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Background Donor-related malignancy is a rare complication of organ transplantation. Methods In this case series, we discuss three cases of donor-related cancers in kidney transplant recipients who were registered in our center between 1979 and 2015. They account for an incidence of 0.29% of donor-related malignancies of a total of 1015 transplanted kidney grafts (deceased and living donors). The three cases that we describe presented in different ways and with different severity, although the response to the initiated treatment was comparable. Results All three patients not only survived their cancer episode but also had a complete oncological remission and underwent successful second kidney transplantation, accounting for a 100% survival rate in our small cohort. Conclusions Despite the very low incidence of this complication, transplant clinicians must be aware of the occurrence of donor-related malignancies when selecting a donor and should be able to diagnose and treat a case of donor-related cancer. [ABSTRACT FROM AUTHOR]

Background: Preemptive kidney transplantation (PEKT) has better outcomes when compared with transplantation after dialysis. We aimed to examine trends in PEKT between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives., Methods: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around PEKT., Results: Between 2000 and 2019, 20 251 adults underwent PEKT [11 169 from living donors (LDs), 8937 from deceased donors (DDs)]. The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for LD kidney recipients (from 21% to 43%) and DD kidney recipients (from 4% to 11%). Large international differences were found. The increase in PEKT was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donoror recipient work-up. Suggested initiatives included raising awareness on the possibility of PEKT, earlier start and shorter work-up time for recipient and LD., Conclusions: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and DD kidney recipients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Hypothesis: The decision for acceptance or discard of the increasingly rare and marginal brain-dead donor kidneys in Eurotransplant (ET) countries has to be made without solid evidence. Thus, we developed and validated flexible clinicopathological scores called 2-Step Scores for the prognosis of delayed graft function (DGF) and one-year death-censored transplant loss (1y-tl) reflecting the current practice of six ET countries including Croatia and Belgium., Methods: The training set was n=620 for DGF and n=711 for 1y-tl, with validation sets n=158 and n=162. In step 1, stepwise logistic regression models including only clinical predictors were used to estimate the risks. In step 2, risk estimates were updated for statistically relevant intermediate risk percentiles with nephropathology., Results: Step 1 revealed an increased risk of DGF with increased cold ischaemia time, donor and recipient BMI, dialysis vintage, number of HLA-DR mismatches or recipient CMV IgG positivity. On the training and validation set, c-statistics were 0.672 and 0.704, respectively. At a range between 18% and 36%, accuracy of DGF-prognostication improved with nephropathology including number of glomeruli and Banff cv (updated overall c statistics of 0.696 and 0.701, respectively).Risk of 1y-tl increased in recipients with cold ischaemia time, sum of HLA-A. -B, -DR mismatches and donor age. On training and validation sets, c-statistics were 0.700 and 0.769, respectively. Accuracy of 1y-tl prediction improved (c-statistics = 0.706 and 0.765) with Banff ct. Overall, calibration was good on the training, but moderate on the validation set; discrimination was at least as good as established scores when applied to the validation set., Conclusion: Our flexible 2-Step Scores with optional inclusion of time-consuming and often unavailable nephropathology should yield good results for clinical practice in ET, and may be superior to established scores. Our scores are adaptable to donation after cardiac death and perfusion pump use., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our aim was to analyze evidence about results from HLAid living-donor recipients under different immunosuppression in the current era of immunological risk assessment., Methods: Systematic review of studies describing associations between outcomes of HLAid living-donor KT recipients according to their immunological risk and applied immunosuppression., Results: From 1351 studies, 16 (5636 KT recipients) were included in the analysis. All studies were retrospective, ten comparing immunosuppression strategies, and six immunological risk strata. Of those ten, six studies were published in 1990 or earlier and only three included tacrolimus. The evidence is poor, and the inclusion of calcineurin inhibitors does not demonstrate better results. Furthermore, only few studies describe different immunosuppression regimens according to the patient immunological risk and, in general, they do not include the assessment with new solid phase assays., Conclusions: There are no studies analyzing the association of outcomes of HLAid KT recipients with current immunological risk tools. In the absence of evidence, no decision or proposal of immunosuppression adapted to modern immunological risk assessment