Pretransplant Donor-Specific Anti-HLA Antibodies and the Risk for Rejection-Related Graft Failure of Kidney Allografts

Abstract

Background. The presence of donor-specific antibodies (DSAs) against HLA before kidney transplantation has been variably associated with decreased long-term graft survival. Data on the relation of pretransplant DSA with rejection and cause of graft failure in recipients of donor kidneys are scarce. Methods. Patients transplanted between 1995 and 2005 were included and followed until 2016. Donor-specific antibodies before transplantation were determined retrospectively. For cause, renal transplant biopsies were reviewed. Results. Pretransplant DSAs were found in 160 cases on a total of 734 transplantations (21.8%). In 80.5% of graft failures, a diagnostic renal biopsy was performed. The presence of pretransplant DSA (DSApos) increased the risk of graft failure within the first 3 months after transplantation (5.2% vs. 9.4%) because of rejection with intragraft thrombosis (p<0.01). One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years (9% DSAneg vs. 15% DSApos, p=0.01) with significant decreased graft survival at 10 years (79% DSAneg vs. 69% DSApos, p=0.02). This could largely contribute to an increased graft loss because of antibody-mediated rejection in the DSApos group. The incidence and graft loss because of T cell-mediated rejection was not affected by the presence of pretransplant DSA. Conclusions. Pretransplant DSAs are a risk factor for early graft loss and increase the incidence for humoral rejection and graft loss but do not affect the risk for T cell-mediated rejection.

Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation

“…While the majority of acute T cell mediated rejections occur within the first 3-6 months after transplantation, the incidence declines to virtually zero by 3-5 years post kidney transplantation (KT) (1). This decreased risk is thought to arise from a gradual decrease in alloreactivity of T-cells to donor antigen while response to alloantigen of a third party is retained.…”

Risk factors for rejection after deceased donor kidney transplantation: a mono-institutional analysis of paired kidneys

“…Traditionally, re-transplantation, grafts from deceased donor and high level of panel reactive antibody (PRA) have been reportedly associated with increased risk of graft loss and rejection after transplantation [11,12]. In current cohort, these risk factors were also evaluated and none of them demonstrated signi cant relevance with rejection in multivariate analysis.…”

Delayed Graft Function and Acute Rejection in Kidney Transplant Patients with Positive Panel-Reactive Antibody and Negative Donor-Specific Antibodies

“…The patients who received desensitization with plasmapheresis and low-dose intravenous immunoglobulin before kidney transplantation experienced successful transplantation. Betjes et al (5) confirmed that the presence of DSA against HLA before kidney transplantation was a risk factor for early graft rejection (mostly AMR). The above results have led nephrologists to believe that highly sensitized patients would increase the chances of successful kidney transplantation.…”

“…DGF and AR post-transplantation usually appear in highly sensitized patients with positive PRA or positive crossmatch (5,19,20). We had two patients whose hyperacute rejection was related to positive PRA and needed to come back to use hemodialysis after transplanted nephrectomy ( Figure 2).…”

“…Antibody-mediated rejection (AMR) usually leads to the loss of the graft. Transplantation across human leukocyte antigen (HLA) barriers, including positive PRA can be a risk factor for acute humoral rejection and worsening transplant results (4)(5)(6).…”