Effect of education on sun-safe behaviour in kidney transplant recipients.

BACKGROUND: Organ transplant recipients (OTR) are more likely to develop skin cancer than the general population. One of the main components of the exposome that triggers the development of skin tumours is solar ultraviolet (UV) radiation. To reduce the incidence of harmful consequences of sun exposure, sun protection education is needed for patients taking long-term immunosuppressive drugs. METHODS: In a previous study, we assessed the sun-safe behaviour of 221 OTR using a questionnaire before and after transplantation and personally educated the patients about proper sun protection. After the education, there were no further reminder presentations. Presently, the sun protection and sun seeking habits of the available 176 of these patients were questioned to assess the long-term effect of the previous sun protection education. RESULTS: Two-four years after the education, more patients wore hats and protected their skin with long-sleeved clothing than before the education. In terms of sun seeking habits, both occupational and recreational sun exposure decreased significantly. Significantly fewer people went on holiday after transplantation, but those who went on holiday spent significantly less time in the sun. CONCLUSION: The long-term positive effects of education can be seen both in the patients' sun protection and in their sun seeking habits. However, the long-term goal is to maintain these results and thereby reduce the likelihood of skin tumours and consequently the associated tumour death.

Post-Transplant Fecal Carriage of Antibiotic Resistant and B-Lactamases-Producing Enterobacteriales among Renal Transplant Recipients.

BACKGROUND: The intestinal colonization and transmission of antibiotic-resistant Enterobacteriales to renal transplant recipients may pose a threat to them because they are profoundly immunocompromised and vulnerable to infection. Hence, it is crucial to identify these antibiotic-resistant fecal Enterobacteriales harboring high-risk populations. The objective of this study was to determine antibiotic resistance as well as ß-lactamases production in fecal Enterobacteriales among renal transplant recipients. METHODS: The stool samples, one collected from each transplant recipient, were processed for isolation and identification of Enterobacteriales and were tested for their antibiotic susceptibility, extended-spectrum ß-lactamase, and metallo-ß-lactamase production by standard methods. RESULTS: A total of 103 Enterobacteriales comprising of Escherichia coli (86.4%), Klebsiella species (11.7%), and Citrobacter species (1.9%) were isolated and more than 60% of the E. coli were found resistant to ceftazidime and ciprofloxacin and around half of the Klebsiella species were resistant to ceftazidime and fluroquinolones. The extended-spectrum ß-lactamase production was seen in 3.4% and 8.3% and metallo-ß-lactamase production in 24.7% and 33.3% of E. coli and Klebsiella species, respectively. The high proportion of ß-lactamase-producers were resistant to piperacillin-tazobactam, meropenem, gentamicin, and amikacin than ß-lactamases non-producers. CONCLUSION: Since the antibiotic resistance is higher in fecal Enterobacteriales, each renal transplant recipient should be screened for these highly resistant intestinal colonizers after transplantation in order to prevent infections and to reduce the rate of transplant failure due to infections.

Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

Predicting Cellular Rejection of Renal Allograft Based on the Serum Proteomic Fingerprint.

Kidney transplantation is an essential medical procedure that significantly enhances the survival rates and quality of life for patients with end-stage kidney disease. However, despite advancements in immunosuppressive therapies, allograft rejection remains a leading cause of organ loss. Notably, predictions of cellular rejection processes primarily rely on biopsy analysis, which is not routinely performed due to its invasive nature. The present work evaluates if the serum proteomic fingerprint, as acquired by Fourier Transform Infrared (FTIR) spectroscopy, can predict cellular rejection processes. We analyzed 28 serum samples, corresponding to 17 without cellular rejection processes and 11 associated with cellular rejection processes, as based on biopsy analyses. The leave-one-out-cross validation procedure of a Naïve Bayes model enabled the prediction of cellular rejection processes with high sensitivity and specificity (AUC > 0.984). The serum proteomic profile was obtained in a high-throughput mode and based on a simple, rapid, and economical procedure, making it suitable for routine analyses and large-scale studies. Consequently, the current method presents a high potential to predict cellular rejection processes translatable to clinical scenarios, and that should continue to be explored.

Long-term outcomes of two-dose alemtuzumab induction in pediatric kidney transplantation.

BACKGROUND: Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long-term information on its use in pediatric recipients remains sparse. METHODS: We performed a single-center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post-transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia. RESULTS: Median follow-up time was 7.9 years (IQR 5-13.6 years). Median graft survival was 16.5 years (95% CI 11.6-unknown). DSA developed in 36.5% at a median of 944 days (IQR 252-2113 days). Incidences of BK polyomavirus DNAemia (BKPyV-DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post-transplant. Median duration of lymphopenia was 365 days (IQR 168-713 days); 19.3% of patients remained lymphopenic at 3 years post-transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia. CONCLUSIONS: A two-dose alemtuzumab induction protocol can have excellent outcomes with a steroid-free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long-term outcomes.

Successful use of eculizumab in immediate ANCA vasculitis recurrence in a pediatric kidney transplant.

BACKGROUND: Kidney transplantation is an acceptable therapy end-stage kidney disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis with risk of disease recurrence ranging from 3% to 17%. Standard posttransplant immunosuppression is the mainstay of therapy after recurrence. Recently, new medications focused on complement regulation and avoidance of steroids have been shown to be effective in treating antineutrophil cytoplasmic antibody (ANCA) vasculitis with no studies in the pediatric population. METHODS: We report a 5-year-old patient with immediate recurrence of positive myeloperoxidase (MPO)-ANCA vasculitis after deceased donor kidney transplant and the novel use of eculizumab to salvage the graft. RESULTS: Eculizumab and transition to ravulizumab has been successful in improving graft function and maintenance of disease remission after immediate MPO-ANCA vasculitis recurrence posttransplant. CONCLUSIONS: Complement inhibitors may be used in addition to standard immunosuppression postkidney transplant in a pediatric patient with MPO-ANCA vasculitis recurrence without higher rates of infections.

The diagnostic significance of C4d deposits, as an immunohistochemical proof of complement activation, in kidney glomerular pathologies and kidney transplantation.

C4d, a split product of C4 activation in classical and lectin pathways of the complement system activation, has been regarded as a footprint of tissue damage in antibody-mediated rejection in transplantology. The introduction of C4d staining into daily clinical practice aroused an ever-increasing interest in the role of antibody-mediated mechanisms in kidney allograft rejection. However, this marker of complement activation is also important in other various kidney glomerular pathologies such as immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and others. In routine histopathological practice, C4d staining can be done by two histological methods, specifically by immunofluorescence on frozen tissue using monoclonal antibody to C4d (with the downside of unsteady availability of frozen tissue) or by immunohistochemistry using C4d antibodies on formalin-fixed and paraffin-embedded renal tissue. The aim of this narrative review is to summarize recent knowledge about the complement fragment C4d and its significance in different kidney pathologies, focusing on its immunohistochemical detection in renal tissue biopsies. We have supplemented this review with our experience with our proprietary methodology of preparation and practical use of antibodies such as anti-C4d, on a small national level. Immunohistochemical staining for C4d has revolutionized the field of renal histopathology. Despite being a simple diagnostic test, its utility can be of utmost importance, especially in a resource-poor setting where immunofluorescence and frozen tissue may not be available (Fig. 2, Ref. 53). Keywords: C4d deposition, immunohistochemistry, kidney glomerular diseases, kidney transplant, renal tubular damage.

Global prevalence of onychomycosis in general and special populations: An updated perspective.

BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.

AI-driven translations for kidney transplant equity in Hispanic populations.

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT's capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1-5 rubric. The inter-rater reliability of the evaluators, measured by Cohen's Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT's potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients.

Relationship between the microenvironment and survival in kidney transplantation: a bibliometric analysis from 2013 to 2023.

Background: Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation. Methods: Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package "bibliometrix". The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering. Results: Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor ß, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years. Conclusion: This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.

Effect of pre-emptive rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients: A case series from the pediatric nephrology research consortium.

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.

Kidney transplant in pediatric gut transplant recipients - Technical challenges and outcomes.

BACKGROUND: There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). METHODS: A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. RESULTS: 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. CONCLUSION: Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.

Factors associated with therapeutic non-adherence in renal transplant patients: a bicentric study in Algeria / Facteurs associés à la non-observance thérapeutique chez les patients greffés rénaux : une étude bicentrique en Algérie

Introduction: Medication non-adherence is a global concern, particularly in the context of renal transplantation, where it leads to graft failures, increased hospitalizations, diminished quality of life for patients, and higher healthcare costs. The aim of this study was to assess the level of therapeutic adherence among Algerian kidney transplant recipients and identify potential influencing factors. Methods: A descriptive, cross-sectional bicenter study was conducted among kidney transplant patients receiving outpatient care at two specialized medical centers in Algeria: the Urology Department of the Hospital Establishment for Urology, Nephrology, and Renal Transplantation in Constantine, and the Nephrology and Renal Transplantation Department of the University Hospital Center (CHU) in Blida, spanning from January to December 2022. Therapeutic adherence was assessed using the 8-item Morisky questionnaire, while the level of knowledge was analyzed through a 12-item questionnaire. Logistic regression was used to identify factors associated with non-adherence to therapy. Results: This study included 130 patients with an average age of 47 years and a sex ratio of 1.7. The results revealed therapeutic non-adherence in 40.8% of the patients. Multivariate analysis identified several potentially associated factors, including residence, unemployment status, lack of affiliation with a health insurance fund, the use of a therapeutic regimen involving triple therapy, the occurrence of adverse effects, limited education level, and insufficient disease knowledge. Furthermore, non-adherence was associated with an increased risk of graft rejection. Conclusion: The findings of this study highlight concerning therapeutic adherence among kidney transplant recipients, emphasizing the crucial importance of therapeutic education to improve treatment adherence and underscoring the need to integrate these factors into clinical patient management.

Introduction: La non-observance thérapeutique est un problème mondial préoccupant, notamment dans le contexte de la transplantation rénale où elle entraîne des échecs de greffe, une augmentation des hospitalisations, une détérioration de la qualité de vie des patients et des coûts de santé accrus. Cette étude avait pour objectif d'évaluer le niveau d'observance thérapeutique chez les transplantés rénaux algériens et d'identifier les facteurs qui pourraient l'influencer. Méthodes: Une étude descriptive transversale bicentrique a été menée auprès de patients transplantés rénaux suivis en ambulatoire dans deux centres médicaux spécialisés en Algérie : le service d'urologie de l'Établissement hospitalier spécialisé (EHS) en urologie, néphrologie et transplantation rénale de Constantine ainsi que le service de néphrologie et transplantation rénale du Centre hospitalier universitaire (CHU) de Blida, sur une période allant de janvier à décembre 2022. L'observance thérapeutique a été évaluée à l'aide du questionnaire à 8 items de Morisky, tandis que le niveau de connaissance a été analysé à travers un questionnaire de 12 items. La régression logistique a été utilisée pour identifier les facteurs associés à la non-observance thérapeutique. Résultats: Cette étude a inclus 130 patients présentant un âge moyen de 47 ans et un sex ratio de 1,7. Les résultats ont révélé une non-observance thérapeutique chez 40,8 % des patients. L'analyse multivariée a permis d'identifier plusieurs facteurs potentiellement associés à cette non-observance, notamment le lieu d'habitation, le statut de chômage, l'absence d'affiliation à une caisse d'assurance maladie, l'utilisation d'un schéma thérapeutique incluant une trithérapie, la survenue d'effets indésirables, le niveau d'éducation limité et une connaissance insuffisante de la maladie. En outre, la non-observance a été associée à un risque accru de rejet de greffe. Conclusion: Les résultats de cette étude révèlent une observance thérapeutique préoccupante chez les transplantés rénaux, soulignant l'importance cruciale de l'éducation thérapeutique afin de l'améliorer et mettant en évidence la nécessité d'intégrer ces facteurs dans la gestion clinique des patients.

Pharmaco-economic evaluation of kidney transplantation at the University Hospital Establishment of Oran: cost analysis and implications / Évaluation pharmaco-économique de la transplantation rénale à l'établissement hospitalier et universitaire d'Oran : analyse des coûts et implications.

Introduction: In Algeria, the number of patients treated by dialysis is estimated at 23,798 in 2019. Kidney transplantation is the best therapeutic option for patients suffering from end stage kidney Disease (ESKD). However, this procedure is costly and requires complex management. The aim of this study is to assess the costs associated with kidney transplantation at the University Hospital Establishment of Oran, Algeria (UHEO). Materials and methods: A retrospective, descriptive, monocentric study was carried out on 31 patients who underwent kidney transplantation at the UHEO. Estimated costs included drugs, consumables, imaging and laboratory tests for pre-transplant examinations, immediate post-transplant hospitalization, post-transplant follow-up and management of any complications. Results: The average cost of graft preparation was 485,438.31 Algerian Dinar (DZD). Immediate post-transplant hospitalization represented an average cost of 375,484.70 DZD. The first year post-transplantation was the most costly with an average cost of 1,305,197.40 DZD mainly attributed to treatment, hospitalization, clinical and paraclinical examinations. Conclusion: This study estimated the cost of kidney transplantation at the UHEO and revealed that the cost of the first year is the most important due to many factors. It also showed that costs tend to decrease with the age of the transplant and the clinical stability of the recipient.

Introduction: En Algérie, le nombre de patients traités par la dialyse est estimé à 23 798 en 2019. La transplantation rénale se positionne comme la meilleure option thérapeutique pour les patients atteints d'insuffisance rénale chronique terminale (IRCT). Cependant, cette procédure est coûteuse et nécessite une prise en charge complexe. Cette étude a pour objectif d'évaluer les coûts associés à la transplantation rénale à l'établissement hospitalier et universitaire d'Oran en Algérie (EHUO). Matériels et méthodes: Une étude rétrospective, descriptive et monocentrique a été menée sur 31 patients ayant subi une transplantation rénale avec un donneur vivant apparenté à l'EHUO. Les coûts estimés englobaient les médicaments, les consommables, l'imagerie et les bilans biologiques dans les examens pré-greffe du donneur et du receveur, l'hospitalisation post-greffe immédiate, le suivi post-greffe et la gestion d'éventuelles complications. Résultats: Le coût moyen de la préparation de la greffe était de 485 438,31 Dinar algérien (DZD). L'hospitalisation post-greffe immédiate a représenté un coût moyen de 375 484,70 DZD. La première année de la greffe était la plus coûteuse avec un coût moyen de 1 305 197,40 DZD principalement attribué au traitement, à l'hospitalisation et aux examens cliniques et paracliniques. Les infections urinaires, la Covid-19 et les complications chirurgicales étaient les complications les plus fréquentes. Une variabilité significative a été observée en fonction du type de complications allant de 1 785,48 à 654 214,60 DZD. Le rejet aigu du greffon a été associé au coût moyen le plus élevé. Conclusion: Cette étude a permis d'estimer le coût de la greffe rénale à l'EHUO et a révélé que le coût de la première année est le plus important en raison de plusieurs facteurs. Elle a également montré que les coûts ont tendance à diminuer au fur à mesure de l'ancienneté de la greffe et la stabilité clinique du receveur.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study.

BACKGROUND: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods. METHODS: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19. RESULTS: Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081-2.441). CONCLUSION: These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

Daratumumab treatment in six highly sensitised solid organ transplant recipients: A case series and literature review.

We report data on six kidney or heart recipients who were administered daratumumab to treat or prevent antibody-mediated rejection (ABMR). To date, data are scarce concerning the use of daratumumab in solid organ transplantation and most reports show a decrease in donor-specific antigen (DSA) levels and an improvement in ABMR using a multiple myeloma daratumumab administration scheme, that is, with sequential systematic administration. Here, we report on the efficacy of daratumumab 1/ in reducing the histological signs of ABMR, 2/ in reducing the ability of DSA to bind to donor cells in vitro through negativation of flow cytometry crossmatching, 3/ in preferentially being directed towards antibodies sharing epitopes, suggesting that daratumumab may specifically target activated plasma cells, 4/ and when administered as a single dose. This last point suggests, for the first time, that, as for rituximab in auto-immune diseases, the scheme for daratumumab administration could be different for targeting DSA-producing plasma cells than for tumour cells.

