title: Renal thrombotic microangiopathy associated with chronic humoral graft versus host disease after hematopoietic stem cell transplantation.
abstract: Thrombotic microangiopathy (TMA) is a known complication of hematopoietic stem cell transplantation (HSCT). The pathogenesis of TMA is controversial but considered to involve various factors such as total body irradiation, use of calcineurin inhibitors for prophylaxis against graft versus host disease (GVHD), viral infection, and GVHD. Herein we describe a case with renal TMA after HSCT, which was probably associated with antibody-mediated endothelial cell injury from chronic GVHD (termed here 'chronic humoral GVHD'). A 49-year-old man presented two years after HSCT with renal dysfunction and proteinuria but without the clinical features of TMA. Histopathological examination of renal biopsy showed chronic glomerular endothelial cell injury with double contour of the glomerular basement membrane, microthrombi and the deposition of complement split product C4d along the glomerular capillaries. Renal tubulitis and peritubular capillaritis were also noted with a multilayered basement membrane and patchy C4d deposition on peritubular capillaries. These findings resemble those of chronic antibody-mediated rejection after kidney transplantation. Furthermore, C4d deposition suggests complement activation. Although circulating anti-blood type and anti-human leukocyte antigen antibodies were not detected, the renal TMA in this case was probably associated with chronic humoral GVHD.
authors.affiliation: Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mii
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujino
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaneko
authors.forename: Kouichi
authors.initials: K
authors.lastname: Utsumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Arimi
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Tajika
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iino
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D015935:Complement C4b / Q000276:immunology; D006086:Graft vs Host Disease / Q000150:complications* / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D007674:Kidney Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D057049:Thrombotic Microangiopathies / Q000150:complications* / Q000276:immunology / Q000473:pathology
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d