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: Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients. METHODS: We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples. RESULTS: We identified rare variants of HOMER2 (3/36, FDR 0.0387), IQCH (5/36, FDR 0.0362), and LCN2 (3/36, FDR 0.102) in 10 tolerant patients vs. 0 controls. One patient carried a variant in both HOMER2 and LCN2. Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium, a key structure in immune responses. CONCLUSION: Rare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444.
- Publikační typ
- časopisecké články 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
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
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
- MeSH
- celogenomová asociační studie MeSH
- ledviny MeSH
- lidé MeSH
- nemoci ledvin * MeSH
- rejekce štěpu MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors, especially in those having first-degree relatives with ESRD. The study from Norway also found an increased risk of death after living donor nephrectomy, which became visible only after >15 years of post-donation follow-up. However, these findings are likely to be largely the result of an overestimation due to the confounding effect related to a family history of renal disease. DESCARTES board members emphasize the importance of optimal risk–benefit assessment and proper information to the prospective donor, which should also include recommendations on health-promoting behaviour post-donation.
BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2 receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. CONCLUSIONS: There is very limited evidence for the benefits and harms of different immunosuppression strategies in the elderly. Most of the published literature are observational studies, and randomized controlled trials are urgently needed.
- MeSH
- imunosupresiva terapeutické užití MeSH
- imunosupresivní léčba * MeSH
- inhibitory kalcineurinu MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma * MeSH
- rejekce štěpu * MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.
- MeSH
- dospělí MeSH
- homologní transplantace MeSH
- imunologická tolerance imunologie MeSH
- imunosupresivní léčba metody MeSH
- incidence MeSH
- lidé MeSH
- míra přežití trendy MeSH
- přežívání štěpu imunologie MeSH
- příjemce transplantátu * MeSH
- průzkumy a dotazníky MeSH
- rejekce štěpu epidemiologie imunologie prevence a kontrola MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
