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International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Controlled donation after circulatory death (cDCD) is used for "extended criteria" donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12-1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time18 h, 1.57; 95% CI 1.20-2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31-2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.

Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.

A national program of controlled donation after circulatory death (cDCD) began in France in 2014 involving the use of a standardized national protocol that involves the systematic use of normothermic regional perfusion (NRP). In this article, we describe in detail the French cDCD program. Between January 1, 2015, and December 31, 2018, 225 livers were offered for donation, resulting in 123 cDCD liver transplantations (LTs). The overall 90-day graft survival rate was 93.1% (95% confidence interval [CI], 85.9%-96.6%). A total of 21 of 123 LTs (17%) did not adhere strictly to the national protocol. The 1-year graft survival was significantly lower in the group deviating from the national protocol compared with those patients following the national protocol: 68.4% (95% CI, 42.8%-84.4%) versus 94.8% (95% CI, 86.5%-98.0%; P < 0.01). There were 14 patients who died, including 2 after primary 2 after primary non function, and 10 related to liver cancer recurrence. Only 1 case of ischemic cholangiopathy was observed at month 18 in this series, and the patient underwent a successful retransplant. During the first 4 years, excellent LT results were observed where the national protocol was followed. Systematic use of NRP limits liver damage induced by warm ischemia and provides excellent cDCD organs for transplant.

BACKGROUND: COVID-19 has been associated with high morbidity and mortality in kidney transplant recipients. However, risk factors for COVID-19 disease in patients with kidney transplants remain poorly defined. METHODS: We enrolled patients who underwent kidney transplantation and were actively followed up in two hospitals in Paris on March 1st, 2020. Patients were screened for baseline and transplant characteristics, functional parameters, comorbidities, and immunosuppressive therapies. COVID-19 disease was assessed. Patients were followed up during the pandemic until April 30th, 2020 by the COVID-19 SLS KT survey program, including teleconsulting, at-home monitoring for patients with COVID-19, and a dedicated phone hotline platform. RESULTS: Among 1216 patients with kidney transplants enrolled, 66 (5%) patients were identified with COVID-19 disease, which is higher than the incidence observed in the general population in France (0.3%). Their mean age was 56.4±12.5 years, and 37 (56%) patients were men. The following factors were independently associated with COVID-19 disease: non-White ethnicity (adjusted odds ratio [OR], 2.17; 95% confidence interval [95% CI], 1.23 to 3.78; P=0.007), obesity (OR, 2.19; 95% CI, 1.19 to 4.05; P=0.01), asthma and chronic pulmonary disease (OR, 3.09; 95% CI, 1.49 to 6.41; P=0.002), and diabetes (OR, 3.33; 95% CI, 1.92 to 5.77; P

Persistent shortage and heterogeneous quality of liver grafts encourages the optimization of donor-recipient matching in liver transplantation (LT). We explored whether or not there was a survival benefit (SB) of LT according to the quality of grafts assessed by the Donor Quality Index (DQI) and recipients’ disease severity, using the Model for End-Stage Liver Disease (MELD) in 8387 French patients wait-listed between 2009 and 2014. SB associated with LT was estimated using the sequential stratification method in different categories of MELD and DQI. For each transplantation, a stratum was created that matched one transplanted patient with all eligible control candidates. Strata were thereafter combined, and a stratified Cox model, adjusted for covariates, was fitted in order to estimate hazard ratios that qualified the SB according to each MELD and DQI sub-group. A significant SB was observed for all MELD and DQI sub-groups, with the exception of high MELD patients transplanted with “high-risk” grafts. More specifically, in decompensated-cirrhosis patients, “high-risk” grafts did not appear to be detrimental in medium MELD patients. Interestingly, in hepatocellular-carcinoma (HCC) patients, a significant SB was found for all MELD-DQI combinations. For MELD exceptions no SB was found. In terms of SB, “low-risk” grafts appeared appropriate for most severe patients (MELD > 30). Conversely, low/medium MELD and HCC patients presented an SB while allocated “high-risk” grafts. Thus, SB based matching rules for LT candidates might improve the survival of the LT population as a whole.