can be made currently by the Descartes Working Group., Competing Interests: Declaration of Competing Interest The results presented in this paper have not been published previously in whole or part. The authors of this study declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Post-transplant diabetes mellitus occurs in 10-40% of kidney transplant recipients and is associated with increased risk of developing cardiovascular diseases. Early identification of patients with a higher risk of developing diabetes could allow to take timely measures. However, no validated model exists to predict the risk of post-transplant diabetes mellitus., Methods: This retrospective study includes 267 adult patients who underwent kidney transplantation at the Antwerp University Hospital between January 2014 and August 2021. Post-transplant diabetes mellitus was diagnosed based on the American Diabetes Association definition at 3 months post-transplant. First, a logistic regression analysis was used to identify predictors for post-transplant diabetes mellitus. Second, criteria to identify patients with a high risk (> 35%) of developing post-transplant diabetes mellitus at 3 months were established., Results: At 3 months post-transplantation, 54 (20.2%) patients developed post-transplant diabetes mellitus. Univariable analysis showed that age, body mass index and HbA1c on the day of transplantation were associated with post-transplant diabetes mellitus. However, in a multivariable model with the same parameters, only HbA1c remained statistically significant. An absolute increase in HbA1c of 0.1% increases the odds for developing post-transplant diabetes mellitus by 28% (95% confidence interval 1.15-1.42). An HbA1c level ≥ 5.3% at transplantation, regardless of age or body mass index, is sufficient to identify patients with a post-transplant diabetes mellitus risk of ≥ 35% with a positive predictive value of 39% and a negative predictive value of 88%., Conclusions: The HbA1c value at transplantation was the strongest predictor for post-transplant diabetes mellitus at 3 months post-transplant. Furthermore, at least in our population, a pre-transplant HbA1c of ≥ 5.3% can be used as an easy tool to identify patients at high risk of early post-transplant diabetes mellitus., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Living donation challenges the ethical principle of non-maleficence in that it exposes healthy persons to risks for the benefit of someone else. This makes safety, informed consent (IC) and education a priority. Living kidney donation has multiple benefits for the potential donor, but there are also several known short- and long-term risks. Although complete standardization of IC is likely to be unattainable, studies have emphasized the need for a standardized IC process to enable equitable educational and decision-making prospects for the prevention of inequities across transplant centers. Based on the Three-Talk Model of shared decision-making by Elwyn et al., we propose a model, named 3-Step (S) Model, where each step coincides with the three ideal timings of the process leading the living donor to the decision to pursue living donation: prior to the need for kidney replacement therapy (team talk); at the local nephrology unit or transplant center, with transplant clinicians and surgeons prior to evaluations start (option talk); and throughout evaluation, after having learned about the different aspects of donation, especially if there are second thoughts or doubts (decision talk). Based on the 3-S Model, to deliver conceptual and practical guidance to nephrologists and transplant clinicians, we provide recommendations for standardization of the timing, content, modalities for communicating risks and assessment of understanding prior to donation. The 3-S Model successfully allows an integration between standardization and individualization of IC, enabling a person-centered approach to potential donors. Studies will assess the effectiveness of the 3-S Model in kidney transplant clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Phospholipase D3 (PLD3) polymorphisms are linked to late-onset Alzheimer's disease (LOAD). Being a lysosomal 5'-3' exonuclease, its neuronal substrates remained unknown as well as how a defective lysosomal nucleotide catabolism connects to AD-proteinopathy. We identified mitochondrial DNA (mtDNA) as a major physiological substrate and show its manifest build-up in lysosomes of PLD3-defective cells. mtDNA accretion creates a degradative (proteolytic) bottleneck that presents at the ultrastructural level as a marked abundance of multilamellar bodies, often containing mitochondrial remnants, which correlates with increased PINK1-dependent mitophagy. Lysosomal leakage of mtDNA to the cytosol activates cGAS-STING signaling that upregulates autophagy and induces amyloid precursor C-terminal fragment (APP-CTF) and cholesterol accumulation. STING inhibition largely normalizes APP-CTF levels, whereas an APP knockout in PLD3-deficient backgrounds lowers STING activation and normalizes cholesterol biosynthesis. Collectively, we demonstrate molecular cross-talks through feedforward loops between lysosomal nucleotide turnover, cGAS-STING and APP metabolism that, when dysregulated, result in neuronal endolysosomal demise as observed in LOAD., (© 2023. The Author(s).)

