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. CONCLUSION: KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.

• MeSH
• Child MeSH
• Adult MeSH
• HLA Antigens immunology   MeSH
• Humans MeSH
• Kidney Transplantation * MeSH
• Living Donors * MeSH
• Tissue and Organ Procurement * MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH
• Europe MeSH

• MeSH
• ABO Blood-Group System MeSH
• Blood Group Antigens classification   MeSH
• Blood Transfusion, Autologous classification   MeSH
• Blood Preservation MeSH
• Blood Transfusion * methods   MeSH
• Humans MeSH
• Blood Group Incompatibility MeSH
• Transfusion Reaction classification   pathology   therapy   MeSH
• Blood Component Removal MeSH
• Transfusion Medicine * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant. Especially patients with rare HLA phenotypes in relation to the actual donor pool are waiting extremely long. As HLA phenotypes are different in the various European populations, we hypothesized that extension of the donor pool outside the respective allocation system will increase the chance of receiving a compatible transplant for this subgroup of highly sensitised patients. One of the objectives of the EUROSTAM project, (a Europe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches) was to develop a tool to compare the chance of transplanting HSP in different European populations with donor organs from within and outside their own donor pool. Information on the HLA type and ABO blood group of the actual donor population, as well as the acceptable mismatches of long waiting HSP were obtained from the EUROSTAM partner organizations i.e. Eurotransplant (ET), UK National Health Service Blood and Transplant (NHSBT), Barcelona, Prague and Athens. Results from simulations using the newly developed tool shows that 195 (27%) of the 724 long waiting highly sensitised patients registered at each partner organisation have increased chances of transplant in a different European donor pool. This makes a strong case for sharing kidneys between European countries for selected difficult to transplant patients.

• MeSH
• Tissue Donors MeSH
• Histocompatibility MeSH
• HLA Antigens genetics   immunology   MeSH
• Immunization MeSH
• Humans MeSH
• Transplant Recipients MeSH
• Waiting Lists MeSH
• Histocompatibility Testing methods   MeSH
• Kidney Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Editorial MeSH
• Geographicals
• Europe MeSH

• MeSH
• Anemia * etiology   therapy   MeSH
• Erythroblastosis, Fetal diagnosis   therapy   MeSH
• Rh-Hr Blood-Group System MeSH
• Humans MeSH
• Parvovirus B19, Human pathogenicity   MeSH
• Blood Group Incompatibility MeSH
• Infant, Premature MeSH
• Cause of Death MeSH
• Bone Marrow Examination MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO- and low-level HLA antibody-incompatible exchanges, including the option of altruistic donor-initiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multi-national registries to expand the full potential of KPD.

• MeSH
• Kidney MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Kidney Transplantation * MeSH
• Living Donors MeSH
• Tissue and Organ Procurement * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Austria MeSH

PURPOSE OF REVIEW: This review summarises recent developments in monitoring and immunosuppressive management in kidney transplantation. RECENT FINDINGS: Long-term kidney allograft outcomes have not changed substantially mainly as a result of acute and chronic antibody-mediated rejection. Several groups have recently attempted to determine peripheral molecular fingerprints of ongoing rejection. But while this research is promising, it is not generalised for further spreading among different cohorts. Measurements of donor-derived cell-free DNA levels in recent studies have revealed better predictive values for antibody-mediated rejection. The Molecular Microscope Diagnostic System for assessing kidney graft biopsies has been gradually introduced within clinical practice, especially in complicated cases aimed at improving histological diagnostics. Molecular studies on accommodation in ABO-incompatible transplantation have shown increased complement regulation and lower expression of epithelial transporters and class 1 metallothioneins. Additionally, in clinical studies of sensitised patients, imlifidase has been shown to enable transplantation across significant immunological barriers, while the co-stimulation blockade has been tested to prevent donor specific antibodies development. In low-risk patients, everolimus/tacrolimus-based regimens have also proven their antiviral effects in large clinical trials. SUMMARY: Recent developments in non-invasive monitoring have paved the way for the introduction of future larger clinical trials with multiple patient cohorts.

• MeSH
• Immunosuppression Therapy methods   MeSH
• Humans MeSH
• Kidney Transplantation methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: Many transfusion services determine the titer of potentially incompatible plasma-containing products by performing a one-dilution titer at their selected titer threshold. This study compared the results of immediate spin (IS) one-dilution titers determined by three methods with a reference standard method. METHODS: Plasma-containing products from group A and O donors were titered using the participant's routine IS one-dilution titer method. No time or temperature incubations were performed, and antihuman globulin reagent was not used. The samples were then tested using a reference method, which was a saline tube test with a 1-hour room temperature incubation; antihuman globulin was not used in the reference method. The results of the one-dilution titer were then compared to that obtained in the reference method. RESULTS: Nine centers participated in this study. There were 698 antibodies from 374 units tested by the manual IS tube one-dilution titer method; sensitivity was 0.88 (95% confidence interval [CI], 0.83-0.92), and specificity was 1.00 (95% CI, 0.98-1.00). There were 412 antibodies from 206 units tested by the manual and automated IS buffered gel card one-dilution titer method; sensitivity was 0.95 (95% CI, 0.91-0.98), and specificity was 0.87 (95% CI, 0.81-0.91). There were 98 antibodies from 49 units tested by an automated microplate IS one-dilution titer method; sensitivity was 0.76 (95% CI, 0.71-0.93), and specificity was 0.96 (95% CI, 0.92-0.99). All three methods had an accuracy rate of 90% or greater. CONCLUSION: The manual and automated one-dilution titer methods are suitable for screening plasma-containing units, although more evaluation of the automated microplate method might be required.

• MeSH
• ABO Blood-Group System blood   MeSH
• Indicator Dilution Techniques MeSH
• Isoantibodies blood   MeSH
• Humans MeSH
• Blood Group Incompatibility blood   MeSH
• Specimen Handling methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

• MeSH
• Safety MeSH
• Humans MeSH
• Survival Rate MeSH
• Blood Group Incompatibility MeSH
• Graft Rejection MeSH
• Rituximab MeSH
• Statistics as Topic MeSH
• Kidney Transplantation * mortality   MeSH
• Living Donors * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Meta-Analysis MeSH

BACKGROUND: Accommodation in ABO-incompatible (ABOi) transplantation and subclinical antibody-mediated rejection in HLA-incompatible (HLAi) transplantation share several morphological similarities. Because the clinical long-term outcomes differ, we hypothesized different molecular processes involved in ABOi transplantation and subclinical antibody-mediated rejection. METHODS: Using Illumina Human HT-12 v4 Expression BeadChips, the whole transcriptome was evaluated based on 3-month protocol C4d+ biopsies in otherwise stable ABOi and HLAi kidney grafts, as well as in C4d-negative HLA-compatible grafts exhibiting normal histological findings. Top differently regulated genes were further validated using real-time quantitative polymerase chain reaction in another patient cohort and complement regulatory proteins by immunohistochemistry. RESULTS: In the case of genes involved in immune response-related biological processes, ABOi and HLAi cohorts had similar transcriptomic profiles to C4d-negative controls. The majority of deregulated genes in the ABOi and HLAi groups consisted of metallothioneins and epithelial transporter genes. Increased expression of epithelial transporters (SLC4A1, SLC4A9, SLC17A3, SLC12A3, and SLC30A2) and class 1 metallothioneins (MT1F, MT1G, and MT1X) in HLAi transplantation was validated by real-time quantitative polymerase chain reaction. In comparison to controls, both incompatible cohorts were characterized by the upregulation of intrarenal complement regulatory genes. CD46 and CD59 transcripts were increased in the ABOi cohort, whereas CD46 solely in HLAi group, and CD59 protein expression was similar in both incompatible groups. CONCLUSIONS: Several epithelial transporters and metallothioneins discriminate subclinical antibody-mediated rejection in HLAi transplantation from accommodation in ABOi transplantation, which suggest different involved downstream mechanisms and increased risk of injury in HLAi settings. Metallothioneins with their antioxidative properties may help to attenuate the inflammation response induced by donor-specific anti-HLA antibody binding.

• MeSH
• ABO Blood-Group System immunology   MeSH
• Allografts immunology   metabolism   pathology   MeSH
• Biomarkers metabolism   MeSH
• Biopsy MeSH
• Adult MeSH
• HLA Antigens immunology   MeSH
• Isoantibodies immunology   MeSH
• Kidney immunology   metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Membrane Transport Proteins metabolism   MeSH
• Metallothionein metabolism   MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Blood Group Incompatibility diagnosis   immunology   pathology   MeSH
• Graft Survival immunology   MeSH
• Graft Rejection diagnosis   immunology   pathology   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Gene Expression Profiling MeSH
• Kidney Transplantation adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH

BK virus nephropathy (BKVN) is a serious opportunistic infection threatening renal function especially during the first year after transplantation. Its incidence is now on the rise and is closely related to the level of the recipient's immune system inhibition. This is more intensive with current trends in transplantation medicine, where more potent immunosuppressive protocols are used and more aggressive antirejection therapy is applied. In the absence of BK virus (BKV) specific therapy and limited treatment options for advanced BKVN, active screening of BKV replication and subsequent preemptive adjustment of immunosuppression are essential measures to prevent BKVN. However, it remains unclear how to modify immunosuppressive protocols as well as how to address initial stages of BKV replication. This comprehensive review summarizes the currently applied and not completely uniform procedures for the detection, prophylaxis and therapy of BKV replication and BKVN. The pitfalls brought by reduced immunosuppression, as a typical response to a significant viral replication or a developed BKVN, are also mentioned, particularly in the form of graft rejection. The paper also outlines the authors' experiences, and lists currently ongoing studies on the subject. The perspectives of new, especially immune-based, procedures in the treatment of complications associated with BKV infections are highlighted. Different views on the management of patients indicated for kidney re-transplantation whose previous graft failed because of BKVN are also discussed.

• MeSH
• ABO Blood-Group System MeSH
• Antiviral Agents therapeutic use   MeSH
• Early Diagnosis MeSH
• Tissue Donors MeSH
• Adult MeSH
• Microscopy, Electron MeSH
• Transplantation, Homologous MeSH
• Immunosuppressive Agents adverse effects   MeSH
• Humans MeSH
• Blood Group Incompatibility MeSH
• Kidney Diseases immunology   virology   MeSH
• Opportunistic Infections diagnosis   immunology   prevention & control   MeSH
• Polyomavirus Infections diagnosis   immunology   prevention & control   MeSH
• Transplant Recipients MeSH
• Immunity, Innate physiology   MeSH
• Virus Replication MeSH
• T-Lymphocytes immunology   MeSH
• Kidney Transplantation adverse effects   MeSH
• BK Virus * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH