BACKGROUND: Live donor kidney transplantation is considered the optimal choice for renal replacement therapy, providing established benefits, such as superior patient survival and improved quality of life. However, immunological challenges, including ABO blood group incompatibility and, particularly, donor-specific HLA antibodies, may impact long-term outcomes considerably or even prevent safe direct transplantation with the intended donor.
METHODS: In this review, the authors discuss kidney paired donation (KPD) as a viable strategy to overcome immunological barriers to living donation through organ exchanges. We thereby lay special focus on the Czech-Austrian transnational KPD program.
RESULTS: While the benefits of KPD programs are well established for adult recipients, recent data suggest that this may hold true also for pediatric patients. Complex algorithms, considering factors like the intricate patterns of HLA sensitization, play a pivotal role in predicting suitable matches, but for pediatric patients also non-immunological factors including age and weight match may play a role. As pool size proves crucial for program efficacy, several countries in Europe have now initiated transnational collaborations to maximize match rates. Among those, the Czech-Austrian transnational joint program, established in 2015 and now expanded to a cooperation with the Israel transplant program to further increase transplant rates, represents a successful example.
CONCLUSIONS: KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.

暂无摘要。

We report a case of antibody-mediated rejection treated with the human CD38 monoclonal antibody daratumumab in a 58-year-old female patient with end-stage kidney disease due to autosomal dominant polycystic kidney disease who received an ABO- and human leukocyte antigen antibody-incompatible living donor kidney transplant. The patient experienced an episode of severe antibody-mediated rejection within the first week of transplantation. Blood-group-antibody selective immunoadsorption in combination with administration of four doses of daratumumab (each 1800 mg s.c.) led to a persistent decrease of ABO- and more interestingly donor-specific human leukocyte antigen antibody reactivity and resulted in clinical and histopathological remission with full recovery of graft function, which has remained stable until post-transplant day 212. This case illustrates the potential of targeting CD38 in antibody-mediated rejection.

OBJECTIVE: Despite an increase in the rate of successful live donor renal transplantation done annually, the number of potential recipients with acceptable donors is relegated to the ever-expanding cadaver-donor waiting list due to sensitization to human leukocyte antigen (HLA) antibodies. If not sufficiently suppressed, these preformed HLA antibodies can trigger antimicrobial resistance (AMR) and early graft loss. To ameliorate this situation, various desensitization treatments are administered to provide a survival benefit to highly sensitized patients.
METHODS: One hundred and six patients in the time frame of January 2017 to March 2019 were included in the study group. The desensitization protocol included therapeutic plasma exchange and administration of low-dose intravenous immunoglobulin (100 mg/kg per therapeutic plasma exchange (TPE) session) to highly sensitized patients (treatment group) who subsequently underwent renal transplantation after negative pre-transplant Centers for Disease Control and Prevention Luminex crossmatch (CDC/LumXM). We compared graft survival rates between the group undergoing desensitization (treatment group) and matched control group of patients that underwent HLA-compatible transplantation.
RESULTS: In the treatment group, Kaplan-Meier analysis estimates an average rate of patient graft survival of 95.2% at 3 years post-transplant, as compared with the rate of 86.9% in the same time frame for the control-matched group (p < 0.05 for both comparisons).
CONCLUSIONS: Desensitization treatment with TPE before live donor renal transplantation in the case of patients with HLA sensitization provides better survival benefits along with monitoring for donor-specific antibodies (DSAs) and other infections, rather than waiting for a compatible organ donor. The data lays out evidence that desensitization treatments can assist overcome HLA incompatibility barriers in live donor renal transplantation.

Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome. ABMR rates were highest among patients with positive pretransplant FCXM vs. FCXM-negative (76 vs. 18.7%, p < 0.001) and with donor-specific antibody mean fluorescence intensity (DSA MFI) > 5,000 vs. <5,000 (54.5 vs. 28%, p = 0.01) despite desensitization. In univariable Cox regression, FCXM positivity, retransplantation, recipient gender, immunodominant DSA MFI, DSA number, and peak panel reactive antibodies were found to be associated with ABMR occurrence. In multivariable Cox regression adjusted for desensitization treatment (AUC = 0.810), only FCXM positivity (HR = 4.6, p = 0.001) and DSA number (HR = 1.47, p = 0.039) remained significant. In conclusion, our data suggest that pretransplant FCXM and DSA number, but not DSA MFI, are independent predictors of ABMR in patients who received peritransplant desensitization.

