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Background: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients., Methods: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival., Results: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up., Conclusion: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.

Background and Objectives: Dialysis patients have a high mortality risk after coronavirus disease 2019 (COVID-19) and an altered immunologic response to vaccines, but vaccine clinical effectiveness remains unknown in this population., Design, Setting, Participants, & Measurements: Using Bayesian multivariable spatiotemporal models, we estimated the association between vaccine exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severe infections (with hospital admission) in dialysis patients from simultaneous incidence in the general population. For dialysis patients, cases were reported within the French end-stage kidney disease REIN registry from March 11, 2020, to April 29, 2021, and vaccine exposure (first dose) was reported in weekly national surveys since January 2021. Cases in the general population were obtained from the national exhaustive inpatient surveillance system (SI-VIC database), and vaccination coverage (first dose) was obtained from the national surveillance system (VAC-SI database)., Results: During the first wave, incidence in dialysis patients was approximately proportional to the general population. However, we showed a lower relative incidence for dialysis patients during the second wave (compared with that observed in nondialysis patients), suggesting an effect of prevention measures. Moreover, from the beginning of the vaccination rollout, incidence in dialysis patients was lower compared with predictions based on the first and second waves. Adding vaccination coverages in dialysis and nondialysis patients as predictors allowed the reported cases to be fit correctly (3685 predicted cases, 95% confidence interval, 3552 to 3816, versus 3620 reported). Incidence rate ratios were 0.37 (95% confidence interval, 0.18 to 0.71) for vaccine exposure in dialysis patients and 0.50 (95% confidence interval, 0.40 to 0.61) per 10% higher in vaccination coverage in the same-age general population, meaning that vaccine exposure in dialysis patients and the general population was independently associated with lower hospitalization rate of dialysis patients., Conclusions: Our findings suggest that vaccination may yield a protective effect against severe forms of COVID-19 in dialysis patients, despite altered immunologic vaccine responses., (Copyright © 2022 by the American Society of Nephrology.)

The Covid-19 pandemic hits the French transplant population on March 3, 2020. Very quickly, a French registry was set up on behalf of the French Society of Transplantation allowing the collection of confirmed cases of Covid-19 occurring in kidney transplant recipients in almost all French centers. The analysis of this registry in conjunction with the data from the Agence de la Biomédecine (Cristal) has enabled us to obtain instructive results. We first showed that the incidence of severe forms among transplant patients hospitalized for Covid-19 was 46% and that their mortality was 22.8%. The risk factors for severe forms and mortality are described. Then we showed, by comparing transplant patients with immunocompetent patients matched for the main severity factors of the disease, that mortality among transplant patients was higher (17.9% vs 11.4%; P<0.001). In multivariate analysis, a creatinine level at admission above 115 μmol/L was associated with death, whereas being transplanted was not. Finally, comparing the transplant cohort with patients on the kidney transplant waiting list during the period from February to June 2020, we found that patients on the waiting list had a higher Covid-19-related excess mortality than transplant patients, mainly in areas of low viral circulation. In conclusion, the French Registry of transplant patients with Covid-19, which was rapidly set up at the beginning of the epidemic, has already enabled us to draw several lessons about this initially unknown infection, particularly in kidney transplant patients, a population which appeared to be particularly at risk., (Copyright © 2021 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Background: Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in organ transplant recipients remains limited. The aim of this registry-based observational study was to report the characteristics and clinical outcomes of liver transplant (LT) recipients included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19., Methods: COVID-19 was diagnosed in patients who had a positive PCR assay for SARS-CoV-2 or in presence of typical lung lesions on imaging or specific SARS-CoV-2 antibodies. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded., Results: Of the 104 patients, 67 were admitted to hospital and 37 were managed at home (including all 13 children). Hospitalized patients had a median age of 65.2 years (IQR: 58.1 - 73.2 years) and two thirds were men. Most common comorbidities included overweight (67.3%), hypertension (61.2%), diabetes (50.7%), cardiovascular disease (20.9%) and respiratory disease (16.4%). SARS-CoV-2 infection was identified after a median of 92.8 months (IQR: 40.1 - 194.7 months) from LT. During hospitalization, antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. The composite endpoint of severe Covid-19 within 30 days after diagnosis was reached by 33.0% of the adult patients. The 30-day mortality rate was 20.0%, and 28.1% for hospitalized patients. Multivariate analysis identified that age was independently associated with mortality., Conclusion: In our large nationwide study, Covid-19 in LT recipients was associated with a high mortality rate., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Malaria, a potentially life-threatening disease, is the most prevalent endemic infectious disease worldwide. In the modern era, the spectrum of glomerular involvement observed in patients after malarial infections remains poorly described., Design, Setting, Participants, & Measurements: We therefore performed a retrospective multicenter study to assess the clinical, biologic, pathologic, and therapeutic characteristics of patients with glomerular disease demonstrated by kidney biopsy in France within 3 months of an acute malaria episode., Results: We identified 23 patients (12 men), all but 1 of African ancestry and including 10 patients with concomitant HIV infection. All of the imported cases were in French citizens living in France who had recently traveled back to France from an endemic area and developed malaria after their return to France. Eleven patients had to be admitted to an intensive care unit at presentation. Plasmodium falciparum was detected in 22 patients, and Plasmodium malariae was detected in 1 patient. Kidney biopsy was performed after the successful treatment of malaria, a mean of 24 days after initial presentation. At this time, all patients displayed AKI, requiring KRT in 12 patients. Nephrotic syndrome was diagnosed in 17 patients. Pathologic findings included FSGS in 21 patients and minimal change nephrotic syndrome in 2 patients. Among patients with FSGS, 18 had collapsing glomerulopathy (including 9 patients with HIV-associated nephropathy). In four patients, immunohistochemistry with an antibody targeting P. falciparum histidine-rich protein-2 demonstrated the presence of the malaria antigen in tubular cells but not in podocytes or parietal epithelial cells. An analysis of the apoL1 risk genotype showed that high-risk variants were present in all seven patients tested. After a mean follow-up of 23 months, eight patients required KRT (kidney transplantation in two patients), and mean eGFR for the other patients was 51 ml/min per 1.73 m 2 ., Conclusions: In patients of African ancestry, imported Plasmodium infection may be a new causal factor for secondary FSGS, particularly for collapsing glomerulopathy variants in an APOL1 high-risk variant background., (Copyright © 2020 by the American Society of Nephrology.)

