title: Membranoproliferative glomerulonephritis and circulating cryoglobulins.
abstract: BACKGROUND
  Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN.
  
  
  METHODS
  Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease.
  
  
  RESULTS
  In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative 'idiopathic' MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis.
  
  
  CONCLUSIONS
  Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.
authors.affiliation: Nephrology Center, Toranomon Hospital, Kajigaya, 1-3-1, Takatsu, Kawasaki, Kanagawa, 212-0015, Japan.
authors.forename: Rikako
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.forename: Eiko
authors.initials: E
authors.lastname: Hasegawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamanouchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayami
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawa
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D003165:Complement System Proteins / Q000032:analysis; D003449:Cryoglobulinemia / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy / Q000821:virology; D003450:Cryoglobulins / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000276:immunology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003450:Cryoglobulins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003165:Complement System Proteins