title: Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan. Electronic address: rikako64@toranomon.gr.jp.
authors.forename: Rikako
authors.initials: R
authors.lastname: Hiramatsu
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan. Electronic address: ubara@toranomon.gr.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawa
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawada
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Imafuku
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Mise
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamanouchi
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hayami
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suwabe
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.affiliation: Nephrology Center, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan; Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.affiliation: Department of Pathology, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan; Department of Pathology, Yokohama City University, Graduate School of Medicine, Yokohama, 236-0004, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Pathology, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Hematology, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wake
authors.affiliation: Department of Hematology, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005260:Female; D005455:Fluorescent Antibody Technique; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007564:Japan; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D007166:Immunosuppressive Agents
keywords: Allogeneic hematopoietic cell transplantation; Anti-PLA2R autoantibody; Chronic graft-versus-host disease; Membranoproliferative pattern glomerulonephritis; Membranous glomerulonephritis; Umbilical cord blood transplantation; Unrelated bone marrow transplantation