Background: Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown., Methods: Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study., Results: An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P < 0.001) than non-infectious diarrhoea. However, the non-infectious group had lower death-censored graft survival than the infectious group (Gehan-Wilcoxon test, P = 0.038). Multivariate analysis retained three independent predictors of graft failure after diarrhoea: diarrhoea occurring ≥5 years after KT [hazard ratio (HR) 4.82; P < 0.001], re-transplantation (HR 2.38; P = 0.001) and baseline estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 11.02; P < 0.001)., Conclusion: Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Transplant center organization, that is a modifiable factor, may affect the access to living-donor kidney transplantation (LDKT). The objective of this study was to identify the center characteristics associated with LDKT using a hierarchical analysis. This was a retrospective multicenter observational study of 8701 patients who received a first renal graft between 2010 and 2014 in 32 transplantation centers of France. Hierarchical modeling was used to estimate the center effect and organization associated with LDKT. Among 8507 patients, 1225 (12%) were transplanted with a LD kidney. There was a transplant center effect on the proportion of LDKT. After adjustment for patient and center characteristics, the random effect variance decreased by 47%. Patients transplanted at a center with more than four nephrologists [1.81 (95% CI: 1.10-2.95)] and more than 1.5 nurse transplant coordinators [1.98 (95% CI: 1.26-3.13)] were more likely to be transplanted with a LD kidney. ABO-incompatible program was associated with LDKT [2.23 (95% CI: 1.22-4.06)]. There was a transplant center effect on the proportion of LDKT that could be decreased by modifiable center characteristics. Our study suggests the importance of the transplant team organization on the LDKT utilization., (© 2019 Steunstichting ESOT.)

