agent in these cases,[9] but initial observations were not confirmed.[10] The evidence for a role of the TT virus, a DNA hepatotropic virus, is limited to coinfectious conditions.[11]

Besides the hepatic involvement, no clinical or laboratory differences could be detected between HCV-positive and HCV-negative cryoglobulinemic patients with nephritis in the multicenter study. This differs from what was observed in rheumatologic cases.[12] Some genetic markers were identified; DRB1*11 was found to be associated with nephritic involvement, while DRB1*15 was found to be protective against the development of nephritis. The prevalence of type II cryoglobulins was significantly higher in nephritic patients than in non-nephritic controls (74 vs 27%), showing that clonal restriction is probably important in renal involvement.[3]

Despite the variety of clinical presentations, diffuse membranoproliferative GN was the most prevalent histologic pattern (83%). Although both hematuria and hypertension were equally distributed among the various histologic groups, serositis, hepatosplenomegaly, leukopenia, peripheral neuropathy and cardiac involvement were only observed in the membranoproliferative pattern. Moreover, patients with diffuse membranoproliferative GN showed stronger C4 hypocomplementemia and higher levels of proteinuria.

Significant prognostic variables included age, male gender, creatinine and proteinuria at the time of renal biopsy, number of syndromic relapses and poor blood pressure control. Survival at 10 years was approximately 80%. Kaplan-Meier survival curves were worsened by basal creatinine values of more than 1.5 mg/dl (133 µmol/l). Cardiovascular disease was the cause of death in more than 60% of cases.


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