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.

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.