title: Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches.
abstract: Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. Protocol biopsies within 1 year revealed subclinical CAMR in 36% of HLA-I, 5% of ABO-I and 3% of ABO-Id/C, although clinical acute AMR was observed in 8%, 3% and 1%, respectively. The incidence of CAMR was not different between class I and class II DSA. Most of class I DSA (94%) changed to negative 1 year after RTx, whereas 77% of class II DSA remained positive. In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR.
authors.affiliation: Department of Transplant Surgery and Nephrology, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya 466-8650, Japan. yama335@gmail.com
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Yamanaga
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Watarai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsujita
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hiramitsu
authors.forename: Koji
authors.initials: K
authors.lastname: Nanmoku
authors.forename: Norihiko
authors.initials: N
authors.lastname: Goto
authors.forename: Asami
authors.initials: A
authors.lastname: Takeda
authors.forename: Kunio
authors.initials: K
authors.lastname: Morozumi
authors.forename: Akio
authors.initials: A
authors.lastname: Katayama
authors.forename: Hiroh
authors.initials: H
authors.lastname: Saji
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Uchida
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000920:Antibody-Dependent Cell Cytotoxicity; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000378:metabolism; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010956:Plasmapheresis; D011183:Postoperative Complications / Q000276:immunology*; D012189:Retrospective Studies; D012306:Risk; D000069283:Rituximab; D013997:Time Factors; D019172:Transplantation Conditioning
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D000069283:Rituximab; D009173:Mycophenolic Acid
keywords: ABO blood type identical/compatible; ABO blood type incompatible; ABO-I; ABO-Id/C; AMR; AUC; CAAMR; CAMR; CDCXM; CI; CSA; DFPP; DSA; FCXM; HLA; HLA-I; HLA-incompatible; IVIG; MFI; MMF; OR; RTx; SAFB; TAC; antibody-mediated rejection; area under the curve; chronic AMR; chronic active AMR; complement-dependent cytotoxicity (CDC) crossmatch; confidential interval; cyclosporine; donor-specific HLA antibodies; double filtration plasmapheresis; flow cytometry crossmatch; human leukocyte antigen; intravenous immunoglobulin; mean fluorescence intensity; mycophenolate mofetil; odds ratio; renal transplantation; single HLA antigen-coated synthetic flow beads; tacrolimus