International audience; Background & aims: Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status.Methods: Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively.Results: Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p

This study describes the population of cirrhotic patients who were transplanted from the ICU in France, identifying pre-transplant risk factors of post-transplant mortality and describing geographic variations in ICU transplant activity. Cirrhotic patients transplanted between 2008 and 2018 were included through the national transplant registry. The demographic, clinical and biological characteristics of the patients transplanted from the ICU were compared to cirrhotic patients who were transplanted from home or from the hospital. Risk factors of post-transplant one-year mortality were identified in uni- and multivariable analysis within the population transplanted from the ICU. Funnel plots were used to illustrate center-specific differences in ICU transplant activity. 1,047 cirrhotic patients were transplanted from the ICU during the study period. While the national rate of transplants performed from the ICU was 14.3% the absolute number and the rate of cirrhotic patients transplanted from the ICU varied significantly from one center to another, ranging from 6.6% to 22.8% (p 0.05). Three recipient-associated independent risk factors one-year post-LT mortality were identified in the population transplanted from the ICU: age50 years (HR 1.65, 95%CI 1.16-2.36), p = 0.005), diabetes (HR 1.46, 95%CI 1.07-1.98, p = 0.02) and intubation (HR2.12, 95%CI 1.62-2.78), p 0.001). Donor age was also independently associated with mortality (HR 1.01, 95%CI 1.01-1.02, p 0.001). Funnel plots showed significant differences in the proportion of patients transplanted from the ICU and the distribution of risk factors across French transplant centers, especially the inclination to transplant intubated patients. This study underlines the increased post-transplant mortality among cirrhotic patients transplanted from the ICU. It identifies four clinically pertinent independent risk factors associated with post-transplant mortality in this specific sub-group of transplant candidates. Finally, it illustrates how diverse the landscape of liver transplantation for critically ill cirrhotic patients is across a single country, despite a unified allocation algorithm.

With 187 919 cases and 30 265 deaths by July 31, 2020, France was severely affected by the COVID-19 pandemic, and the two-month confinement that began in mid-March. Although donor-to-recipient transmission and increased recipient mortality had been suggested by then, transplant-specific data were scarce [1-6]. The French transplant agency (ABM), acting with the public health council and scientific societies, recommended prophylactic measures, authorising procurement only for donors with negative SARS-CoV-2 screening in the 24 hours before procurement, no COVID-specific lung abnormality on CT scan and no clinical symptoms of or exposure to it in the previous 28 days. Each recipient's transplantation risks and benefits were reassessed in this context. Kidney, intestinal, pancreatic, islet cell and tissue transplantations were temporarily suspended, except for paediatric grafts and combined transplants.

In 2015, France authorised controlled donation after circulatory death (cDCD) according to a nationally approved protocol. The aim of this study is to provide an overview from the perspective of critical care specialists of cDCD. The primary objective is to assess how the organ donation procedure affects the withdrawal of life-sustaining therapies (WLST) process. The secondary objective is to assess the impact of cDCD donors' diagnoses on the whole process.This 2015-2019 prospective observational multicentre study evaluated the WLST process in all potential cDCD donors identified nationwide, comparing 2 different sets of subgroups: 1- those whose WLST began after organ donation was ruled out vs. while it was still under consideration; 2- those with a main diagnosis of post-anoxic brain injury (PABI) vs. primary brain injury (PBI) at the time of the WLST decision.The study analysed 908 potential cDCD donors. Organ donation remained under consideration at WLST initiation for 54.5% of them with longer intervals between their WLST decision and its initiation (2 [1-4] vs. 1 [1-2] days, P0.01). Overall, 60% had post-anoxic brain injury. Time from ICU admission to WLST decision was longer for primary brain injury donors (10 [4-21] vs. 6 [4-9] days, P0.01). Median time to death (agonal phase) was 15 [15-20] min.French cDCD donors are mostly related to post-anoxic brain injury. The organ donation process does not accelerate WLST decision but increases the interval between the WLST decision and its initiation.

