Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically. Hence, this Delphi methodology was used to reach a consensus from a multi-disciplinary team (MDT) of experts from 15 countries on the management of HS patients undergoing imlifidase HLAi from a deceased donor (DD) KTx. This Delphi consensus provides clinical practice guidance on the use of imlifidase in the end-to-end management of HS patients undergoing an HLAi DD KTx and supports centers in the development of guidelines for the utilization and integration of imlifidase into clinical practice.

• MeSH
• dárci tkání * MeSH
• delfská metoda * MeSH
• desenzibilizace imunologická * metody   MeSH
• HLA antigeny * imunologie   MeSH
• imunoglobulin G MeSH
• konsensus * MeSH
• lidé MeSH
• rejekce štěpu prevence a kontrola   imunologie   MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• beta-laktamasy MeSH
• cefalosporiny terapeutické užití   MeSH
• dospělí MeSH
• kombinace léků piperacilin a tazobactam terapeutické užití   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• příjemce transplantátu statistika a číselné údaje   MeSH
• průzkumy a dotazníky MeSH
• Pseudomonas aeruginosa účinky léků   izolace a purifikace   MeSH
• pyelonefritida * farmakoterapie   mikrobiologie   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: The median kidney transplant half-life is 10-15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980-2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies "retransplant" versus "remain waitlisted with maintenance dialysis" are reported for different waiting times after first graft loss. RESULTS: Second kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, -14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively. CONCLUSIONS: Second kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

• MeSH
• časové faktory MeSH
• chronické selhání ledvin mortalita   chirurgie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• opakovaná terapie statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• seznamy čekatelů * MeSH
• transplantace ledvin statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

• MeSH
• ledviny MeSH
• lidé MeSH
• odběr tkání a orgánů MeSH
• průzkumy a dotazníky MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• žijící dárci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články 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
• ledviny MeSH
• lidé MeSH
• retrospektivní studie MeSH
• transplantace ledvin * MeSH
• žijící dárci MeSH
• získávání tkání a orgánů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Rakousko MeSH

Background: Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. Here, we investigated whether the intrinsic strength of classical pathway and alternative pathway (AP) relates to the pathogenicity of DSA. Methods: Classical pathway and AP high-activity genotypes were defined according to C4 gene copy number and the presence of functional polymorphisms in C3 (C3102G), factor B (fB32R), and factor H (fH62V) genes. Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients (antibody-mediated rejection [AMR], n = 47) identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days posttransplantation. Associations with long-term graft survival were evaluated in a larger kidney transplant cohort (n = 660) not enriched for a specific type of rejection. Results: In the cohort of DSA-positive subjects, the number of C4 gene copies was related to C4 protein levels in serum and capillary C4d staining, but not AMR activity. Patients with a high-activity AP complotype, which was associated with complement consumption in serum, showed enhanced microcirculation inflammation (median glomerulitis plus peritubular capillaritis score, 2 [interquartile range, 0-4 versus 1 0-2]; P = 0.037). In the larger transplant cohort, this complotype was associated with a slightly increased risk of graft loss (hazard ratio, 1.52; 95% confidence interval, 1.02-2.25; P = 0.038 and multivariable Cox model, 1.55; 1.04-2.32; P = 0.031). Conclusions: Our study suggests a contribution of complement genetics to the phenotypic presentation of AMR. Future studies will have to clarify whether a possible association of AP strength with graft survival relates to enhanced antibody-triggered injury.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Existing guidelines on the evaluation and preparation of recipients for kidney transplantation target the entire spectrum of patients with end-stage renal disease. Within the ERA-EDTA Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) Working Group, it was proposed that in a subset of relatively young patients (<40 years) without significant comorbidities (such as diabetes or cardiovascular disease), the work-up for transplantation could be restricted to a small set of tests. METHODS: Aiming for agreement between transplant centres across Europe, we surveyed the opinion of 80 transplant professionals from 11 European states on the composition of a minimal work-up. RESULTS: We show that there is a wide agreement among European experts that the work-up for kidney transplantation of the low-risk candidate, as opposed to the standard risk candidate, could include a limited number of investigations. However, there is some disagreement regarding the small number of diagnostic procedures, which is related to geographical location within Europe and the professional background of respondents. CONCLUSIONS: Based on the results of the survey, published guidelines and expert meetings by the DESCARTES Working Group, we have formulated a proposal for the work-up of low-risk kidney transplant candidates.

• MeSH
• chronické selhání ledvin diagnóza   chirurgie   MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předoperační péče * MeSH
• průzkumy zdravotní péče MeSH
• směrnice pro lékařskou praxi jako téma normy   MeSH
• transplantace ledvin výchova   normy   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

Current proposals for waiting times for a renal transplant after malignant disease may not be appropriate. New data on malignancies in end-stage renal disease and recent diagnostic and therapeutic options should lead us to reconsider our current practice.

• MeSH
• čas zasáhnout při rozvinutí nemoci normy   MeSH
• chronické selhání ledvin terapie   MeSH
• lidé MeSH
• nádory patofyziologie   MeSH
• seznamy čekatelů * MeSH
• směrnice pro lékařskou praxi jako téma normy   MeSH
• transplantace ledvin statistika a číselné údaje   MeSH
• výběr pacientů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The introduction of HLA matching of donors and recipients was a breakthrough in kidney transplantation. However, half of all transplanted kidneys still fail within 15 years after transplantation. Epidemiological data suggest a fundamental role of non-HLA alloimmunity. METHODS: We genotyped 477 pairs of deceased donors and first kidney transplant recipients with stable graft function at three months that were transplanted between Dec 1, 2005, and April 30, 2015. Genome-wide genetic mismatches in non-synonymous single nucleotide polymorphisms (nsSNPs) were calculated to identify incompatibilities in transmembrane and secreted proteins. We estimated the association between nsSNP mismatch and graft loss in a Cox proportional hazard model, adjusting for HLA mismatch and clinical covariates. Customised peptide arrays were generated to screen for antibodies against genotype-derived mismatched epitopes in 25 patients with biopsy-confirmed chronic antibody-mediated rejection. FINDINGS: 59 268 nsSNPs affecting a transmembrane or secreted protein were analysed. The median number of nsSNP mismatches in immune-accessible transmembrane and secreted proteins between donors and recipients was 1892 (IQR 1850-1936). The degree of nsSNP mismatch was independently associated with graft loss in a multivariable model adjusted for HLA eplet mismatch (HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, and HLA-DR). Each increase by a unit of one IQR had an HR of 1·68 (95% CI 1·17-2·41, p=0·005). 5-year death censored graft survival was 98% in the quartile with the lowest mismatch, 91% in the second quartile, 89% in the third quartile, and 82% in the highest quartile (p=0·003, log-rank test). Customised peptide arrays verified a donor-specific alloimmune response to genetically predicted mismatched epitopes. INTERPRETATION: Genetic mismatch of non-HLA haplotypes coding for transmembrane or secreted proteins is associated with an increased risk of functional graft loss independently of HLA incompatibility. As in HLA alloimmunity, donor-specific alloantibodies can be identified against genotype derived non-HLA epitopes. FUNDING: Austrian Science Fund, WWTF (Vienna Science and Technology Fund), and Ministry of Health of the Czech Republic.

• MeSH
• alografty imunologie   MeSH
• celogenomová asociační studie MeSH
• dárci tkání MeSH
• dospělí MeSH
• HLA antigeny imunologie   MeSH
• hodnocení výsledků zdravotní péče MeSH
• jednonukleotidový polymorfismus MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežívání štěpu * MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• protilátky imunologie   MeSH
• rejekce štěpu epidemiologie   imunologie   MeSH
• studie případů a kontrol MeSH
• testování histokompatibility statistika a číselné údaje   MeSH
• transplantace ledvin statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation. Here, we have summarized the main knowledge and the main challenges of these seven topics with the aim to provide transplant professionals at large with key bullet points to successfully understand these new concepts.

• MeSH
• alokace zdrojů * MeSH
• chronické selhání ledvin terapie   MeSH
• fokálně segmentální glomeruloskleróza prevence a kontrola   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé MeSH
• transplantace ledvin metody   MeSH
• výběr pacientů * MeSH
• získávání tkání a orgánů normy   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH