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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment‐related side effects and improve long‐term outcomes of kidney transplantation. The CISTCERT study compared the efficacy and safety of these two strategies. In this multicenter, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA), and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). 5‐year patient survival (89% vs. 86%; P = NS) and death‐censored graft survival (95% vs. 96%; P = NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm, respectively. 51CrEDTA clearance was comparable in the intention‐to‐treat analysis, but in the on‐treatment population, the EVL/MPA/steroids arm exhibited a superior 51CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs. 52.4, P = 0.05 and 59.1 vs. 46.2ml/min/1.73 m2, P = 0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of posttransplant diabetes (26% vs. 6%, P = 0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. Both regimens provide an excellent long‐term patient survival and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection. (ClinicalTrials.gov number: NCT00903188; EudraCT Number 2007‐005844‐26). [ABSTRACT FROM AUTHOR]

Introduction: A growing number of patients started renal replacement therapy (RRT) in Western industrialized countries between 1980 an early 2000s. Thereafter reports from national and international registries suggest a trend towards stabilization and sometimes a decrease in the incidence rate. Aim: To investigate the differences in overall and age-specific incidence rates between industrialized countries from 1998 until 2013. Secondly, to investigate changes in incidence rates over time and their association with specific age categories. Method: We extracted the unadjusted overall incidence of RRT and age-specific incidence rates from renal registry reports in Europe, the United States, Canada, Australia and New Zealand. Time trends in the incidence rate by country and age categories were analyzed by Joinpoint regression analysis. Results: The incidence rate in 2013 ranged from 89 per million population (pmp) in Finland to 363 pmp in the US. Incidence rates in the lower age categories (20–64 year) were similar between countries and remained stable over time. Higher incidence countries were characterized by higher numbers of patients in both the 65–74 and ≥75 year categories starting RRT. Joinpoint analysis confirmed that most countries had significant reductions in the incidence rate at the end of the study period. These reductions were explained by lower numbers of older patients starting RRT and were observed also in countries with lower overall incidence rates. Conclusion: This study confirmed different incidence rates of RRT between industrialized countries worldwide. Countries with the highest overall incidence rates also had the highest incidence rates in the oldest age categories. Since the early 2000's the number of older patients starting RRT is either stabilizing or even decreasing in most countries. This reduction is universal and is also observed in countries with previously low incidence rates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This position statement brings up guidance on pre-emptive kidney transplantation from living donors. The provided guidance is based on a systematic review of the literature. [ABSTRACT FROM AUTHOR]

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines. The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/ gft218 and can be downloaded freely from http://www. oxfordjournals.org/our_journals/ndt/era_edta.html. [ABSTRACT FROM AUTHOR]

The allocation of deceased donor kidneys has become more complex because of the increasing spectrum of donors and recipients age and comorbidities. Several scoring systems have been proposed to evaluate the donor quality of deceased donor kidneys, based on clinical, pathological or combined parameters to predict the risk of renal allograft failure. Nonetheless, besides the dichotomous extended criteria donor (ECD) score, none of the others have been used in clinical practice because of numerous reasons, ranging from lack of robust validation to the technical challenges associated with the evaluation of donor biopsies. Recently, the Kidney Donor Risk Index (KDRI) and Profile Index (KDPI) were introduced in the USA as a refined version of the ECD score. This scoring system is based on 10 donor factors, therefore providing a finely granulated evaluation of donor quality without the need of a kidney biopsy. Here, we review the advantages and drawbacks of the main scoring systems, and we describe the components of the KDRI and KDPI. It is an easily accessible online tool, based solely on donor factors readily available at the moment of the donor offer. Importantly, the KDPI has also been made part of the longevity matching' allocation in the USA, where the best kidneys are allocated to the recipients with the longest predicted post-transplant survival. The KDRI should provide us with a robust qualitative evaluation of deceased donor quality, and therefore will probably play a role in deceased donor kidney allocation policies across Europe in the near future. Hopefully, the KDRI and the KDPI should help transplant programmes to better allocate the scarce resource of deceased donor kidneys. [ABSTRACT FROM AUTHOR]

KDIGO (Kidney Disease: Improving Global Outcomes) is an international independent body aiming to ‘improve the care and outcomes of kidney disease patients worldwide, through the development and implementation of clinical practice guidelines’. Recently, the KDIGO work group has produced comprehensive clinical practice guidelines for the care of kidney transplant recipients (KTRs). The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy and other complications that are common in KTRs, including haematological and bone disorders.Because most guidelines were ‘soft’ rather than ‘strong’, and because global guidelines need to be adapted and implemented into the regional context where they are used, the European Renal Best Practice (ERBP) Advisory Board appointed a work group of transplant nephrologists and surgeons to review the newest KDIGO guideline and comment on its relevance and applicability for European KTRs.In this article, we concentrate only on those guidelines which we considered worth amending or adapting. All guidelines not mentioned are fully endorsed. [ABSTRACT FROM AUTHOR]

The article offers information about the nephrology guidance landscape which was thoroughly changed with the coming of the Kidney Diseases Improving Global Outcome (KDIGO) initiative. It was originally perceived that KDIGO would cover the whole spectrum which produces new and updated nephrology guidelines on any theme considered suitable. An overview of the structure that will offer specific professional support is presented.

The article discusses the initiatives of a commission created by the Council of the European Renal Association-European Dialysis and Transplantation Association (ERA-EDTA) towards the development of a European nephrology guidance. The establishment of the commission was spurred by the inability of the Kidney Diseases Improving Global Outcome (KDIGO) initiative to cover all topics. It is expected that emphasis will be placed on the differences between guidance, recommendations and position statements.

Abramowicz D, Vanrenterghem Y, Squifflet J-P, Kuypers D, Mourad M, Meurisse M, Wissing M. Efficacy and cardiovascular safety of daclizumab, mycophenolate mofetil, tacrolimus, and early steroid withdrawal in renal transplant recipients: a multicenter, prospective, pilot trial. Clin Transplant 2005: 19: 475–482. © Blackwell Munksgaard, 2005 This single-arm, open-label, pilot study was designed to assess the efficacy and cardiovascular safety profile of daclizumab, a humanized monoclonal interleukin (IL)-2R α antibody, in combination with mycophenolate mofetil (MMF), tacrolimus, and early corticosteroid withdrawal in renal transplant recipients. Seventy-nine renal allograft recipients were treated with daclizumab (1 mg/kg; five doses starting on the day before transplant and then every two weeks), MMF (1 g b.i.d.), tacrolimus (0.2 mg/kg/d), and low-dose prednisolone, which was withdrawn at day 150 after transplant. The rate of acute rejection was determined at 12 months. Lipid profile, oral glucose tolerance, and adverse events were monitored. Of the 76 patients eligible for analysis, eight (10.5%) developed biopsy-proven acute rejection (BPAR). Ten (13.2%) experienced clinical and/or BPAR. Corticosteroids were withdrawn completely in 91% of patients at 12 months. Graft and patient survival were 97.5% and 98.7% respectively. Mean total cholesterol and triglycerides were significantly lower at 12 months post-transplant than at baseline (201 ± 47.5 vs. 190.8 ± 43.6 mg/dL, p = 0.005 and 196.2 ± 133.2 vs. 144.5 ± 76.8 mg/dL, p < 0.001, respectively). Mean hemoglobin A1c levels did not differ between baseline (5.54%) and 12 months (5.48%). New-onset post-transplant diabetes mellitus occurred in 6.6% of the non-diabetic transplanted patients. The proportion of patients with abnormal oral glucose tolerance test (OGTT) was 47% at 3 months and 39% at 12 months (p = NS). Daclizumab induction in combination with MMF, tacrolimus, and low-dose (followed by withdrawal) prednisolone appears to be effective and safe in patients receiving renal allografts. The regimen appears to be associated with a favorable cardiovascular profile. [ABSTRACT FROM AUTHOR]

Background: Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. Methods: Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. Results: Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. Conclusion: Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity. Key learning points: What was known - In high-risk groups such as kidney transplant patients and dialysis patients, the immune system does not function optimally due to several metabolic processes and lifelong use of immunosuppressants. - Severe infection with SARS-CoV-2 in these high-risk groups is known to be associated with a more serious course of the disease. - Severe disease after SARS-CoV-2 infection was rarely reported but all concerned KTRs who lacked immune responses after vaccination. - Antibody levels decreased four weeks post-vaccination, which emphasizes the importance of booster vaccines. - Kidney transplant recipients with prior COVID-19 exhibited higher anti-Spike IgG levels after a single dose of a SARS-CoV-2 mRNA-based vaccine. This study adds - Humoral immune response to SARS-CoV-2 in kidney transplant recipients was more robust following infection than vaccination. - Next to kidney transplant recipients, patients on dialysis with prior COVID-19 exhibited higher anti-RBD and anti-S1S2 IgG levels as well, so hybrid immunity seems the best possible defence against severe COVID-19 disease in both populations. - Kidney transplant recipients showed the highest IgA titres compared to any other group after double-dose vaccination and infection, along with the lowest IgG titres after vaccination. Potential impact - Our results strengthen the need to administer all the recommended vaccines to patients with end-stage renal disease, and to consider booster vaccination. - Our findings make an important contribution to the COVID-19 research field by analysing both IgG and IgA serology and neutralizing antibody capacity after infection and vaccination, leading to a better understanding of the quality of the humoral immune response and its relationship with clinical data. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 ± 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed ‘de novo’ high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003). [ABSTRACT FROM PUBLISHER]

In kidney failure, uraemic toxins and a sedentary lifestyle can induce insulin resistance, although patients may remain normoglycaemic because of a decreased appetite, reduced gluconeogenesis and impaired degradation of insulin [[1]]. Early post-transplant hyperglycaemia (EPTH) occurs in more than 75% of patients after kidney transplantation (KT), often evolving towards post-transplant diabetes mellitus (PTDM), defined as newly diagnosed diabetes >45 days after transplantation [[1]]. However, several protocol violations might have blurred the benefit of early basal insulin intervention: three patients did not receive insulin (although needed), insulin was not stopped in four patients despite normal glycaemia and one patient declined treatment. [Extracted from the article]

Presents a letter to the editor on the therapeutic use of peroxisome proliferator-activated receptors (PPARs) in renal disease. Indication that fibrates are bound to the active PPARs; Emphasis on the influence of fibrate on renal dysfunction; Development of an impairment of renal function during fibrate therapy.

The article presents a letter to the editor in response to an article in the January 15,1998 issue about renal transplantation.

Owing to the vulnerability of patients with chronic kidney disease to infectious diseases, the coronavirus disease 2019 (COVID-19) pandemic has been particularly devastating for the nephrology community. Unfortunately, the possibility of future COVID-19 waves or outbreaks of other infectious diseases with pandemic potential cannot be ruled out. The nephrology community made tremendous efforts to contain the consequences of the COVID-19 pandemic. Despite this, the COVID-19 pandemic has highlighted several shortcomings in our response to the pandemic and has taught us important lessons that can be utilized to improve our preparedness for any future health crises of a similar nature. In this article we draw lessons from the European Renal Association COVID-19 Database (ERACODA) project, a pan-European collaboration initiated in March 2020 to understand the prognosis of COVID-19 in patients on kidney function replacement therapy. We discuss the challenges faced in generating timely and robust evidence for informed management of patients with kidney disease and give recommendations for our preparedness for the next pandemic in Europe. Limited collaboration, the absence of common data architecture and the sub-optimal quality of available data posed challenges in our response to COVID-19. Aligning different research initiatives, strengthening electronic health records, and involving experts in study design and data analysis will be important in our response to the next pandemic. The European Renal Association may take a leading role in aligning research initiatives via its engagement with other scientific societies, national registries, administrators and researchers. [ABSTRACT FROM AUTHOR]

Mass disasters are characterized by a disparity between healthcare demand and supply, which hampers complex therapies like kidney transplantation. Considering the scarcity of publications on previous disasters, we reviewed transplantation practice during the recent coronavirus disease 2019 (COVID-19) pandemic, and dwelled upon this experience to guide 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 saving 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 healthcare resources. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The letter to the editor refers to an article by Dr. Lee about the absence of HBsAG in people whose HBV infection has healed but who still might be harboring HBV DNA in the liver.

A letter to the editor is presented in response to an article related to HLA compatibility and graft survival after heart transplantation in the March 24, 1994 issue.

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. [ABSTRACT FROM AUTHOR]

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors. [ABSTRACT FROM AUTHOR]

Background. FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine.Methods. This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation.Results. Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm.Conclusion. FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients. [ABSTRACT FROM AUTHOR]