Transcriptomics-based identification of TYROBP and TLR8 as novel macrophage-related biomarkers for the diagnosis of acute rejection after kidney transplantation.

Macrophages play an important role in the development and progression of acute rejection after kidney transplantation. The study aims to investigate the biological role and significance of macrophage-associated genes (MAG) in acute rejection after kidney transplantation. We utilized transcriptome sequencing results from public databases related to acute rejection of kidney transplantation for comprehensive analysis and validation in animal experiments. We found that a large number of immune-related signaling pathways are activated in acute rejection. PPI protein interaction networks and machine learning were used to establish a Hub gene consisting of TYROBP and TLR8 for the diagnosis of acute rejection. The single-gene GSEA enrichment analysis and immune cell correlation analysis revealed a close correlation between the expression of Hub genes and immune-related biological pathways as well as the expression of multiple immune cells. In addition, the study of TF, miRNAs, and drugs provided a theoretical basis for regulating and treating the Hub genes in acute rejection. Finally, the animal experiments demonstrated once again that acute rejection can aggravate kidney tissue damage, apoptosis level, and increase the release of inflammatory factors. We established and validated a macrophage-associated diagnostic model for acute rejection after kidney transplantation, which can accurately diagnose the biological alterations in acute rejection after kidney transplantation.

A pig kidney supporting human physiology.

Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International assesses the kidney physiology of a porcine kidney transplanted into a brain-dead human with kidney failure, demonstrating life-sustaining physiological function for 7 days. Together with preclinical nonhuman primate studies, decedent models provide complementary data for development of clinical kidney xenotransplantation.

Herramientas para un ajuste de dosis de tacrolimus más personalizado en el seguimiento de los pacientes con transplante renal. Fenotipo metabolizador según polimorfismos genéticos del CYP3A vs. el cociente concentración-dosis / Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients: Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration–dose ratio

Antecedentes y justificación: La estrategia de la aproximación concentración-dosis (C/D) y los distintos perfiles del tacrolimus (Tac), según los polimorfismos del citocromo P450 (CYPs) se centran en el metabolismo de Tac y se plantean como herramientas para el seguimiento de los pacientes trasplantados. El objetivo de este estudio es comparar la exposición al Tac analizado según ambas estrategias. Materiales y métodos: Se han incluido 425 pacientes trasplantados renales. El cálculo del cociente concentración Tac/dosis (C/D) permitió dividir la población en terciles y clasificar los pacientes según su tasa de metabolismo del Tac en tres grupos (rápida, intermedia y lenta). Con base en los polimorfismos del CYP3A4 y A5, los pacientes se agruparon en metabolizadores rápidos (portadores del CYP3A5*1 y CYP34A *1/*1), intermedios (CYP3A5*3/3 y CYP3A4*1/*1) y lentos (CYP3A5 *3/*3 y portadores del CYP3A4*22). Resultados: Al comparar los pacientes de cada grupo metabolizador según los dos criterios, coincidieron 47% (65/139) de los metabolizadores rápidos, 85% (125/146) de los intermedios y solo 12% (17/140) de los lentos. Se observaron concentraciones de Tac estadísticamente menores en los metabolizadores rápidos y concentraciones mayores en los lentos, comparándolos con el grupo intermedio según el cociente C/D o según polimorfismos. Los metabolizadores rápidos requirieron alrededor de 60% más de dosis de Tac que los intermedios a lo largo del seguimiento, mientras que los lentos aproximadamente 20% menos de dosis que los intermedios. Los metabolizadores rápidos clasificados por ambos criterios presentan un porcentaje mayor de veces con valores de concentración de Tac en sangre infraterapéuticos... (AU)

Background and justification: The strategy of the concentration–dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. Materials and methods: Four hundred and twenty-five kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divided patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into three metabolizer groups: fast (CYP3A5*1 and CYP34A*1/*1 carriers), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). Results: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values... (AU)