Organ shortage leads to using non-optimal liver grafts. Thus, to determine the graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have been proposed. In a previous study we showed that neither could be validated on the French database. Our aim was then dedicated to propose an adaptive Donor Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in France between 2009 and 2013, with an external validation based on 1048 French LT performed in 2014. Using Cox models and three different methods of selection, we developed a new score and defined groups at risk. Model performance was assessed by means of three measures of discrimination corrected by the optimism using a bootstrap procedure. An external validation was also performed in order to evaluate its calibration and discrimination. Five donor covariates were retained: age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance, and liver type. Three groups at risk could be discriminated. The performances of the model were satisfactory after internal validation. Calibration and discrimination were preserved in the external validation dataset. The DQI exhibited good properties and is potentially adaptive as an aid for better guiding decision making for LT.

Recent data have confirmed the negative impact of preformed donor-specific antibodies (pDSAs) after liver transplantation (LT). In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in LT recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding pDSAs according to several mean fluorescence intensity (MFI) titer thresholds that have been previously reported to be relevant in LT. Among the 484 included LT candidates, 99 (20.5%) presented with anti-human leukocyte antibodies (HLAs). The predictive factors for anti-HLA sensitization were a history of previous kidney transplantation (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.30-1.9; P = 0.05), a history of previous LT (OR, 1.9; 95% CI, 1.6-2.1; P = 0.01), a history of blood transfusion (OR, 2.5; 95% CI, 2.2-4.1; P = 0.01), and a history of pregnancy (OR, 2.9; 95% CI, 2.4-3.3; P = 0.04). By applying a strategy of unacceptable mismatches for recipients with an antibody (Ab) MFI of > 5000, only 35 patients were affected (7% of the cohort), but 22 of these (63%) would have been considered incompatible with >50% of the donors. Using a MFI threshold of >10,000, only 16 patients were affected (1.4% of the cohort), but half of these would have been considered incompatible with >50% of the proposed donors. Considering only those with anti-class II Ab and a MFI >5000 and >10,000, respectively, 10/14 and 4/8 patients were considered incompatible with >50% of the donors. In conclusion, avoiding pDSAs affects a small but not negligible proportion of LT candidates. However, in these sensitive patients, avoiding pDSAs has the potential to significantly reduce the donor pool and, consequently, transplant accessibility. Liver Transplantation 23 880-886 2017 AASLD.

Geographic disparities emerged as an increasing issue in organ allocation policies. Because of the sequential and discrete geographical models used for allocation scores, artificial regional boundaries may impede the access of candidates with the greatest medical urgency to vital organs. This article describes a continuous geographical allocation model that provides accurate organ access by introducing a multiplicative interaction between the patient's condition and the distance to the graft by using a gravity model. Patients with the most urgent need will thus have access to organs from farther away, while those in less urgent need may only have access to organs geographically closer. Compared to the previous French liver allocation scheme, the gravity model precluded transplantations for candidates with a Model for End-Stage Liver Disease (MELD) ≤ 14 for decompensated cirrhosis from 10.3% to 0.6%. Death and delisting while on the waiting list at 1 year also decreased from 30.1% to 22.4% for MELD ≥ 35. Waiting list (cumulative hazard ratio (CHR) 0.84 after adjustment) and posttransplant survival improved significantly (hazard ratio = 0.83 after adjustment). This new liver allocation system provides more equitable access to liver transplants and an efficient and safe alternative to administrative boundaries for geographical models in organ allocation.

International audience; Background: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT.Methods: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT.Results: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68).Conclusions: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

Organ retrieval from deceased donors after controlled circulatory arrest improves access to kidney transplantation as a complement to brain dead donors. Authorised since 2014, they represent a real opportunity for patients awaiting a kidney transplant. The initial national results of the French protocol are encouraging.

The procurement of organs from donors after circulatory death is a reliable technique which gives satisfactory posttransplant results and also represents a potential source of additional organs. In order to meet the growing need for organ donations, the 'anticipated organ donation approach' procedure is currently receiving renewed interest with new conditions for its implementation in France.

International audience; Concerns related to equity and efficacy of our previous center-based allocation system have led us to introduce a patient-based allocation system called the "Liver Score" that incorporates the MELD score. The main objective of this study was to compare waitlist and post-transplant survivals before and after implementation of the "Liver Score" using the French transplant registry (period before: 2004-2006 and period after: 2007-2012). Patients transplanted during the second period were sicker and had a higher MELD. One-year waitlist survival (74% versus 76%; p=0.8) and one-year post-transplant survival (86.3% vs 85.7%; p=0.5) were similar between the 2 periods. Cirrhotic recipients with MELD>35 had lower one-year post-transplant survival compared to those with MELD35, patients presenting 2 or 3 risk factors (dialysis, intubation or infection) had a lower 1-year survival compared to those with none of these risk factors (61.2% vs 92%; p35 should be completed to allow safe transplantation. This article is protected by copyright. All rights reserved.

In France, the main indications for liver transplantation are hepatocellular carcinoma (HCC) and alcoholic cirrhosis. The number of candidates for decompensated hepatitis C virus-related cirrhosis has markedly decreased since the advent of direct-acting antiviral agents. Nonalcoholic steatohepatitis represents a lower proportion of candidates as compared with the United States. The main source of donors is donation after brain death, but the program of transplantation using donation after circulatory death is growing with excellent results. The deceased donation rate was 28.8 per million people in 2017, which has increased over the last few years. Adult-to-adult living donor liver transplantation has been almost completely abandoned. Donors are allocated on a national basis, and there is no longer local or regional priority. In patients with decompensated cirrhosis, prioritization is based on the Model for End-Stage Liver Disease (MELD) score. The distance between the donor and the recipient is taken into account according to an original gravity model. In patients with HCC, prioritization depends on the alfa-fetoprotein (AFP) score, the MELD score, and waiting time. Only patients with HCC tumor-node-metastasis ≥2 and AFP score ≤2 are eligible for the HCC score. A list of MELD exceptions, consisting of uncommon complications where mortality risk is not adequately predicted by the MELD score and conditions other than cirrhosis, has been established. MELD exceptions must be individually validated by a college of experts mandated by the French Regulatory Agency of Transplantation (Agence de la Biomedecine). The most common MELD exception is refractory ascites with a low MELD score. A major challenge is to reduce the rate of refusal of donation through information campaigns.

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.

Organ shortage leads to using non-optimal liver grafts. Thus, to determine the graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have been proposed. In a previous study we showed that neither could be validated on the French database. Our aim was then dedicated to propose an adaptive Donor Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in France between 2009 and 2013, with an external validation based on 1048 French LT performed in 2014. Using Cox models and three different methods of selection, we developed a new score and defined groups at risk. Model performance was assessed by means of three measures of discrimination corrected by the optimism using a bootstrap procedure. An external validation was also performed in order to evaluate its calibration and discrimination. Five donor covariates were retained: age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance, and liver type. Three groups at risk could be discriminated. The performances of the model were satisfactory after internal validation. Calibration and discrimination were preserved in the external validation dataset. The DQI exhibited good properties and is potentially adaptive as an aid for better guiding decision making for LT.

Organ retrieval from deceased donors after controlled circulatory arrest improves access to kidney transplantation as a complement to brain dead donors. Authorised since 2014, they represent a real opportunity for patients awaiting a kidney transplant. The initial national results of the French protocol are encouraging.

OBJECTIVE Autism and certain associated behaviors including self-injurious behaviors (SIB) and atypical pain reactivity have been hypothesized to result from excessive opioid activity. The objective of this study was to examine the relationships between SIB, pain reactivity, and β-endorphin levels in autism. METHODS Study participants were recruited between 2007 and 2012 from day care centers and included 74 children and adolescents diagnosed with autism (according to DSM-IV-TR, ICD-10, and CFTMEA) and intellectual disability. Behavioral pain reactivity and SIB were assessed in 3 observational situations (parents at home, 2 caregivers at day care center, a nurse and child psychiatrist during blood drawing) using validated quantitative and qualitative scales. Plasma β-endorphin concentrations were measured in 57 participants using 2 different immunoassay methods. RESULTS A high proportion of individuals with autism displayed SIB (50.0% and 70.3% according to parental and caregiver observation, respectively). The most frequent types of SIB were head banging and hand biting. An absence or decrease of overall behavioral pain reactivity was observed in 68.6% and 34.2% of individuals with autism according to parental and caregiver observation, respectively. Those individuals with hyporeactivity to daily life accidental painful stimuli displayed higher rates of self-biting (P < .01, parental evaluation). No significant correlations were observed between β-endorphin level and SIB or pain reactivity assessed in any of the 3 observational situations. CONCLUSIONS The absence of any observed relationships between β-endorphin level and SIB or pain reactivity and the conflicting results of prior opioid studies in autism tend to undermine support for the opioid theory of autism. New perspectives are discussed regarding the relationships found in this study between SIB and hyporeactivity to pain.

BACKGROUND: Existing data suggest that increased interstitial fibrosis may occur abnormally in renal transplants from donations after uncontrolled circulatory death (uDCD). METHODS: To evaluate the factors that are associated with the progression of fibrosis and its functional impact on renal grafts, we compared 76 uDCD recipients with 86 recipients of kidney donations after brain death at 1-year after transplantation. Groups were matched for donor age, rank of transplantation, and absence of human leukocyte antigen sensitization. Histology was performed on sequential biopsies in uDCD recipients. Associations between variables were analyzed using linear mixed models and univariate analyses. RESULTS: In the uDCD group, increased fibrosis was detected 3 months after transplantation compared to before implantation. After 1 year, interstitial fibrosis and tubular atrophy score was significantly greater (1.5±0.7 vs. 1.0±0.9; P=0.003) and estimated glomerular filtration rate (49.5±17.4 vs. 60.6±19.1 mL/min/1.73 m2; P=0.0003) was significantly lower in the uDCD group than in the donations after brain death group. No flow duration and donor age were significantly associated with accelerated fibrosis. Interstitial fibrosis and tubular atrophy score, interstitial inflammation score, and estimated glomerular filtration rate were significantly worse in uDCD patients with no flow longer than 10 min. CONCLUSION: Donations after uncontrolled circulatory death grafts show more fibrosis after transplantation. No flow duration is associated with accelerated fibrosis and should be considered during uDCD graft allocation.

Simultaneous liver and kidney transplantation (SLKT) remains the procedure of choice for patients with both endstage liver disease and kidney failure. Stringent guidelines are needed to avoid unnecessary kidney transplantation. A recent consensus meeting proposed criteria based on the Modified Diet in Renal Disease (MDRD)-6 equation to estimate glomerular filtration rate (GFR). The aims of this study were to compare GFR equations to true GFR in candidates for liver transplantation (LT) and to determine the impact of inaccuracies on the current guidelines for SLKT. Three hundred stable cirrhosis patients evaluated for LT were studied. All patients had iohexol clearance to measure GFR at evaluation under stable conditions. Measured GFR (mGFR) was compared to MDRD-4, MDRD-6, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. MDRD-6 was the most accurate equation to predict GFR. In the 290 patients with mGFR >30 mL/min/1.73 m2, 15 patients (7%) had estimated GFR (eGFR) ≤40 mL/min/1.73 m2 based on the MDRD-6 equation, defining “discordant” patients. Among them, two underwent SLKT and 13 underwent LT alone. None of those who survived more than 1 year after LT alone (n = 8) developed renal dysfunction thereafter. In multivariate analysis, discordant patients were older (P = 0.03) and had lower sodium level (P = 0.02). Conclusion: The MDRD-6 equation was superior to other equations at identifying cirrhosis patients with true GFR 30 mL/min/1.73 m2, with a potential risk of unnecessary kidney transplantation if applying current U.S. recommendations for SLKT. (Hepatology 2014;59:1514-1521)

Resume La greffe de foie s’est reellement developpee a partir des annees 1980. Ses indications se sont constamment elargies et elle represente aujourd’hui un traitement efficace de l’insuffisance hepatique terminale et de certaines tumeurs primitives hepatiques. Elle est soumise a un encadrement juridique commun aux autres greffes d’organes, qui definit precisement l’organisation des activites de prelevement et de greffe. Les questions reglementaires, concernant l’ethique medicale, sont liees essentiellement, d’une part, au choix des criteres determinant l’attribution des greffons hepatiques, avec un equilibre toujours difficile a atteindre entre les principes d’equite et d’efficacite, d’autre part, aux modalites de recours a la greffe a partir d’un donneur vivant.

We reported that current assignment of HLA-DQ is a barrier to organ allocation. Here we simulated the impact of incorporating HLA-DQ antigens and antibodies as A/B and αβ allelic variants, respectively, on calculated panel reactive antibody (cPRA) and probability of finding potential compatible donors (PCD). A cohort of 1224 donors and 2075 sensitized candidates was analyzed using HLA-DQαβ allelic (study) versus serologic (current practice) nomenclature. A significant (p

Background Kidney graft survival in simultaneous pancreas–kidney (SPK) recipients is known to decrease after pancreas graft failure. Methods Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed. Results Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence. Conclusion SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes.

The procurement of organs from donors after circulatory death is a reliable technique which gives satisfactory posttransplant results and also represents a potential source of additional organs. In order to meet the growing need for organ donations, the 'anticipated organ donation approach' procedure is currently receiving renewed interest with new conditions for its implementation in France.

La question du maintien du lien parent-enfant, en protection de l’enfance, genere de nombreuses reflexions tant de la part des chercheurs que des praticiens. Cette question est d’autant plus aigue qu’elle concerne des bebes pour lesquels il convient davantage de parler de construction du lien. La recherche (principalement anglo-saxonne) s’accorde pour mettre en avant l’effet benefique des visites parentales a l’enfant place, mais il existe des controverses tant sur la qualite methodologique des etudes existantes que sur l’interpretation de leurs resultats. Dans notre etude, nous proposons un suivi avant, pendant et apres la visite parentale des bebes. Nous mesurons le retrait relationnel (compris comme strategie de gestion des changements d’interactions) avant, pendant et apres la visite. Ces observations sont mises en parallele avec la sensibilite exprimee par le parent au cours de la visite et avec une evaluation des comportements de l’enfant dans la vie au sein du foyer. Les donnees recoltees permettent de faire l’hypothese de l’existence de trois profils de reaction des bebes. Certains enfants profitent des visites, d’autres vont moins bien en visite, mais recuperent de retour au foyer, enfin certains enfants ne semblent pas presenter de reactions. Les donnees suggerent aussi un effet de la sensibilite du parent, de la duree du placement, de la frequence des visites. Les conclusions sont discutees par rapport a la litterature existante et des pistes de recherches sont proposees en conclusion.