Tacrolimus (Tac) has a narrow therapeutic range. Dosing is generally targeted at Tac trough levels ( C 0 ), notwithstanding conflicting reports on the correlation between Tac C 0 and systemic exposure measured by the area-under-the-concentration-over-time curve (AUC). The Tac dose required to meet the target C 0 varies highly among patients. We hypothesized that patients requiring a relatively high Tac dose for a certain C 0 may show a higher AUC., Methods: We retrospectively analyzed data from 53 patients in which a 24-h Tac AUC 24 estimation was performed at our center. Patients were divided into those taking a low (≤0.15 mg/kg) or high (>0.15 mg/kg) once-daily Tac dose. Multiple linear regression models were used to investigate if the association between C 0 and AUC 24 changes according to dose level., Results: Despite the large difference in mean Tac dose between the low- and high-dose group (7 versus 17 mg/d), C 0 levels were similar. However, the mean AUC 24 was substantially higher in the high-dose group (320 ± 96 h·μg/L versus 255 ± 81 h·μg/L, P < 0.001). This difference remained significant after adjusting for age and race. For a same C 0 , every 0.01 mg/kg increase in Tac dose resulted in an AUC 24 increase of 3.59 h·μg/L., Conclusions: This study challenges the general belief that C 0 levels are sufficiently reliable to estimate systemic drug exposure. We demonstrated that patients requiring a relatively high Tac dose to attain therapeutic C 0 levels have higher drug exposure and could therefore potentially be overdosed., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Mass disasters are characterized by a disparity between health care demand and supply, which hampers complex therapies like kidney transplantation. Considering scarcity of publications on previous disasters, we reviewed transplantation practice during the recent COVID-19 pandemic, and dwelled upon this experience for guiding transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to save as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of health care resources., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: BK polyomavirus-associated nephropathy (PVAN) is a frequent complication in the early phase after kidney transplantation. The most important risk factor for PVAN is the intensity of immunosuppression. A recent study suggests that exposure to valganciclovir (VGC) could also be a risk factor., Methods: We performed a retrospective, single-center study to investigate the effect of valganciclovir exposure on the risk for PVAN during the first 100 days post transplant. Cytomegalovirus (CMV) seronegative recipients of a CMV seropositive donor kidney received VGC prophylaxis, whereas CMV seropositive recipients were managed by a pre-emptive CMV strategy. Cox regression analysis was used to identify risk factors for PVAN development with VGC treatment and strength of immunosuppressive therapy as time-dependent variables., Results: A total of 211 adults who received a kidney transplant between 2014 and 2019 were included. Eighteen (9%) developed PVAN. Multivariate regression analysis showed that women have a lower risk of developing PVAN (hazard ratio [HR] 0.08 (confidence interval [CI] 0.01-0.58), P = .013), whereas age was associated with an increased risk for PVAN (HR 1.04 for every additional year [CI 1.00-1.08], P = .029). There was a trend toward a lower risk of PVAN for patients on reduced immunosuppressive therapy (HR 0.44 [CI 0.15-1.24], P = .12). VGC use was not associated with the risk for PVAN (HR 0.99 [CI 0.35-2.78], P = .98)., Conclusions: In our study, VGC exposure was not associated with the risk for PVAN. Our study is the first to reassess in depth the hypothesis that VGC treatment increases the risk of PVAN. The unique strength of this study is the correction for the degree of immunosuppression and the statistical use of time-dependent covariates. This methodological approach can provide a foundation for further studies needed to confirm our findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Due to the shortage of deceased and genetically- or emotionally-related living donors, living unrelated paid donor (LURpD) kidney transplantation has been considered; however, this practice may result in medical, ethical and social dilemmas, induce organ trading (commodification), and even criminal activities. Commodification also risks undermining public trust in the transplant system and impeding the development of proper altruistic or deceased donor programs by ignoring altruism, volunteerism, and dignity. However, despite many objections by authoritative organizations, black market practices are involved in up to 10% of all transplants worldwide. The authors strongly discourage any payment or rewards for organ donation, and instead urge the governments of all countries to provide adequate and accessible kidney health care. However, it is an undeniable fact that paid-living donor transplantation is increasing despite all objections, disapprovals and regulations. We feel it as our responsibility not to ignore this uncertain and undesirable practice, but rather to underline the necessity for strict rules and prohibitions to minimize unacceptable medical, social and ethical risks as long as it exists. Furthermore, economic profit, be it direct or indirect, must not be the goal of those involved, and the employment of intermediaries must be avoided entirely. Additionally, the donor should be in a position where not donating has no detrimental effect on his/her future in any way (free agency). In our view, every country has the obligation and responsibility to provide adequate kidney health care and to make kidney transplantation accessible to those in need. This provision is key to stop transplant tourism and commercialization of kidney transplantation. The nephrology community has a duty to establish structures that optimize organ availability within strict ethical limits. The legal position of LURpD varies considerably worldwide. Strictly respecting each country's legislation and local values is mandatory to minimize medical and ethical risks and controversies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: SARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated., Methods: In the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16-21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose., Results: Overall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed., Conclusion: The current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Omicron variant, which has become the dominant strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, brings new challenges to preventing and controlling the infection. Moreover, the widespread implementation of vaccination policies before and after transplantation, and the development of new prophylactic and treatment strategies for coronavirus disease 2019 (COVID-19) over the past 12-18 months, has raised several new issues concerning kidney transplant recipients. In this special report, the ERA DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) Working Group addresses several questions related to everyday clinical practice concerning kidney transplant recipients and to the assessment of deceased and live kidney donors: what is the current risk of severe disease and of breakthrough infection, the optimal management of immunosuppression in kidney transplant recipients with COVID-19, the role of passive immunization and the efficacy of antiviral drugs in ambulatory patients, the management of drug-to-drug interactions, safety criteria for the use of SARS-CoV-2-positive donors, issues related to the use of T cell depleting agents as induction treatment, and current recommendations for shielding practices., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry provides complete population data on kidney disease epidemiology in the region of Flanders (Belgium), as it captures all native kidney biopsies performed in its population of 6.5 million inhabitants., Methods: From 2017 until 2019, 2054 adult kidney biopsies were included from 26 nephrology centers (one biopsy per patient). Data on nephrotic and nephritic syndrome were available in 1992 and 2026 biopsies, respectively. In a subgroup of 898 biopsies containing ≥10 glomeruli from 2018 to 2019, disease chronicity was graded using the Mayo Clinic Chronicity Score (MCCS). The association between clinical variables and MCCS was determined using simple and multiple linear regression models., Results: Nephrotic syndrome (present in 378 patients, 19.0%) was most frequently caused by minimal change disease in younger patients (18-44 years), membranous nephropathy in older patients (45-74 years) and amyloidosis in the elderly (>75 years). Nephritic syndrome (present in 421 patients, 20.8%) was most frequently caused by immunoglobulin A nephropathy (IgAN) in younger patients (18-64 years) and ANCA-associated vasculitis (AAV) in older patients (>64 years). AAV and IgAN were the most frequent underlying diagnoses in biopsies in which crescents were identified. In multivariable analysis, acute and chronic kidney disease and diagnoses of diabetic kidney disease, nephrosclerosis and hyperoxaluria/hypercalcemic nephropathy were associated with the highest MCCS increases., Conclusions: The FCGG registry validates data from previous Western European registries and provides a snapshot of disease chronicity in the whole biopsied Flemish population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Calcineurin inhibitors (CNIs) are the mainstay immunosuppressive therapy after kidney transplantation, despite their side effects. Recently, several randomized controlled trials attempting CNI withdrawal or minimization in stable, low-risk kidney transplant recipients led to an unacceptable risk of acute rejection and de novo HLA antibody formation. In the opinions of many, these trials definitively demonstrated that CNI-free regimens in the context of mycophenolate mofetil (MMF) maintenance are too risky. It can be argued, however, that the investigators failed to optimize the dose of the remaining immunosuppressive therapy. In particular, the potential benefit of MMF dosing based on the targeted mycophenolic acid (MPA) concentration was not taken into account. In this review, we present an overview of the studies on CNI withdrawal, both recent and older, paying specific attention to the MMF dose and elaborating on the possible benefit of MPA monitoring in this setting., (© 2021. Italian Society of Nephrology.)

Background: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients., Methods: A systematic literature review was performed using PubMed, Web of Science and the Cochrane Library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated., Results: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 {44.3% [95% confidence interval (CI) 34.1-54.7]} as compared with patients vaccinated with two doses of mRNA-1273 [58.4% (95% CI 47.2-69.2)]. The relative seroconversion rate was 0.795 (95% CI 0.732-0.864)., Conclusions: This systematic review and meta-analysis indicates that in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared with BNT162b2., Competing Interests: P.V.D. reported the University of Antwerp received research grants from GSK Biologicals, Pfizer, Sanofi, Merck, Themis, Osivax, Johnson & Johnson, Abbott, the Bill and Melinda Gates Foundation, PATH, the Flemish government and European Union outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Cytomegalovirus (CMV)-related complications after kidney transplantation remain a substantial challenge. Rather than applying one preventive strategy to all at-risk patients, we can now adapt our strategy at the individual patient level. Antiviral prophylaxis or a strict pre-emptive strategy may be optimal for patients at the highest risk for CMV, while patients at lower risk may benefit particularly from pre-emptive monitoring and the administration of therapy only if needed. CMV-specific T-cell assays may be useful for further refining the pre-transplant determination of CMV risk, and for guiding decisions about antiviral therapy need or duration. An immunosuppressive regimen including a mammalian target of rapamycin inhibitor reduces CMV risk and may thus be an attractive option in some patients. New antiviral agents may further expand our therapeutic arsenal in the near future, and the prospects of CMV vaccination and adoptive T-cell therapy appear to be on the horizon., (© The Author(s) 2020. Published by Oxford University Press on behalf of the ERA-EDTA.)

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders., Methods: From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included. A 'double diagnostic coding' strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses were reported and compared with other European registries., Results: The median age at biopsy was 61.1 years (interquartile range, 46.1-71.7); male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. Immunoglobulin A nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems., Conclusions: The FCGG registry, with its 'double diagnostic coding' strategy, provides useful population-based epidemiological data on a large Western European population and allows subgroup selection for future research., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Since patient survival after kidney transplantation is significantly improved with a shorter time on dialysis, it is recommended to start the transplant workup in a timely fashion., Methods: This retrospective study analyses the chronology of actions taken during the care for patients with chronic kidney disease (CKD) stage 5 who were waitlisted for a first kidney transplant at the Antwerp University Hospital between 2016 and 2019. We aimed to identify risk factors for a delayed start of the transplant workup (i.e. after dialysis initiation) and factors that prolong its duration., Results: Of the 161 patients included, only 43% started the transplant workup before starting dialysis. We identified the number of hospitalization days {odds ratio [OR] 0.79 [95% confidence interval (CI) 0.69-0.89]; P < 0.001}, language barriers [OR 0.20 (95% CI 0.06-0.61); P = 0.005] and a shorter nephrology follow-up before CKD stage 5 [OR 0.99 (95% CI 1.0-0.98); P = 0.034] as factors having a significant negative impact on the probability of starting the transplant screening before dialysis. The workup took a median of 8.6 months (interquartile range 5-14) to complete. The number of hospitalization days significantly prolonged its duration., Conclusion: The transplant workup was often started too late and the time needed to complete it was surprisingly long. By starting the transplant workup in a timely fashion and reducing the time spent on the screening examinations, we should be able to register patients on the waiting list before or at least at the start of dialysis. We believe that such an internal audit could be of value for every transplant centre., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

The clinical practice guideline Management of Obesity in Kidney Transplant Candidates and Recipients was developed to guide decision-making in caring for people with end-stage kidney disease (ESKD) living with obesity. The document considers the challenges in defining obesity, weighs interventions for treating obesity in kidney transplant candidates as well as recipients and reflects on the impact of obesity on the likelihood of wait-listing as well as its effect on transplant outcomes. It was designed to inform management decisions related to this topic and provide the backdrop for shared decision-making. This guideline was developed by the European Renal Association's Developing Education Science and Care for Renal Transplantation in European States working group. The group was supplemented with selected methodologists to supervise the project and provide methodological expertise in guideline development throughout the process. The guideline targets any healthcare professional treating or caring for people with ESKD being considered for kidney transplantation or having received a donor kidney. This includes nephrologists, transplant physicians, transplant surgeons, general practitioners, dialysis and transplant nurses. Development of this guideline followed an explicit process of evidence review. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and areas of future research are presented., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Kidney transplant recipients (KTRs) have increased incidence of de novo cancers. After having undergone treatment for cancer with curative intent, reducing the overall immunosuppressive load and/or switching to an alternative drug regimen may potentially be of great benefit to avoid cancer recurrence, but should be balanced against the risks of rejection and/or severe adverse events. The TLJ (Transplant Learning Journey) project is an initiative from the European Society for Organ Transplantation (ESOT). This article reports a systematic literature search undertaken by TLJ Workstream 3 to answer the questions: (1) Should we decrease the overall anti-rejection therapy in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer)? (2) Should we switch to mammalian target of rapamycin inhibitors (mTORi) in potentially cured post-kidney transplant cancer (excluding non-melanoma skin cancer)? The literature search revealed insufficient solid data on which to base recommendations, so this review additionally presents an extensive overview of the indirect evidence on the benefits versus risks of alterations in immunosuppressive medication. We hope this summary will help transplant physicians advise KTRs on how best to continue with anti-rejection therapy after receiving cancer treatment with curative intent, and aid shared decision-making, ensuring that patient preferences are taken into account., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Introduction: Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited reports. The aim of this study was to evaluate, in a large cohort of patients with long follow-up, the risk of recurrence of anti-GBM disease, the risk factors associated with clinical recurrence, and the long-term patient and graft survival., Methods: This was a multicenter retrospective study. Inclusion criteria were patients with anti-GBM glomerulonephritis who underwent transplantation of a kidney between 1977 and 2015. Exclusion criteria were systemic vasculitis, lupus erythematosus, and cryoglobulinemia. Recurrence was defined as reappearance of clinical signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies., Results: A total of 53 patients were included. Recurrence of anti-GBM glomerulonephritis in a first kidney transplant occurred in only 1 patient 5 years after transplantation (a prevalence rate of 1.9%) in the context of cessation of immunosuppressive drugs, and resulted in graft loss due to recurrence. Linear IgG staining on kidney biopsy in the absence of histological signs of proliferative glomerulonephritis was observed in 4 patients, in the context of cellular rejection. Patient survival was 100%, 94%, and 89% at 5, 10, and 15 years, respectively. Death-censored first-graft survival rates were 88%, 83%, and 79% at 5, 10, and 15 years, respectively., Conclusion: The recurrence rate of anti-GBM glomerulonephritis after transplantation is very low but is associated with graft loss. The long-term patient and graft survival rates are excellent., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis., Methods: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease., Results: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups., Conclusions: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA., Methods: From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodies detected in Luminex assays and the outcome of flowcytometric/complement-dependent cytotoxicity (CDC) crossmatches., Results: In patients with isolated pretransplant HLA-DP antibodies (N = 13), 6 experienced antibody-mediated rejection (AMR) and 3 patients lost their graft. In HLAMatchmaker analysis of HLA-DP mismatches (N = 72), HLA-DP DSA developed after cessation of immunosuppression in all cases with 84DEAV (N = 14), in 86% of cases with 85GPM (N = 6/7), in 50% of cases with 56E (N = 6/12) and in 40% of cases with 56A mismatch (N = 2/5). Correlation analysis between isolated HLA-DP DSA MFI and crossmatches (N = 90) showed negative crossmatch results with HLA-DP DSA MFI <2000 (N = 14). Below an MFI of 10,000 CDC crossmatches were also negative (N = 33). Above these MFI values both positive (N = 35) and negative (N = 16) crossmatch results were generated., Conclusions: Isolated HLA-DP DSA are rare, yet constitute a significant risk