Kidney transplantation in highly sensitized recipients

Abstract

In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.

Combined impact of the inter and intra-patient variability of tacrolimus blood level on allograft outcomes in kidney transplantation

“…Out of these, patients who experienced allograft loss within 90 days (n = 7), who were sensitized to donor human leukocyte antigen (HLA) before KT (n = 126), and whose CDR calculation was not possible due to missing TAC-C0 results (n = 14) were excluded from the present study. Sensitization to donor HLA was defined as positivity to the complement-dependent cytotoxicity cross-match test, flow cytometry cross-match test, or the presence of DSA with a median fluorescence intensity (MFI) of ≥ 1,000 before KT ( 18 ). Ultimately, 1,080 patients were included in the study, the last follow-up date was December 31, 2020, and the mean follow-up duration of these patients was 5.7 years.…”

Impact of low-level donor-specific anti-HLA antibody on post-transplant clinical outcomes of kidney transplant recipients

“…Pre-transplant DSZ protocol. Our center's DSZ protocol has been presented previously 12,32,35 . Brie y, we used strati ed protocol according to the baseline MFI value.…”

“…Therefore, currently used desensitization (DSZ) techniques are based on the MFI value of HLA-DSA in addition to XM test result [10][11][12] . However, when LSA assay is positive and XM test is negative, the clinical relevance of HLA-DSA on post-transplant clinical outcomes remains controversial [13][14][15][16] .…”

Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients

“…This improvement allows for more detailed risk stratification for the prediction of ABMR or allograft failure than a traditional XM test [ 8 – 10 ]. Therefore, current desensitization strategies are based on the MFI values of HLA-DSA and XM test results [ 11 – 13 ]. However, previous studies on the clinical impact of HLA-DSA on posttransplant clinical outcomes have shown contradictory results in case the LSA assay is positive and the XM test negative [ 14 – 17 ]; therefore, its clinical impact remains unclear.…”