The utilization of sensitive techniques of detection of HLA antibodies to define and measure sensitization has greatly evolved in recent years. We present here an approach to minimize the risk of HLA antibodies in kidney transplantation based on the evaluation of graft accessibility of sensitized patients by calculated PRA (cPRA) and estimation of potential matched donors (PMD) using a national simulation software program. This study included all registered patients on our waiting list (WL) for deceased donor (DD) kidney transplants. All patients were screened by single-antigen flow bead (SAFB) techniques. Of the 502 registered patients, 174 (34.7%) were sensitized. Among these, 48.3% (84 pts) had a cPRA>85%. For 75.3% of sensitized patients (90 pts with cPRA≤85% and 41 pts with cPRA>85%), the flow of PMD was considered sufficient to allow a transplant avoiding all unacceptable antigens. The 41 patients with a cPRA>85% (48.8%) had a satisfactory donor flow in the framework of the national prioritization program for highly sensitized patients. Finally, 43 sensitized patients (24.7%) were deemed eligible for a strategy of higher immunological risk through desensitization protocols or transplantation against HLA-DSAs. This approach provides a logical and systematic strategy to rationalize the access of sensitized patients to kidney transplantation minimizing the risk of HLA antibodies.

Aucune etude n’a ete publiee a ce jour en langue francaise sur les besoins des proches accompagnant un sujet adulte souffrant d’un trouble du comportement alimentaire (TCA) et/ou d’une addiction. Dix-neuf proches de sujets adultes souffrant d’un TCA associe a une toxicomanie ou a un alcoolisme ont ete interviewes a l’aide d’un guide d’entretien semi-directif. Les protocoles, integralement enregistres et retranscrits mot a mot, ont fait l’objet d’une analyse thematique de contenu. Les resultats soulignent un triple besoin chez les proches : besoin en information sur les troubles et les traitements, besoin en guidance et besoin en soutien social et emotionnel. Cette etude incite a la prise de conscience, par les professionnels de la sante mentale, de la specificite et de l’urgence des besoins chez les proches confrontes au TCA et a l’addiction.

The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceased-donor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P = 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI >6000 had >100-fold higher risk for AMR than patients with MFI

L’objectif de cet article est de presenter un panorama des resultats des recherches, essentiellement qualitatives et anglophones, qui se sont penchees sur la question de l’impact du trouble du comportement alimentaire - TCA - sur les proches (non professional caregivers en langue anglaise). Les recherches recensees decrivent l’impact au quotidien du TCA sur la vie des proches : confrontation permanente aux symptomes, deterioration des relations avec le patient et stigmatisation. Elles rapportent aussi les impacts emotionnels et la detresse psychologique eprouvee par les proches, ainsi que les besoins generes par l’emergence des troubles : essentiellement besoins en information, en guidance et en soutien social et emotionnel. Elles soulignent l’importance de prendre en compte le vecu des proches dans le traitement du TCA et ouvrent des pistes nouvelles pour leur implication dans les protocoles de traitement.

Points essentiels Les regles anterieures de repartition des greffes laissaient une large place a la priorite locale, et la gestion finale a l’equipe, induisant de grandes disparites inter-regionales. Une etude prospective des deces et des retraits de liste d’attente pour aggravation de la maladie initiale (2003–2005) a permis de valider sur les donnees francaises l’utilisation du score MELD (Model for End-stage Liver Disease), qui permet de predire la survie spontanee des cirrhotiques a 3 mois, et qui est utilise aux Etats-Unis pour l’attribution des greffons hepatiques depuis 2002. La reflexion de l’Agence de biomedecine et des equipes de transplantation hepatique a conduit a mettre en place un score d’attribution des greffons hepatiques, a compter du 6 mars 2007. Ce score Foie tient compte du score MELD pour les cirrhoses, de la duree d’attente et du stade TNM pour les cancers, d’un score specifique pour les maladies metaboliques non cirrhotiques ainsi que pour les retransplantations electives, ainsi que d’aspects logistiques comme la distance entre le lieu de prelevement et celui de greffe. Un premier bilan a 5 mois indique que le score Foie permet de diminuer les deces et les retraits de liste pour aggravation, de diminuer le nombre de greffes « prematurees », d’accelerer l’acces a la greffe des malades les plus graves. Plusieurs questions restent en suspens : le score MELD et le score Foie peuvent etre ameliores, la variabilite du MELD liee aux methodes de dosage doit faire l’objet d’une normalisation entre laboratoires.

Resume En depit de l’augmentation significative de l’activite de prelevement et de greffe observee ces huit dernieres annees en France, la penurie s’accentue et les besoins en greffons demeurent tres superieurs a l’offre. Depuis 1968 et jusqu’a present, le prelevement a ete limite aux donneurs a cœur battant en etat de mort cerebrale. Les resultats de la greffe de reins, preleves sur donneurs a cœur arrete, se sont nettement ameliores et sont desormais comparables a ceux de la greffe renale a partir des donneurs en mort encephalique et cela grâce a une selection plus stricte des donneurs et des receveurs, le respect des delais d’ischemie chaude et froide et plusieurs innovations therapeutiques importantes. Le prelevement d’organes sur donneurs a cœur arrete a donc ete reconsidere sous l’angle de la faisabilite, des resultats et de leurs consequences ethiques et juridiques, dans le cadre exclusif d’un protocole medical edicte par l’agence de la biomedecine et d’une convention engageant le centre hospitalier pilote a respecter les termes du protocole. En regard des experiences etrangeres, ce programme est susceptible de diminuer la penurie d’organes qui penalise les nombreux patients en attente de transplantation.

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

Background Cystinosis is a rare lysosomal disorder leading to end stage renal disease in more than 90 % of patients before 20 years of age. Data about safety and efficiency of renal transplantation in patients with cystinosis is scarce. We evaluated long-term outcomes of renal transplantation in adult patients with cystinosis. Methods Data of renal transplantation (n = 31) in 30 adult patients with cystinosis in 5 French university transplant centers between 1980 and 2013 were retrospectively analyzed. A control cohort of 93 patients was matched for age, graft date, living/deceased donor status and transplant center. Results Median age at transplantation was 20.4 years (7–36.5). At transplantation, all patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had hypothyroidism. Graft survival was better in patients with cystinosis than in control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95 [0.02-0.61]). Specific complications of cystinosis occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus (PTDM) was not statistically different in cystinosis group compared to control group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no differences regarding calcineurin inhibitors and steroids treatments during follow-up. Conclusions Renal transplantation appears to be safe with excellent long-term outcomes in patients with cystinosis. These patients may receive standard immunosuppressive regimens with steroids and calcineurin inhibitors.

Resume Les regles de repartition des transplants renaux sont regulierement evaluees et modifiees en France, en fonction des avancees scientifiques, de l'evolution de la liste d'attente et des politiques de sante. Des modifications de ces regles ont ete effectuees en 2004 par l'Etablissement francais des Greffes, a l'initiative de la Commission de transplantation 1 de la Societe de Nephrologie, dans le but de diminuer le nombre des patients en attente ayant un acces difficile a la greffe en raison de leur statut immunogenetique (groupe ABO ou HLA rare, immunisation anti-HLA). Elles portent sur quatre points : 1/ une meilleure precision dans la definition de l'hyperimmunisation ; 2/ l'attribution, avec le programme dit « des antigenes permis », et non ; d'une nouvelle priorite aux patients hyperimmunises, pour qui les regles precedentes s'averaient insuffisantes ; 3/ la suppression de la priorite « full-match » aux patients non immunises ; 4/ l'attribution a certains patients immunises (anticorps anti-HLA = 5–80 %) ayant un acces difficile a la greffe, de priorites proches de celles des hyperimmunises. Le but de cet article est de presenter les nouvelles regles de repartition des greffons renaux et les raisons ayant conduit a ces modifications.