for AMR. We identified high-risk eplet mismatches that can lead to HLA-DP DSA formation. We therefore recommend HLA-DP typing to perform HLA-DP DSA analysis before transplantation. HLA-DP DSA with high MFI were not always correlated with positive crossmatch results., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for high-risk CMV-seronegative recipients with a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned., Methods: We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R- patients received valganciclovir (VGC) prophylaxis for 200 days, and R + patients were treated pre-emptively according to CMV DNAemia. Patients were followed until 1-year post-transplant., Results: Between April 2014 and March 2018, 40 D+/R- and 92 R + patients underwent kidney transplantation. Forty-six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200 days), but 15% developed post-prophylaxis or late-onset disease. Fifty-three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony-stimulating factor (5%). In the R + group, 40% received antiviral therapy for a median duration of 21 days; 5% developed early-onset CMV disease. Only 5% developed neutropenia. D+/R + status (hazard ratio (HR) 2.09,P = .004) and ATG use (HR 2.81, P < .0001) were risk factors for CMV reactivation., Conclusions: Prophylaxis leads to acceptable CMV control in high-risk patients but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk of CMV., (© 2020 Wiley Periodicals LLC.)

Background: Delayed graft function (DGF) remains a clinically relevant problem in the post-transplant period, especially in patients with a renal graft from a "donation after cardiac death" (DCD) donor. Controversy exists around the optimal perioperative fluid therapy in such patients. These patients may benefit from a perioperative saline loading fluid protocol, which may reduce the risk of DGF., Methods: We compared 2 cohorts of patients who underwent a renal transplantation with a graft from a DCD donor. From January 2003 until December 2012, patients (N = 46) were hemodynamically managed at the discretion of the care-giving physician, without a preoperative fluid administration protocol (first study period). From January 2015 until March 2019 (N = 26), patients received saline loading before, during, and after kidney transplantation according to a well-defined saline loading fluid protocol (second study period). The relationship between the use of this perioperative fluid protocol and DGF was analyzed using univariable and multivariable logistic regression models., Results: DGF occurred in 11 of 46 (24%) patients in the first study period and in 1 of 26 (4%) in the second study period (P < .05). In a multivariable model, correcting for cold ischemia time and Kidney Donor Risk Index, the use of a saline loading fluid protocol in the perioperative phase was nearly significantly associated with a decrease in DGF (P = .07)., Conclusion: In our DCD transplant population, DGF rates were low. Our data further strongly suggest that implementation of a perioperative saline loading fluid protocol was independently associated with a lower risk of DGF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A systematic review and meta-analysis were performed to investigate the value of donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker in diagnosing kidney allograft rejection. We searched PubMed, Web of Science and the Cochrane Library for original research papers published between January 1994 and May 2020 on dd-cfDNA fractions in blood of kidney allograft recipients. A single-group meta-analysis was performed by computing pooled estimates for dd-cfDNA fractions using the weighted median of medians or quantile estimation (QE) approach. Weighted median differences in medians (WMDMs) and median differences based on the QE method were used for pairwise comparisons. Despite heterogeneity among the selected studies, the meta-analysis revealed significantly higher median dd-cfDNA fractions in patients with antibody-mediated rejection (ABMR) than patients without rejection or patients with stable graft function. When comparing patients with T cell-mediated rejection (TCMR) and patients with ABMR, our two statistical approaches revealed conflicting results. Patients with TCMR did not have different median dd-cfDNA fractions than patients without rejection or patients with stable graft function. dd-cfDNA may be a useful marker for ABMR, but probably not for TCMR., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Hemodialysis-related portosystemic encephalopathy (HRPSE) is a clinical phenomenon where portosystemic encephalopathy (PSE) develops without liver dysfunction, usually caused by changes in the portosystemic blood flow related to hemodialysis. We describe the case of a 22-year old patient with a transjugular intrahepatic portosystemic shunt (TIPS) who developed HRPSE several months after initiation of hemodialysis. Despite initial therapy with laxatives and neomycin symptoms recurred. It was only after relocation of the hemodialysis catheter from the superior caval vein to the femoral vein that symptoms completely resolved.

