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Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

Introduction Various surgical centers tend to postpone a kidney transplantation (KT) to the following morning than to operate at night‐time. The objective of our study was to assess whether there was any difference between daytime and night‐time renal transplantation in our institution. Method This study is a retrospective monocentric study including all the KTs that were performed between 2012 and 2013 by transplant expert surgeons in our institution. Clavien‐Dindo (CD) complications were classified according to 7 variables going from 1 to 5. Time before postgraft diuresis and delayed graft function (DGF) were also analyzed. Two groups of patients were formed according to threshold value of incision time (6.30 p.m.). Data comparison were performed using the Kruskal–Wallis nonparametric test. Results A total of 179 patients were included. Median follow‐up was 24 months. Cold ischemia time was longer in the night‐time transplantation (1082 vs. 807 min, p, Graphical abstract

International audience; Background and objectives The fact that metabolism and immune function are regulated by an endogenous molecular clock that generates circadian rhythms suggests that the magnitude of ischemia reperfusion, and subsequent inflammation on kidney transplantation, could be affected by the time of the day. Design, setting, participants, & measurements We evaluated 5026 individuals who received their first kidney transplant from deceased heart-beating donors. In a cause-specific multivariable analysis, we compared delayed graft function and graft survival according to the time of kidney clamping and declamping. Participants were divided into those clamped between midnight and noon ( ante meridiem [ am ] clamping group; 65%) or clamped between noon and midnight ( post meridiem [ pm ] clamping group; 35%), and, similarly, those who underwent am declamping (25%) or pm declamping (75%). Results Delayed graft function occurred among 550 participants (27%) with am clamping and 339 (34%) with pm clamping (adjusted odds ratio, 0.81; 95% confidence interval, 0.67 to 0.98; P =0.03). No significant association was observed between clamping time and overall death-censored graft survival (hazard ratio, 0.92; 95% confidence interval, 0.77 to 1.10; P =0.37). No significant association of declamping time with delayed graft function or graft survival was observed. Conclusions Clamping between midnight and noon was associated with a lower incidence of delayed graft function, whereas declamping time was not associated with kidney graft outcomes.

Kidney transplantation (KT) can impact patients’ evaluation of health-related quality of life (HRQoL) as they adapt to their new life with a graft and its changes. Patients may adapt to KT in a different way, depending on whether they were on dialysis prior to transplantation or not (i.e. preemptive group). This may result in lack of measurement invariance between these patients’ groups and/or over time (i.e. response shift, RS) which may invalidate the between-group comparison of HRQoL change scores. The aim of this study was to investigate and compare RS before and after KT between these two patients’ groups. Measurement invariance was investigated between groups and over time with three measurement occasions. Adult patients completed the SF-36 at the last visit before KT, and 3, 6 months after. A structural equation model-based procedure was used to (i) detect and take into account measurement non-invariance between groups and RS, if appropriate, (ii) identify the period of occurrence of RS, (iii) study the heterogeneity of RS between the two groups. Before KT (i.e. baseline), measurement invariance was not rejected between dialyzed (n = 196) and preemptive (n = 178) patients’ groups. Between baseline and 3 months after KT, similar uniform recalibration was detected on the general health domain in both groups. Uniform recalibration was found between 3- and 6 months after KT on the vitality domain for preemptive patients only. HRQoL, adjusted for RS, increased overall for preemptive and dialyzed kidney transplant patients after transplantation. RS may reflect differing adaptation processes following KT.

International audience; Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is 55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.

Background Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies. Methods This prospective pilot randomized French multicenter study aimed to compare anti–T-lymphocyte Ig (ATLG) (n = 32) and basiliximab (n = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included. Results Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%–37.1%) and 18.8% (95% CI, 8.9%–37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%–34.8%) and 28.2% (95% CI, 14.2%–51.2%) of patients who received basiliximab, respectively at 6 (P = 0.66) and 12 (P = 0.62) months post-transplantation. One T cell–mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a de novo donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups. Conclusion This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution., Graphical abstract

Background: Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, which uses MeltDose™ drug-delivery technology to control drug release and enhance overall bioavailability. Our study compared dosing of LCPT with current standard-of-care tacrolimus [immediate-release tacrolimus (IR-Tac) or prolonged-release tacrolimus (PR-Tac)] during the 6 months following de novo kidney transplantation. Comparisons of graft function, clinical outcomes, safety, and tolerability for LCPT versus IR-Tac/PR-Tac were also performed.Methods: Standard immunological risk patients with end-stage renal disease who had received a de novo kidney transplant were randomized (1:1) to LCPT (N = 200) or IR-Tac/PR-Tac (N = 201).Results: Least squares (LS) mean tacrolimus total daily dose from Week 3 to Month 6 was significantly lower for LCPT than for IR-Tac/PR-Tac. Although LS mean tacrolimus trough levels were significantly higher for LCPT than IR-Tac/PR-Tac, tacrolimus trough levels remained within the standard reference range for most patients. There were no differences between the groups in treatment failure measures or safety profile.Conclusion: LCPT can achieve similar clinical outcomes to other tacrolimus formulations, with a lower daily dose.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT02432833.

BackgroundMost studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys.MethodsThe analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan–Meier estimators, weighted on the propensity score, were used to study the times-to-events.ResultsAmong the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4–6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7–6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h.ConclusionsOur study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (dnDSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dnDSA generation, acute rejection and GF. Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dnDSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dnDSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dnDSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dnDSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dnDSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dnDSA occurrence, and acute rejection. Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dnDSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF.

Background and Aims IgA Nephropathy (IgAN) often recurs on kidney transplants, accounting for a significant specific kidney failure occurrence after ten years of transplantation vintage. Polyclonal anti-T-lymphocyte antibodies (PATLA) immunosuppressive induction has been shown to be associated with a lower rate of IgAN recurrence compared to basiliximab and no induction in a retrospective study. The aim of the PIRAT study was to compare an induction by PATLA versus basiliximab by the mean of a randomized controlled trial. Method Adults with biopsy-proven primary IgAN as primary cause of end stage of renal disease, first transplantation, panel reactive antibody 300mg/d during 5 years post-transplantation. Protocol biopsy at 5 years was highly recommended. Results A total of 117 patients were finally included in 13 French transplant centers, with 60 patients in the PATLA group and 57 in the basiliximab control group. Both groups were similar (median, PATLA vs. basiliximab, p>0.05 wilcoxon test) in term of sex ratio (4.45 vs 4.57), recipient age (47.9 vs. 47.7 years old), dialysis vintage (26.2 vs. 24.6 months), age at IgAN diagnosis (35.0 vs. 42.2 years old), cold ischemia (780 min vs 682 min), warm ischemia (34 vs. 36.1min), proportion of living donors (33% vs. 25%). The 5-year protocol biopsy was performed on 48% vs. 45% of patients, with overall proportion of patients evaluated by at least one biopsy of 63% vs. 66%. A trend in favor to the protection by PATLA from the occurrence of a clinico-histological recurrence was found (hazard ratio, univariate Cox model 0,35 [0.11-1.1], p=0.082). Biopsy proven histological recurrence was significantly lower after PATLA induction (HR 0.34 [0.16-0.76], p=0.0079). PATLA group experienced more infections (40 vs. 28 p=0.06), a lower number of graft losses (3 vs 9, p=0.07), a lower number of biopsy-proven acute rejections (5 vs 10, p=0.17). Similar rates of cytomegalovirus and BK virus infections were found. Conclusion PATLA for immunosuppressive induction was found protective from the recurrence of IgA deposition during the first 5 years after transplantation, compared to basiliximab. A similar trend, although not significant, was found about the clinico-histological recurrence which was the predefined primary outcome.

International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

Objectifs Les patients en insuffisance renale terminale avec un CaP represente un dilemme de priorisation de traitement. Le traitement immunosuppresseur d’induction par Thymoglobulines expose les patients a un sur-risque d’infections et de tumeurs malignes. L’objectif de notre etude etait de comparer les Resultats oncologiques de patients avec CaP localise selon qu’ils aient ete greffes avant ou apres le traitement de leur CaP et de definir l’impact des Thymoglobulines sur la survenue ou la recidive d’un CaP en post greffe Methodes Il s’agit d’une etude retrospective monocentrique analysant les patients ayant une GR et un CaP de 1995 a 2020. Deux groupes ont ete constitues en fonction de leur sequence therapeutique : GR puis CaP (groupe 1) et inversement (groupe 2) ( Tableau 1 ). Pour la premiere question et deux groupes etaient definis suivant leur immunotherapie a l’induction pour la deuxieme question : Basiliximab (groupe 1) ou Thymoglobulines (groupe 2) ( Tableau 2 ). Le critere de jugement principal etait la recidive biologique (RB) du CaP pour les deux questions. Les criteres secondaires pour la premiere question concernaient la creatininemie, le taux de retour en dialyse, la survie du greffon et la survie globale et pour la deuxieme question le delai d’apparition du CaP par rapport a l’induction, la creatininemie apres GR, la survie du greffon et la survie du patient. Resultats Pour la premiere question 30 patients ont ete inclus, avec une egale repartition entre les groupes. Le suivi median etait de 9,83 ans [7,19–14,69]. La duree de dialyse est plus longue (3,96 vs 2,24 ans [p = 0,057]) et la survie du greffon plus courte (8,92 vs 5,06 ans (p = 0,005)) dans le groupe 2 par rapport au groupe 1. On ne rapportait pas de difference significative de RB du CaP avec n = 2/15 (13,3 %) et n = 3/15 (20 %) cas dans les groupes 1 & 2 respectivement (p = ns) ( Tableau 1 ). Pour la deuxieme question 24 patients ont ete inclus, 14 dans le groupe 1 et 10 dans le groupe 2. Le taux de RB etait similaire avec 2 (14,3 %) cas et 1 (10 %) cas dans les groupes 1 et 2 respectivement (p = 1) ( Tableau 2 ). Le delai de survenu du CaP apres GR tendait a etre plus precoce dans le groupe Thymoglobulines que dans le groupe Basiliximab (2,4 ans vs 6,2 ans respectivement [p = 0,089]). Conclusion Le delai necessaire entre la guerison du CaP et la possibilite de greffe majore le temps passe en dialyse avec ses repercussions sur la survie du greffon. Sans modifier les resultats oncologiques, priorite pourrait etre donnee a la GR en cas de CaP chez un patient en attente de GR sous reserve d’etude a plus grande echelle. Le type d’induction ne modifierait pas l’incidence du CaP chez les GR, mais les Thymoglobulines pourraient favoriser sa survenue plus precoce.

Background Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up. Methods Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007–11 and 2012–17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4. Results We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors Conclusions An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.

BackgroundThe increased survival of patients with multiple myeloma (MM) raises the question of kidney transplantation (KT) in patients with end-stage renal disease (ESRD).MethodsWe included 13 patients with MM or smoldering myeloma (SMM) and ESRD transplanted between 2007 and 2015, including 7 MM with cast nephropathy, 3 with MM-associated amyloid light chain amyloidosis or light chain deposition disease and 3 SMM and compared them with 65 control-matched kidney-transplanted patients. Nine of the MM patients with KT were also compared with 63 matched MM patients on haemodialysis.ResultsPre-transplantation parameters were comparable, except for the duration of renal replacement therapy (57.8 versus 37.0 months; P = 0.029) in MM versus control patients, respectively. The median follow-up post-KT was 44.4 versus 36.4 months (P = 0.40). The median MM graft and patient survival were 80.1 and 117.2 months, respectively, and were not significantly different from control patients, although mortality tended to be higher in the 10 symptomatic MM patients (P = 0.059). MM patients had significantly more viral and fungal infections and immunosuppressive maintenance therapy modifications while they received lower induction therapy. Two MM patients relapsed and two SMM cases evolved to MM after KT. Three cast nephropathies occurred, two of them leading to ESRD. Moreover, survival of MM with KT increased relative to control haemodialysed patients (P = 0.002).ConclusionsSelected MM patients may benefit from KT but need careful surveillance in the case of KT complications and MM evolution.

IntroductionExpanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysisHYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and disseminationThe trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration numberNCT03098706.

Background. Whilst there are numbers of publications comparing the relationship between the body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study was performed in French patients. Methods. In this study, cause-specific Cox models were used to study patients and graft survival and several other different times-to-event. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. Results. Among the 4691 included patients, 747 patients were considered obese with a BMI level higher than 30 kg/m². We observed a higher mortality of obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p

Background This post hoc analysis of data from the prospective OSAKA study evaluated the efficacy and safety of prolonged- and immediate-release tacrolimus in patients who received kidneys from extended-criteria (ECD) and standard-criteria (SCD) donors. Material/Methods Within the ECD and SCD groups, patients were randomized to one of 4 tacrolimus-based regimens (initial dose): Arm 1, immediate-release tacrolimus (0.2 mg/kg/day); Arm 2, prolonged-release tacrolimus (0.2 mg/kg/day); Arm 3, prolonged-release tacrolimus (0.3 mg/kg/day); Arm 4, prolonged-release tacrolimus (0.2 mg/kg/day) plus basiliximab. All patients received mycophenolate mofetil and bolus corticosteroids; Arms 1–3 also received tapered corticosteroids. ECDs met the definition: living/deceased donors aged ≥60 years, or 50–60 years with ≥1 other risk factor, and donation after circulatory death. Primary composite endpoint: graft loss, biopsy-confirmed acute rejection or renal dysfunction by Day 168. Outcomes were compared across treatment arms with the chi-squared or Fisher’s exact test. Results A total of 1198 patients were included in the analysis (ECD: n=620 [51.8%], SCD: n=578 [48.2%]). Patients with kidneys from ECDs were older versus SCDs (mean age, 55.7 vs. 44.5 years, p

Cytomegalovirus (CMV) is the most common viral pathogen in kidney transplant recipients (KTRs), and CMV disease impacts patient and graft survivals. CMV-specific CD8 T cell mediated–immunity (CMI) may help to assess the risk of CMV disease and to adapt preventive treatment strategies. High-risk KTRs with CMV seropositive donors/seronegative recipients (D+/R−) were prospectively monitored after CMV prophylaxis discontinuation and during the first year post transplant for CMV viremia (World Health Organization standardization) and CMI (QuantiFERON-CMV). We analyzed the ability of CMI test to predict either subsequent spontaneous viral clearance or CMV disease after prophylaxis discontinuation in patients with asymptomatic viremia. We enrolled 12 consecutive (D+/R−) KTRs. Eleven patients developed a viremia during follow-up, but 7 of them (64%) exhibited a spontaneous viral clearance. At viremia onset, 6 of 11 patients (55%) had a positive CMI test, and all of them (6 of 6, 100%) had subsequent spontaneous viral clearance, compared with only 1 of 5 patients (20%) displaying a nonreactive CMI (P = .02). This latter patient exhibited a positive CMI test 15 days after viremia onset. Four of the 11 patients (36%) developed a CMV disease, and their CMI either remained nonreactive or became positive only after antiviral treatment. We conclude that D+/R− KTRs with asymptomatic viremia after prophylaxis discontinuation may benefit from QuantiFERON-CMV to predict when positive for the spontaneous viral clearance or when persistently negative or the development of a CMV disease.

Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period.. Initial kidney disease was scleroderma renal crisis in 76.4%. Extra-renal involvement of SS was generally stable, excepted cardiac and gastro intestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3, and 5 years post transplant respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in 3 cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extra-renal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation. This article is protected by copyright. All rights reserved.

International audience; The prognosis of sickle cell disease (SCD) patients who need dialysis is poor, but experience with kidney transplantation is limited. This study assessed the characteristics of 36 SCD patients undergoing renal transplantation. Immediate post-surgical complications occurred in 25% of cases. Cytomegalovirus and bacterial infections were frequently observed. Twelve patients died after a median follow-up period of17-4 months. Overall patient survival was significantly lower in SCD than in the control group without significant difference for overall death-censored graft sur-vival. Our data suggest that renal transplantation should be systematically considered in SCD patients with end-stage renal disease.

International audience; BACKGROUND: A significant number of studies have compared graft outcomes between patients with Pre-emptive Kidney Transplantation (PreKT) and patients on Dialysis before their Kidney Transplantation (DiaKT). These studies have suffered from the limitation that the DiaKT group is composed of all the dialysed patients, including those placed on a waiting list at the time of their first dialysis session. This seriously questions the comparability of these patients with those placed on the waiting list a long time before the need for renal replacement therapy. The aim of this study was to precisely evaluate the causal effect of PreKT from deceased donors.METHODS: Data were extracted from the multicentric French DIVAT (Données Informatisées et VAlidées en Transplantation) cohort. The DiaKT group was composed of patients placed on the waiting list with an initial intention of pre-emptive transplantation. Cause-specific Cox models with propensity scores (inverse probability weighting) were used to study the patient and graft outcomes.RESULTS: Among the 1138 included patients, 554 patients were in the PreKT group. The outcomes of the PreKT group were similar compared with the DiaKT group. In particular, the life expectancy with a functioning graft was 8.51 years [95% confidence interval (CI) 8.20-8.81] for the PreKT recipients versus 8.49 years (95% CI 8.15-8.84) for the DiaKT recipients.CONCLUSIONS: Our results challenge the utility of PreKTs from deceased donors, especially with regard to the consequential increase in the waiting list.

INTRODUCTION AND OBJECTIVES:Dual kidney transplantation (DKT) is an underused way to address graft shortage, allowing elderly patients to get quickly a kidney transplant. The choice between the ips...

Background: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make possible to target a population at risk to develop de novo diabetes. We hypothesized that a short term treatment with Vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. Methods: This is a multicenter double-blind placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included in 10 French transplant center. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating blocks) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, or/and with an abnormal oral glucose tolerance test. Secondary outcomes include the glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months and 12 months after transplantation. The results will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, the health-related quality of life and the cost-effectiveness of prevention of diabetes with vildagliptin. Discussion: There are only few data concerning pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities. Trial registration: ClinicalTrials.gov, NCT02849899 Registered on 8 February 2016. Keywords: Diabetes prevention; Vildagliptin; kidney transplantation; randomized controlled trial.

Background: Ureteral stenosis is part of the common complications of renal graft reported in 3% to 7% of cases. Multiple treatments have been introduced regarding length and position of the stenosis. Metal stents for urologic purpose were created in 1998. Double percutaneous antegrade and transurethral retrograde access to a ureteral stenosis to a long-term metal stent procedure has been rarely described. Case Presentation: Here, we present a case of a ureteral stricture in a double ipsilateral kidney graft with a common ureter. A 67-year-old patient presented with obstructive nephritis associated with acute renal failure 6 years after a double renal graft with a uretero-ureteral end-to-side anastomosis. Abdominal CT scan showed double pelvic dilation. The patient underwent double percutaneous nephrostomies and antegrade pyelogram showed both renal pelvic and ureter dilations caused by a severe chronic ureteral stenosis at junction into the bladder. A Double-J ureteric stent was then inserted retrogradely over a guidewire as first-line treatment. Due to recurrent urinary tract infections (UTIs), removal and replacement of Double-J stents were carried out by placing a thermoexpandable metal stent Memokath® 051 (Bard, Pnn Medical) through the common ureter by a double antegrade and retrograde approach. Treatment was effective with a good renal function maintained after a 3-year follow-up without UTIs. Conclusion: Double antegrade and retrograde access to a long-term metal stent treatment can be seen as an alternative treatment to either endoscopy or open surgery. Further studies should be continued using larger series.

Introduction De fortes doses de vitamine D3 (cholecalciferol, CL) ont ete preconisees pour reduire le risque de diabete de type 2, d’evenements cardiovasculaires majeurs (MACE) et de cancer, qui sont des complications frequentes chez les patients transplantes renaux (PTR). Patients/Materiels et methodes L’etude VITALE est un essai prospectif, multicentrique (30 departements Francais), en double aveugle, controle (NCT01431430). Les PTR adultes ayant des concentrations seriques de 25(OH)-vitamine D (25OHD) Observation/Resultats Entre janvier 2012 et decembre 2013, 536 PTR (âge moyen [ecart type] 50,8 [13,7] ans, 335 hommes) ont ete inclus. Les caracteristiques cliniques et biologiques de depart ne differaient pas entre les groupes DE (n = 269) et DF (n = 267). Dans les groupes DE et DF, la 25OHD etait de 20,2 (8,1) versus 19,2 (7,0) ng/mL a j0 et de 43,1 (12,8) versus 25,1 (7,4) ng/mL apres 24 mois, respectivement (p Discussion Nous rapportons les resultats du premier essai interventionnel visant a evaluer les effets extra-osseux du traitement par vitamine D3 apres transplantation renale. Le nombre de patients inclus correspond a notre objectif initial. Conclusion Par rapport aux ANC, de fortes doses de CL n’induisent pas d’effets indesirables notables mais ne reduisent pas l’incidence des complications non squelettiques apres transplantation renale.

Angioplasty with or without stenting has become a well-established procedure to treat transplant renal artery stenosis (TRAS). We evaluated our experience on postoperative outcomes following the intervention and identified potential predictive factors of TRAS recurrence. Consecutive patients who underwent endovascular treatment of TRAS were retrospectively reviewed. The study end points were the technical success, 30-day postoperative complications, and the estimated glomerular filtration rate (eGFR). Thirty-two patients underwent endovascular treatment for TRAS. The technical success rate was 96.6%. Complications were observed for 7 (21.9%) patients: 4 had a dissection, 2 a pseudoaneurysm, and 1 (3.1%) patient developed an acute pulmonary edema. The mean eGFR significantly increased at 7 days, 3 months, and 6 months postintervention (43.1, 44.9, and 44.3 vs 33.9 mL/min/1.73 m2preoperatively, P < .05). The TRAS recurrence was observed in 7 (21.9%) patients. These patients had significantly higher preoperative peak systolic velocity and systolic rise time (5 vs 4 m/s, P = .0383 and 103 vs 80 milliseconds, P = .0148, respectively). Endovascular treatment of TRAS is associated with high technical success and significant improvement in renal function. Further studies are required to confirm predictive factors of TRAS recurrence following endovascular treatment.

Introduction Le pyrophosphate (PPi) est un agent anti-calcifiant dont les concentrations plasmatiques ([PPi]pl) sont diminuees de moitie chez les patients hemodialyses par rapport aux sujets sains. Le PPi provient de l’ATP extracellulaire et de l’absorption digestive. Il est hydrolyse par les phosphatases alcalines (PAL) et/ou elimine par les reins. Notre hypothese est que l’augmentation de l’activite des PAL (aPAL) liee a l’osteodystrophie renale expliquerait la baisse des [PPi]pl en dialyse et que la greffe renale augmenterait les [PPi]pl en normalisant aPAL. Methodes Les marqueurs du metabolisme mineral ont ete mesures chez des sujets sains (T), des patients hemodialyses (HD) et des patients transplantes renaux (TR). Les variables ont ete exprimees en mediane et interquartiles [25e–75e] et comparees entre elles. Resultats obtenus ou attendus L’etude comportait 10 T, 10 HD, 10 TR 2 ± 1 mois et 9 TR 24 ± 3 mois apres transplantation. Les [PPi]pl etaient abaissees chez les HD (1,05 [0,88–1,35] μmol/L) et chez les TR 2 ± 1 mois (0,93 [0,66–0,98] μmol/L) par rapport aux T (1,57 [1,31–1,72] μmol/L ; p Conclusion L’augmentation d’aPAL est bien associee a la baisse des [PPi]pl. A niveau d’hydrolyse equivalent, les [PPi]pl restent basses 2 ans apres une greffe de rein. L’absence d’elimination renale accrue de PPi suggere un defaut de production ou d’absorption de PPi chez les greffes. Des etudes seront necessaires pour caracteriser la production du PPi et son assimilation digestive chez les greffes.

Markers of epithelial-mesenchymal transition (EMT) may identify patients at high risk of graft fibrogenesis who could benefit from early calcineurin inhibitor (CNI) withdrawal. In a randomized, open-label, 12-month trial, de novo kidney transplant patients received cyclosporine, enteric-coated mycophenolate sodium (EC-MPS) and steroids to month 3. Patients were stratified as EMT+ or EMT- based on month 3 biopsy, then randomized to start everolimus with half-dose EC-MPS (720 mg/day) and cyclosporine withdrawal (CNI-free) or continue cyclosporine with standard EC-MPS (CNI). The primary endpoint was progression of graft fibrosis (interstitial fibrosis/tubular atrophy [IF/TA] grade increase ≥1 between months 3-12) in EMT+ patients. 194 patients were randomized (96 CNI-free, 98 CNI); 153 (69 CNI-free, 84 CNI) were included in histological analyses. Fibrosis progression occurred in 46.2% (12/26) CNI-free EMT+ patients versus 51.6% (16/31) CNI EMT+ patients (p = 0.68). Biopsy-proven acute rejection (BPAR, including subclinical events) occurred in 25.0% and 5.1% of CNI-free and CNI patients, respectively (p < 0.001). In conclusion, early CNI withdrawal with everolimus initiation does not prevent interstitial fibrosis. Using this CNI-free protocol, in which everolimus exposure was relatively low and administered with half-dose EC-MPS, CNI-free patients were overwhelmingly under-immunosuppressed and experienced an increased risk of BPAR.