Several desensitization strategies have been investigated for the reversal of acute antibody-mediated rejection or for the removal of preformed anti-HLA antibodies, with the aim to promote access to renal transplantation. Today, their success appears limited or incomplete. Bortezomib, a selective inhibitor of the 26S proteasome, which is largely used in the treatment of multiple myeloma, could be a novel promising desensitizing agent. Its mechanism of action and preliminary clinical use in renal transplantation is reviewed here. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB. We performed this multicentre, randomized, open-label trial in kidney transplant recipients who had ASB and were ≥2 months post-transplantation. We randomly assigned participants to receive antibiotics or no therapy. The primary outcome was the incidence of symptomatic UTI over the subsequent 12 months. One hundred and ninety-nine kidney transplant recipients with ASB were randomly assigned to antibiotics (100 participants) or no therapy (99 participants). There was no significant difference in the occurrence of symptomatic UTI between the antibiotic and no-therapy groups (27%, 27/100 versus 31%, 31/99; univariate Cox model: hazard ratio 0.83, 95%CI: 0.50–1.40; log-rank test: p 0.49). Over the 1-year study period, antibiotic use was five times higher in the antibiotic group than in the no-therapy group (30 antibiotic days/participant, interquartile range 20–41, versus 6, interquartile range 0–15, p < 0.001). Overall, 155/199 participants (78%) had at least one further episode of bacteriuria during the follow-up. Compared with the participant's baseline episode of ASB, the second episode of bacteriuria was more frequently caused by bacteria resistant to clinically relevant antibiotics (ciprofloxacin, cotrimoxazole, third-generation cephalosporin) in the antibiotic group than in the no-therapy group (18%, 13/72 versus 4%, 3/83, p 0.003). Applying a screen-and-treat strategy for ASB does not reduce the occurrence of symptomatic UTI in kidney transplant recipients who are more than 2 months post-transplantation. Furthermore, this strategy increases antibiotic use and promotes the emergence of resistant organisms. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • The lack of adequate early graft perfusion after a kidney transplantation may contribute to the pathogenesis of delayed graft function (DGF). • DGF rate in donation after circulatory death (DCD) transplantation decreased from 24% to 4% in our center after implementation of a new perioperative hemodynamic strategy: "a saline loading fluid protocol." • Together with maintaining a short cold ischemia time and delayed introduction of calcineurin inhibitors, the use of this saline loading fluid protocol may contribute to a low risk of DGF in recipients of DCD kidneys. [ABSTRACT FROM AUTHOR]

Background: During routine post-kidney transplant care, most European transplant physicians screen patients for asymptomatic bacteriuria. The usefulness of this strategy is debated. To make screening cost-effective, asymptomatic bacteriuria should be prevalent enough to justify the expense, and antibiotics should improve patient outcomes significantly if asymptomatic bacteriuria is detected. Regrettably, the prevalence of asymptomatic bacteriuria among kidney transplant recipients is not well defined. Methods: To determine the prevalence of asymptomatic bacteriuria among kidney transplant recipients, we did a cross-sectional study among kidney transplant recipients undergoing routine surveillance in three outpatient transplant clinics in Belgium and France. We excluded patients who were in the first two months post-transplantation and/or had a urinary catheter. Asymptomatic participants who had a urine culture with one organism isolated at ≥ 105 CFU/mL were asked to provide a confirmatory urine specimen. Asymptomatic bacteriuria was defined per Infectious Diseases Society of America guidelines. Results: We screened 500 consecutive kidney transplant recipients. Overall, the prevalence of asymptomatic bacteriuria was 3.4% (17/500 patients). It was similarly low among kidney transplant recipients who were between 2 and 12 months after transplantation (1.3%, 1/76 patients) and those who were farther after transplantation (3.8%, 16/424 patients: p = 0.49). Asymptomatic bacteriuria was significantly associated with female gender (risk ratio 3.7, 95% CI 1.3–10.3, p = 0.007) and older age (mean age: 61 ± 12 years [bacteriuric participants], versus 53 ± 15 years [non-bacteriuric participants], p = 0.03). One participant’s colistin-resistant Escherichia coli isolate carried the globally disseminated mcr-1 gene. Conclusions: Among kidney transplant recipients who are beyond the second month post-transplant, the prevalence of asymptomatic bacteriuria is low. Further studies are needed to ascertain the cost-effectiveness of a screen-and-treat strategy for asymptomatic bacteriuria in this population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mesenchymal-epithelial transition (MET) exon 14 skipping mutations occur in ~3% of patients with non-small-cell lung cancer (NSCLC), the latter accounting for 85% of all lung cancers [[1]]. Meanwhile, physicians should be aware of the possible side effect of MET inhibitors causing pseudo-AKI and use non-creatinine-based methods to distinguish a true AKI from pseudo-AKI. If one wants to study the possible inhibitory effect of tepotinib on tubular creatinine secretion via OAT2 I in vitro i , the OAT2-mediated uptake of creatinine on OAT2-overexpressing cell cultures in the absence versus presence of tepotinib could be evaluated. [Extracted from the article]

Background Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions. Methods We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012–June 2015). Whole-genome sequencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected. Results We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences were apparent for 86 other bacterial and host variables. Conclusions Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied. [ABSTRACT FROM AUTHOR]