Following the publication of the ministerial action plan setting goals for the next five years, we performed a survey regarding the human resources and work organizations in the French renal transplant centers (n=33) on behalf of French speaking society of nephrology dialysis and transplantation (SFNDT). While the renal transplantation activity has been raising last years, we describe that the most active centers frequently resorted to an on-site nephrology guard and a surgeon dedicated to the transplantation activity, whereas only eight centers have a non restricted access to an operating room. Since 2002, the number of transplantations and follow-up visits performed by one nephrologist (full-time equivalent) have increased by 20 and 11%, respectively, while patient monitoring after transplantation is claimed to be shared with partner health centers in 94% of the transplant centers. Thus, the number of patients per nephrologist has increased when the active list exceeds 1150 patients in a center, e.g., 45% of centers in 2016 and 70% of centers in 2021 if the objectives are achieved. This survey also showed the stagnation of the specialized paramedical staff. Finally, the survey shows that the two main hurdles to the development of living donor transplantation are the availability of operating rooms and the lack of paramedical employees. In conclusion, this survey shows that an increase in the number of medical, surgical and paramedical staff will be necessary to achieve departmental objectives., (Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: During year 2013, 5943 tests for antineutrophil cytoplasmic antibodies (ANCA) detection were performed in Bordeaux hospital, France. This seemed disproportionate, with regard to the low prevalence of ANCA-associated vasculitis (AAV). Our purpose was to evaluate the relevance of these requests., Methods: Requests for detection of ANCA during 2013 were recorded, with their results. A sample of 501 requests was secondarily established. Relevance of requests was assessed independently by two reviewers. During year 2014, we developed strategies of information, in order to reduce the number of requests and increase their relevance., Results: Only 17.8 % of the 5943 requests for detection of ANCA resulted in a positive test using indirect immunofluorescence (including 10.6 % of the requests with titles above 1/50). Using Luminex©, 9.7 % of the test of detection against antimyeloperoxidase or antiproteinase 3 antibodies were positive. Within the sample of 501 patients, only 28.7 % of the requests were relevant. A percentage of 40.2 of them weren't justified by a clinical affection typically associated with AAV. Exactly 15.9 of the requests were performed during systematic autoimmune screening. None of these requests could lead to the diagnosis of AAV. Combination of information procedures and use of a request form enabled a 19 % decrease of the number of requests. The percentage of requests without clinical justification also reduced from 40.2 % to 17.1 %. The reduction of the number of requests led to a 46,865 € saving., Conclusion: The majority of the requests for detection of ANCA was not relevant and could not lead to the diagnosis of AAV. Simple solutions enabled a partial but significant improvement of their relevance., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently, it has also been used in the treatment of several autoimmune diseases., Patients and Methods: We conducted a retrospective analysis of patients treated at least once with rituximab between 2010 and 2013 in a French university hospital, to provide a panoramic view of rituximab use including FDA or off-labels uses, its efficacy and safety., Results: Eighty-seven patients were included with 20 different indications: cryoglobulinemic vasculitis (16%) and anti-PLA2R idiopathic membranous nephropathy (13%) were the most frequent. Rituximab use was off-labels in 50% of cases. Eleven percent of patients experienced severe adverse events, mostly infections. After rituximab, 17% of patients were in complete response (CR), 41% in partial response (PR), and 39% non-responding (NR). Relapse was observed in 65% (33/51) of responding patients., Conclusion: Further investigation with randomized controlled trials will provide more insight into the specifics of the role of RTX in the overall management of each disease. Identifying clear objectives and strict outcome measures, associated with long term clinical and biological follow-up would help deciding when, how and in which therapeutic regimen will rituximab most benefit a disease or a patient., (Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: There have been few prospective studies on the natural history of nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective of this study was to prospectively evaluate the rate of and risk factors for NA in a French cohort of KTRs., Method: A total of 312 KTRs from eight French transplantation centers were included in this prospective, noninterventional cohort study. A computer-learning software package (the Organ Transplant Information System) was made available to all patients., Results: Using the four-item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively. Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple treatment regimens including a small number of doses per day and a small number of tablets per day were associated with NA at M3 and M12, respectively. Other factors predictive of NA included failure to use the Organ Transplant Information System software package at M6 and patient reports of adverse events at M12 and M24. Importantly, we observed that physicians underestimated the prevalence of adverse events when compared to patient self-reporting., Conclusion: Our observed rate of medication NA in France is consistent with rates reported in previous studies. We found variability in NA risk factors over time as well as an unexpected risk factor (simple treatment regimens). These findings will be useful in developing effective adherence-promoting interventions.

Background: Concerns about delayed graft function (DGF) and wound healing complications with sirolimus has led to suggestions that everolimus introduction could be delayed after transplantation., Methods: In a prospective, multicenter, open-label study, deceased-donor kidney transplant recipients at protocol-specified risk of DGF (defined as > or =1 dialysis session during the first week posttransplant excluding day 1) were randomized to start everolimus therapy on day 1 posttransplant (immediate everolimus [IE]), or from week 5 (delayed everolimus [DE]) with mycophenolic acid until everolimus was initiated. All patients received anti-interleukin-2 receptor antibodies, cyclosporine A, and corticosteroids. A planned 3-month analysis from this 12-month study is presented here., Results: One hundred and thirty-nine patients were randomized (IE 65, DE 74). The primary composite endpoint: biopsy-proven acute rejection, graft loss, death, DGF, wound healing events, or lost to follow-up at month 3, occurred in 36 IE patients (55.4%) and 47 DE patients (63.5%, P=0.387). The incidence of DGF was similar between groups (IE 24.6%, DE 24.3%; n.s.). Wound healing events of any type occurred in 40.0% and 41.9% of IE and DE patients (n.s.); events relating to initial transplant surgery occurred in 36.9% IE patients and 37.8% DE patients (n.s.), most of which were fluid collections. Study drug was discontinued due to adverse events or graft loss in 13 IE (20.0%) and 17 DE patients (23.0%)., Conclusions: Findings from this randomized, multicenter trial indicate that kidney function recovery, wound healing, efficacy, and tolerance are similar at 3 months posttransplant with immediate or DE in patients at protocol-specified risk of DGF.