One hundred ninety-seven patients received anti-T-lymphocyte globulins Fresenius, mycophenolate mofetil and delayed cyclosporine, and were randomized to ≥6-month corticosteroids (+CS; n = 99) or no CS (−CS; n = 98). One- and five-year actual graft survival (censored for death) was 93.2% and 86.4% in the +CS group versus 94.9% and 89.8% in the −CS group (5-year follow-up, p = 0.487). Freedom from clinical rejection was 86.9% and 81.8% versus 74.5% and 74.5% (p = 0.144), respectively, at 1 and 5 years; 5-year freedom from biopsy-proven rejection was 88.9% versus 83.7% (p = 0.227). More late first rejections occurred in the +CS group. Significantly lower 5-year graft survival in patients experiencing rejection was observed for +CS (55.6% vs. 92.0%; p = 0.005) with 8/18 versus 2/25 graft losses. Renal function at 5 years was stable and comparable (median serum creatinine, 159 vs. 145 µmol/L; creatinine clearance, 53.5 vs. 56.6 mL/min). More +CS patients developed diabetes, dyslipidemia and malignancies. Rejections in −CS patients occurred early after transplantation and did not impair long-term renal function. In patients receiving CS, rejections occurred later and with a higher risk for subsequent graft failure. A similar and not inferior 5-year efficacy profile and a reduced morbidity were observed in CS-free patients compared to patients who received CS for at least 6 months.

Background Several studies found differences in tacrolimus whole blood trough levels (C0) or area-under-the curve (AUC) between the twice-daily (Tac-BID) and once-daily (Tac-OD) formulations given to kidney transplant recipients at equal doses. As C0 is widely used as a surrogate of the AUC for individual dose adjustment, this study investigated the correlation and proportionality between C0 and the 24h-AUC, depending on the formulation, time post-transplantation, pharmacogenetics traits and other individual characteristics. Methods 45 adult kidney transplant recipients were randomized to receive either Tac OD or Tac BID. On days 8 ± 1 (D8) and 90 ± 3 (month 3, M3), blood samples were collected over 24 h in both groups. Tacrolimus concentrations were determined using HPLC–MS/MS and common CYP3A5, CYP3A4 and ABCB1 genotypes characterized using allelic discrimination assays. Tacrolimus population pharmacokinetics was studied in the two patient groups using the Iterative Two Stage (ITS) technique, considering a one-compartment model with two gamma laws to describe the absorption phase. Bayesian estimation based on the C0, C1 h and C3 h concentrations was employed to estimate individual Tac AUC0-12h and AUC12-24h (for Tac BID), or AUC0–24h (for Tac OD). Multiple linear regression was used to evaluate the influence of Tac formulation, post-transplantation period, recipient gender, existing glucose metabolism disorders, and CYP3A5, CYP3A4 and ABCB1 genotypes on C0, AUC0–24h and the AUC-to-trough concentration ratios. Results The Full Analysis Set comprised 22 patients on Tac OD and 20 on Tac BID. Tac exposure indices as well as their time evolution were similar in the two groups. Multi-linear modeling analysis showed that the Tac dose was higher with Tac-OD than Tac-BID, on D8 than at M3 and in CYP3A5 expressors (p Conclusions This study confirms that the precisely timed 12h- or 24h-post-dose blood concentration (as opposed to the vaguely defined ‘trough level’) is a convenient surrogate of the 24h-AUC of tacrolimus for the two TAC formulations over the first 3 months post-transplantation. Still, for a given C24 h value, AUC0–24h was higher on D8 and in CYP3A5 expressors. Bayesian estimation of AUC0-12h for TAC BID and AUC0–24h for TAC OD is feasible using only 3 time points within the first 3 h, thus giving access to the actual overall exposure.

Our objective was to compare the outcomes of dual kidney transplanataion (DKT) to single kidney transplantation (SKT) performed with grafts from expanded criteria donors (ECD) in recipients ≥65 years, focusing on surgical complications. All kidney transplantations (KT) performed between 2006 and 2014 in our institution were analysed. DKT was indicated according to the criteria of the French national Agence de la Biomedecine. Thirty-nine DKT and 155 SKT were included, with a median follow-up of 36 and 26.5 months, respectively. The rate of early surgical revisions was not significantly higher after DKT (23.1% vs 15.5% (P = 0.2593)) but more venous graft thromboses (12.8% vs 3.2% (P = 0.02)) were reported. The glomerular filtration rate (GFR) 24 months after KT was significantly higher after DKT (45.0 ± 16.3 vs 39.8 ± 13.8 ml/min/1.73m2 ; P = 0.04) and allowed shorter waiting time without a significant increased risk of surgical revision, excepted for venous graft thrombosis, more frequent after DKT. Graft survivals were not significantly different and GFR was higher after DKT. DKT seems to remain an appropriate strategy to address the growing graft shortage in elderly patients.

Background. Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). Methods. Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, SCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). Results. Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). Conclusions. Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation.

BACKGROUND The predictive value of anti-M-type phospholipase A2 receptor (PLA2R1) autoantibodies for membranous nephropathy (MN) recurrence after renal transplantation remains controversial. METHODS Our aim was to monitor anti-PLA2R1 IgG4 activity using a sensitive enzyme-linked immunosorbent assay in 15 kidney transplant recipients with MN, and to test the correlation between antibody titres and MN recurrence. RESULTS Five patients never exhibited anti-PLA2R1 antibodies, and one of them relapsed. Ten patients (67%) had IgG4 anti-PLA2R1 antibodies at the time of transplantation and during follow-up. The presence of IgG4 anti-PLA2R1 antibodies at the time of kidney transplantation does not imply MN recurrence (P = 0.600, n = 15). However, a positive IgG4 anti-PLA2R1 activity during follow-up (>Month 6) was a significant risk factor for MN relapse (P = 0.0048, n = 10). Indeed, four patients had persistent IgG4 anti-PLA2R1 activity after transplantation and relapsed. Among them, one was successfully treated with rituximab. Another had persistently high IgG4 anti-PLA2R1 activity and exhibited a histological relapse but no proteinuria while on treatment with renin-angiotensin system inhibitors. In contrast, the six other patients who did not relapse exhibited a decrease of their IgG4 anti-PLA2R1 activity following transplant immunosuppression, including two with proteinuria due to biopsy-proven differential diagnoses. A weak transplant immunosuppressive regimen was also a risk factor of MN recurrence (P = 0.0048, n = 10). Indeed, the six patients who received both an induction therapy and a combined treatment with calcineurin inhibitors/mycophenolate exhibited a decrease of IgG4 anti-PLA2R1 activity and did not relapse, while the four patients who did not receive this strong immunosuppressive treatment association had persistently high IgG4 anti-PLA2R1 activity and relapsed. CONCLUSION The monitoring of IgG4 anti-PLA2R1 titres during follow-up helps to predict MN recurrence, and a strong immunosuppressive treatment of anti-PLA2R1 positive patients may prevent recurrence.

Resume Objectifs Evaluer l’exerese de l’uretere distale et de la collerette vesicale par voie ouverte ou endoscopique apres nephroureterectomies laparoscopiques (NUL) dans le traitement des tumeurs des voies urinaires superieures Patients et methodes Il s’agissait d’une etude retrospective de patients ayant une NUL entre 2004 et 2012 dans deux centres de reference. La resection de l’extremite distale de l’uretere et de la collerette vesicale etait realisee soit par laparotomie, soit par resection transuretrale de l’orifice ureteral (RTUOU). Les complications, les resultats fonctionnels et oncologiques etaient analyses dans le suivi. Resultats Sur 29 patients traites par NUL, 16 patients ont eu une excision ouverte (EO) et 13, une RTUOU. L’âge median etait superieur dans le groupe EO (66,5 ans [48–87]). La duree d’intervention etait inferieure pour l’EO (180 min vs 240 min [ p p p = 0,03]) et d’avantage de haut grade (81,3 % vs 38,5 % [ p = 0,026]). Le taux de survie specifique a 5 ans, toutes techniques confondues, etait de 63,72 %, sans qu’aucune distinction entre les deux groupes n’ait pu etre rapportee sur le plan oncologique. Conclusion La RTUOU entrainait une diminution du sejour hospitalier mais etait associee a une duree d’intervention prolongee, par rapport a l’OE, sans generer de difference de complications. Les resultats oncologiques ne mettaient pas en evidence de difference significative entre les techniques ; mais un plus long suivi est necessaire pour confirmer ces resultats. Niveau de preuve 4.

