Membranoproliferative Glomerulonephritis Associated with Hepatitis C Virus Infection
Richard J. Johnson, David R. Gretch, Hideaki Yamabe, Jaime Hart, Carlos E. Bacchi, Peter Hartwell, William G. Couser, Lawrence Corey, Mark H. Wener, Charles E. Alpers, and Richard Willson
Background and Methods Hepatitis C virus (HCV) infection causesboth acute and chronic liver disease and is also associatedwith mixed cryoglobulinemia. Whether HCV is also associatedwith renal disease, as is the hepatitis B virus, is not known.We describe the clinical, pathologic, virologic, and immunologicfeatures of eight patients with HCV infection who were referredto nephrologists for glomerulonephritis. Four patients weretreated with interferon alfa.
Results All eight patients had proteinuria, and seven had decreasedrenal function. Renal biopsy in all patients revealed membranoproliferativeglomerulonephritis, characterized by the deposition of IgG,IgM, and C3 in glomeruli. Electron microscopy of the biopsyspecimens showed cryoglobulin-like structures in three of fourpatients. All eight patients had HCV RNA detected in their serum,elevated serum aminotransferase concentrations, and hypocomplementemia,and the majority had cryoglobulins and circulating immune complexesin their serum. Cryoprecipitates from the three patients whowere tested contained HCV RNA and IgG anti-HCV antibodies tothe nucleocapsid core antigen (HCVc or c22-3). IgM rheumatoidfactors, present in all patients, bound anti-HCV IgG in allsix patients tested. Four patients received interferon alfafor 2 to 12 months; all had evidence of decreased HCV replicationand improvement of their renal and liver disease.
Conclusions Chronic HCV infection is associated with cryoglobulinemiaand membranoproliferative glomerulonephritis. The pathogenesisis unknown, but may relate to deposition within glomeruli ofimmune complexes containing HCV, anti-HCV IgG, and IgM rheumatoidfactors.
Source Information
From the Divisions of Nephrology and Gastroenterology, Departments of Medicine (R.J.J., J.H., P.H., W.G.C., L.C., M.H.W., R.W.), Laboratory Medicine (D.R.G., L.C., M.H.W.), and Pathology (C.E.B., C.E.A.), University of Washington Medical Center, Seattle, and the Division of Nephrology, Department of Medicine, Hirosaki University School of Medicine, Hirosaki, Japan (H.Y.).
Address reprint requests to Dr. Johnson at the Division of Nephrology, BB-1257 Health Sciences, University of Washington Medical Center, Seattle, WA 98195.
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