With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook for \"untransplantable\" kidney transplantation candidates has never been more promising. The Kidney Allocation System prioritized compatible matches for candidates with calculated panel-reactive antibody levels of 98%, 99%, or 100% and broadened allocation of non-A1 and non-A1-B subgroup kidneys to blood group type B candidates. Concurrently, the growth of kidney paired donation programs and use of incompatible transplantation as part of kidney paired donation to achieve \"more compatible\" kidney transplantation has improved options for candidates with an incompatible living donor. Finally, advances in desensitization and immunosuppression have strengthened the ability to manage donor-specific antibodies and antibody-mediated rejection. Although no patient should be labeled \"untransplantable\" due to blood group type or donor-specific antibody, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. In this Perspective, we consider blood group type ABO incompatibility, HLA antigen incompatibility, antibody-mediated rejection, kidney paired donation, and recent developments in incompatible transplantation in more depth and recommend an approach to the sensitized candidate.

The notable evolution of heart transplant (HTX) has paralleled the capacity of diagnosing rejection and, consequently, initiating timely treatment. Acute cellular rejection, diagnosed by endomyocardial biopsy, is the most frequent in the first 6 months after HTX. HLA matching is not routinely performed in HTX due to the absence of consensus regarding its usefulness. However, the use of HLA typing might be underscored if it could predict an increased risk of rejection. Therefore, the aim of this study was to evaluate, at a public cardiology center in Brazil, the association between HLA mismatches and the incidence of acute cellular rejection in the first 6 months after HTX. Data were obtained from hospital records and from the National Transplant System. Overall, there was no association between the number of HLA mismatches and the frequency of acute cellular rejection, but there was a tendency toward a higher incidence of rejection with HLA-DR incompatibility.

Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m2 ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption). By day 0, 17 of the 27 DSAs had become undetectable. After 19 (3-51) months, patient- and graft-survival rates were 100% and 91.6%, respectively. One patient had an acute humoral rejection whereas three had a chronic antibody-mediated rejection (CAMR). At the last follow-up, kidney biopsies were nearly normal in seven cases (58.3%) and renal function was excellent except for the three cases of CAMR. Four patients had a BK virus infection. We conclude that ABOi/HLAi living-kidney transplantation is a reasonable option for highly sensitized patients.

New approaches to increase kidney transplantation rates through expansion of live donor kidney transplantation have become necessary due to ongoing shortage of deceased donor organs. These strategies include desensitization in antibody-incompatible transplants to overcome the barrier of blood group incompatibility or human leucocyte antigen antibodies between recipient and donor and kidney paired donation (KPD) programmes. In KPD, a kidney transplant candidate with an incompatible live donor joins a registry of other incompatible pairs in order to find potentially compatible transplant solutions. To match the largest possible number of donor-recipient pairs while minimizing immunologic risk, KPD programmes use sophisticated algorithms to identify suitable matches with simultaneous two-way or more complex multi-way exchanges as well as including non-directed anonymous donors to start a chain of compatible transplantations. Because of the significant immunologic barriers when fewer donor options are available, the optimal solution for difficult-to-match, highly sensitized patients is access to more potential donors using large multi-centre or national KPD registries. This review focuses on the first 4 years of experience with the Australian multi-centre KPD programme that was established in October 2010.

Due to the ongoing shortage of deceased-donor organs, novel strategies to augment kidney transplantation rates through expanded living donation strategies have become essential. These include desensitization in antibody-incompatible transplants and kidney paired donation (KPD) programs. KPD enables kidney transplant candidates with willing but incompatible living donors to join a registry of other incompatible pairs in order to find potentially compatible transplant solutions. Given the significant immunologic barriers with fewer donor options, single-center or small KPD programs may be less successful in transplanting the more sensitized patients; the optimal solution for the difficult-to-match patient is access to more potential donors and large multicenter or national registries are essential. Multicenter KPD programs have become common in the last decade, and now represent one of the most promising opportunities to improve transplant rates. To maximize donor-recipient matching, and minimize immunologic risk, these multicenter KPD programs use sophisticated algorithms to identify optimal match potential, with simultaneous two-, three- or more complex multiway exchanges. The article focuses on the recent progresses in KPD and it also reviews some of the differences and commonalities across four different national KPD programs.