Purpose of Review: The kidney transplantation landscape has changed dramatically over the last 2 decades. First, transplantation is performed in patients previously considered ineligible for transplantation, including older patients and patients with multiple comorbidities. Second, organ shortages have increased the use of less-than-optimal donor kidneys, like organs from expanded criteria donors or donors after cardiac death. Third, improvements in managing chronic kidney disease and dialysis have improved survival on dialysis. Therefore, the question arises: does transplantation currently benefit older transplant candidates?, Recent Findings: The current review describes important changes in transplantation over the last 20 years. We review recent data on survival with dialysis versus transplantation in older individuals. Finally, we consider methodological issues that might influence conclusions drawn in current studies., Summary: Limited data are available to assess the potential survival benefit of kidney transplantations in older individuals. The available evidence suggests that transplantation might provide survival benefit in older individuals, even with aged kidney donors, but risks vary widely with donor quality and recipient health status. More research is needed to make adequate predictions of which donor kidneys might lead to good outcomes and which patient characteristics might define a good transplant candidate.

Background: The Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate., Methods: From April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers., Results: After implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney., Conclusions: Implementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.)

Aim: To compare the performance of 3 published delayed graft function (DGF) calculators that compute the theoretical risk of DGF for each patient., Methods: This single-center, retrospective study included 247 consecutive kidney transplants from a deceased donor. These kidney transplantations were performed at our institution between January 2003 and December 2012. We compared the occurrence of observed DGF in our cohort with the predicted DGF according to three different published calculators. The accuracy of the calculators was evaluated by means of the c-index (receiver operating characteristic curve)., Results: DGF occurred in 15.3% of the transplants under study. The c index of the Irish calculator provided an area under the curve (AUC) of 0.69 indicating an acceptable level of prediction, in contrast to the poor performance of the Jeldres nomogram (AUC = 0.54) and the Chapal nomogram (AUC = 0.51). With the Irish algorithm the predicted DGF risk and the observed DGF probabilities were close. The mean calculated DGF risk was significantly different between DGF-positive and DGF-negative subjects ( P < 0.0001). However, at the level of the individual patient the calculated risk of DGF overlapped very widely with ranges from 10% to 51% for recipients with DGF and from 4% to 56% for those without DGF. The sensitivity, specificity and positive predictive value of a calculated DGF risk ≥ 30% with the Irish nomogram were 32%, 91% and 38%., Conclusion: Predictive models for DGF after kidney transplantation are performant in the population in which they were derived, but less so in external validations., Competing Interests: Conflict-of-interest statement: This project was an investigator driven study without any support from external organizations. The authors have no conflict of interest.

Data from the nineties showed that even older individuals had a survival advantage with kidney transplantation compared to dialysis. Consequently, we are increasingly wait-listing high-risk patients in terms of age and co-morbidities. However, times are changing. Due to severe organ shortage we now use more often expanded criteria donor kidneys with less favorable outcomes, while at the same time survival on dialysis is improving. The question therefore rises again if elderly patients really benefit from transplantation nowadays. At least for the U.S., recent data still suggest an overall survival benefit with transplantation in older recipients but the risks vary greatly with the health status of the recipient and with the type of donor. Especially for transplant centers outside of the U.S., recent large studies are lacking. Because of continuing changes in both donor and recipient characteristics as well as dialysis outcomes, a permanent area-specific reassessment of data is needed. In this review we describe the important evolutions in transplant and dialysis care over the last 20 years and provide an overview on recent data comparing survival on dialysis versus transplantation in the elderly., (Copyright © 2015 Elsevier Inc. All rights reserved.)