Introduction Les etudes comparant l’efficacite des machines de perfusion hypothermiques (MP) par rapport a la conservation statique (CS) se fondent sur des criteres a court terme, en particulier le retard au demarrage [1] . Notre etude a pour but d’identifier un profil de donneur qui maximiserait le benefice de la MP en terme de survie du patient et son greffon a moyen terme. Patients/Materiels et methodes Il s’agit d’une etude de cohorte prospective multicentrique de patients transplantes renaux pour la premiere ou la seconde fois entre 2010 et 2017 dans 8 centres hospitaliers francais. Notre critere de jugement principal est la survie patient-greffon. Notre cohorte (n = 3154) a ete divisee aleatoirement en deux echantillons, l’un d’apprentissage (n = 2057) et l’autre de validation (n = 1097). Les interactions entre l’utilisation des MP et les caracteristiques des donneurs ont ete testees sur la cohorte d’apprentissage par un modele de Cox puis validees la cohorte independante. Observation/Resultats Dans l’echantillon d’apprentissage, la mediane de suivi etait de 708 jours (0 a 7,25 ans) avec 232 pertes de greffon ou de deces. Dans le sous-groupe MP (n = 508), l’âge moyen des receveurs et des donneurs etait respectivement de 61 et 65 ans contre 52 et 53 ans dans le groupe CS (p Discussion La MP a montre un effet benefique dans la prevention du retard de fonctionnement du greffon avec une augmentation significative de la survie du greffon dans une grande etude randomisee [1] . Nos resultats suggerent que, dans une utilisation de routine, la MP ne modifie pas le pronostic a moyen terme sur la survie greffon-patient. Nous n’avons pas pu montrer un effet plus prononce de la MP pour un profil de donneur particulier. Conclusion Nous n’avons pas pu mettre en evidence de difference de survie par l’emploi des MP ni identifier de profil de donneur pouvant en beneficier.

Introduction Chez les sujets a faible risque immunologique, la Thymoglobuline (ATG) et le Basiliximab (BSX) conduisent a des taux de rejet similaires. L’ATG ameliore le retard de fonction du greffon (DGF) et evite l’utilisation de corticoides ; mais peut induire un surrisque infectieux et neoplasique. La balance benefice risque chez le sujet âge est mal definie, nous avons donc compare le traitement d’induction chez les transplantes renaux âges a faible risque immunologique. Methodes Nous avons conduit une etude de cohorte multicentrique chez les sujets ≥ 65 ans non immunises ayant recu une 1e greffe renale entre 2010 et 2017 et une induction par ATG ou BSX. Le critere de jugement principal etait la survie patient/greffon, les criteres secondaires etaient les probabilites d’infection, cancer, rejet, diabete post-transplantation (DPT) et complications cardiaques ; la fonction renale (eDFG) et la survenue de DSA a 1 an ; ainsi que la DGF. Des modeles de Cox lineaires ou logistique etaient utilises selon la variable etudiee et les modeles etaient ajustes a l’aide de scores de propension. Resultats obtenus ou attendus Deux cents quatre patients (53,3 %) etaient inclus dans le groupe BSX et 179 (46,7 %) dans le groupe ATG. L’âge moyen etait respectivement de 71,0 et 70,5 ans. La survie patient/greffon a 3 ans etait de 74 % (IC 95 % = 68 % ; 84 %) dans le groupe ATG et 68 % (IC 95 % = 60 % ; 78 %) dans le groupe BSX, sans difference significative. La survenue de PTD etait significativement plus importante dans le groupe BSX (23 % vs. 15 %, p = 0,04) du a des taux residuels de tacrolimus plus eleves a 3 mois (9,48 vs. 7,30 ng/ml, p = 0,023). Il n’y avait pas de difference significative observee sur les autres criteres secondaires etudies ( Fig. 1 ). Conclusion Chez les sujets âges, l’ATG equivaut le BSX, et pourrait permettre de diminuer le tacrolimus, diminuant la survenue de PTD.

Resume Les molecules immunosuppressives utilisees pour reduire le conflit hote-greffon chez les patients transplantes creent un terrain favorable aux infections virales. Ces infections frequentes et diverses affectent l’efficacite globale des transplantations et compliquent serieusement le suivi des receveurs. Quelques molecules antivirales, actives en particulier contre les herpesvirus, permettent d’agir contre des infections qui sont frequentes chez le transplante, notamment l’infection a CMV. Cependant de nombreuses infections virales n’ont aucun traitement et l’usage des antiviraux actuels est limite par leur manque de specificite et leurs effets toxiques. La tendance actuelle est d’allonger la duree des traitements, ce qui favorise la selection de virus resistants et accroit les effets secondaires. L’immunosuppression provoquee chez les sujets transplantes affecte fortement l’activite antivirale qui est principalement assuree par les lymphocytes T. Pour pallier ce deficit lymphocytaire, une idee simple consiste a injecter des doses de lymphocytes T selectionnes et caracterises ex vivo pour leurs proprietes antivirales. Depuis le debut des annees 90, les approches de lymphotherapies adoptives se developpent activement dans les meilleurs centres de therapie cellulaire; les essais cliniques de phases I ou II totalisent a ce jour plusieurs centaines de patients inclus et les premiers essais de phase III sont en cours. Le mode de production des lymphocytes antiviraux peut s’operer selon des strategies differentes (amplification par culture ou tri-direct des lymphocytes antiviraux sanguins), toutefois toutes les etudes realisees etablissent de maniere non-ambigue, non seulement l’efficacite antivirale de ce type d’approches, mais egalement leur faisabilite et leur excellente tolerance. Dans le contexte du traitement des infections virales du sujet sous immunosuppresseur, nous illustrerons notamment ces propos en presentant le resultat de plusieurs essais cliniques qui ont ete realises ces dernieres annees pour prevenir ou traiter les infections a CMV, a EBV et a adenovirus chez le patient transplante.