title: Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts.
abstract: In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.
authors.affiliation: Department of Nephrology, Ciutat Sanitària i Universitària de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: S
authors.initials: S
authors.lastname: Gil-Vernet
authors.forename: G
authors.initials: G
authors.lastname: Ercilla
authors.forename: D
authors.initials: D
authors.lastname: Seron
authors.forename: M
authors.initials: M
authors.lastname: Carrera
authors.forename: J
authors.initials: J
authors.lastname: Bas
authors.forename: J
authors.initials: J
authors.lastname: Torras
authors.forename: J
authors.initials: J
authors.lastname: Alsina
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyó
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D003449:Cryoglobulinemia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003450:Cryoglobulins / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018937:Hepatitis C Antibodies / Q000032:analysis; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D011863:Radioimmunoassay; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D003450:Cryoglobulins; D018937:Hepatitis C Antibodies; D012367:RNA, Viral