Publications by authors named "Corinne Antoine"

46 Publications

Liver transplantation for critically ill cirrhotic patients: results from the French transplant registry.

Clin Res Hepatol Gastroenterol 2021 Oct 1:101817. Epub 2021 Oct 1.

Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

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: age > 50 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.
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http://dx.doi.org/10.1016/j.clinre.2021.101817DOI Listing
October 2021

Successful Reuse of Kidney Graft After Early Recurrence of Primary Focal and Segmental Glomerulosclerosis.

Am J Kidney Dis 2021 12 9;78(6):897-901. Epub 2021 Jun 9.

Departments of Nephrology, Dialysis, Transplantation, and Apheresis, Lille University, Regional and University Hospital Center of Lille, Lille, France.

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 1.2mg/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.
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http://dx.doi.org/10.1053/j.ajkd.2021.03.028DOI Listing
December 2021

Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society.

Transplantation 2021 05;105(5):945-951

Edinburgh Transplant Center, Royal Infirmary of Edinburgh, United Kingdom.

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.
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http://dx.doi.org/10.1097/TP.0000000000003729DOI Listing
May 2021

Impact of coronavirus disease 2019 on organ donation and transplantation in France.

Transpl Int 2021 01 10;34(1):204-206. Epub 2020 Nov 10.

Direction Prélèvement Greffe Organe - Tissus, Agence de la Biomédecine, La Plaine Saint-Denis, France.

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http://dx.doi.org/10.1111/tri.13769DOI Listing
January 2021

COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes.

J Am Soc Nephrol 2020 10 26;31(10):2413-2423. Epub 2020 Aug 26.

Kidney Transplant Department, Saint Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

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; =0.007), obesity (OR, 2.19; 95% CI, 1.19 to 4.05; =0.01), asthma and chronic pulmonary disease (OR, 3.09; 95% CI, 1.49 to 6.41; =0.002), and diabetes (OR, 3.33; 95% CI, 1.92 to 5.77; <0.001). The mortality rate related to COVID-19 disease was 1% in the overall study population and 24% in COVID-19-positive patients.

Conclusions: Patients with kidney transplants display a high risk of mortality. Non-White ethnicity and comorbidities such as obesity, diabetes, asthma, and chronic pulmonary disease were associated with higher risk of developing COVID-19 disease. It is imperative that policy makers urgently ensure the integration of such risk factors on response operations against COVID-19.
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http://dx.doi.org/10.1681/ASN.2020050639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609004PMC
October 2020

Should we use liver grafts repeatedly refused by other transplant teams?

JHEP Rep 2020 Aug 4;2(4):100118. Epub 2020 May 4.

Centre Hépato-Biliaire, Hôpital Paul Brousse, APHP, Villejuif, France.

Background & Aims: In France, liver grafts that have been refused at least 5 times can be "rescued" and allocated to a centre which chooses a recipient from its own waiting list, outside the patient-based allocation framework. We explored whether these "rescued" grafts were associated with worse graft/patient survival, as well as assessing their effect on survival benefit.

Methods: Among 7,895 candidates, 5,218 were transplanted between 2009 and 2014 (336 centre-allocated). We compared recipient/graft survival between patient allocation and centre allocation, considering a selection bias and the distribution of centre-allocation recipients among the transplant teams. We used a propensity score approach and a weighted Cox model using the inverse probability of treatment weighting method. We also explored the survival benefit associated with centre-allocation grafts.

Results: There was a significantly higher risk of graft loss/death in the centre allocation group compared to the patient allocation group (hazard ratio 1.13; 95% CI 1.05-1.22). However, this difference was no longer significant for teams that performed more than 7% of the centre-allocation transplantations. Moreover, receiving a centre-allocation graft, compared to remaining on the waiting list and possibly later receiving a patient-allocation graft, did not convey a poorer survival benefit (hazard ratio 0.80; 95% CI 0.60-1.08).

Conclusions: In centres which transplanted most of the centre-allocation grafts, using grafts repeatedly refused for top-listed candidates was not detrimental. Given the organ shortage, our findings should encourage policy makers to restrict centre-allocation grafts to targeted centres.

Lay Summary: "Centre allocation" (CA) made it possible to save 6 out of 100 available liver grafts that had been refused at least 5 times for use in the top-listed candidates on the national waiting list. In this series, the largest on this topic, we showed that, in centres which transplanted most of the CA grafts, using grafts repeatedly refused for top-listed candidates did not appear to be detrimental. In the context of organ shortage, our results, which could be of interest for any country using this CA strategy, should encourage policy makers to reassess some aspects of graft allocation by restricting CA grafts to targeted centres, fostering the "best" matching between grafts and candidates on the waiting list.
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http://dx.doi.org/10.1016/j.jhepr.2020.100118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364172PMC
August 2020

Removing administrative boundaries using a gravity model for a national liver allocation system.

Am J Transplant 2021 03 1;21(3):1080-1091. Epub 2020 Oct 1.

Agence de la Biomédecine, Medical and Scientific Department, Simulation and Health Geography Units, Saint-Denis La Plaine cedex, France.

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.
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http://dx.doi.org/10.1111/ajt.16214DOI Listing
March 2021

Favorable Outcomes of Liver Transplantation from Controlled Circulatory Death Donors Using Normothermic Regional Perfusion Compared to Brain Death Donors.

Transplantation 2020 09;104(9):1943-1951

Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Pitié-Salpêtrière, AP HP, Sorbonne Université, Paris, France.

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.
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http://dx.doi.org/10.1097/TP.0000000000003372DOI Listing
September 2020

Liver Transplantation From Controlled Donors After Circulatory Death Using Normothermic Regional Perfusion: An Initial French Experience.

Liver Transpl 2020 11 20;26(11):1516-1521. Epub 2020 Oct 20.

Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Centre Hospitalier Universitaire Pitié-Salpetriere, Paris, France.

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.
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http://dx.doi.org/10.1002/lt.25818DOI Listing
November 2020

Matching Graft Quality to Recipient's Disease Severity Based on the Survival Benefit in Liver Transplantation.

Sci Rep 2020 03 5;10(1):4111. Epub 2020 Mar 5.

University of Montpellier, Department of Biostatistics, UPRES EA2415, Clinical Reasearch University Institute, Montpellier, France.

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.
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http://dx.doi.org/10.1038/s41598-020-60973-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057972PMC
March 2020

Impact of the new MELD-based allocation system on waiting list and post-transplant survival - a cohort analysis using the French national CRISTAL database.

Transpl Int 2019 May 10. Epub 2019 May 10.

Inserm, UMR995 - LIRIC, Lille, France Univ Lille, UMR995 - LIRIC, Lille, France CHRU Lille, Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital HuriezLille, France.

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 MELD<35 (74.8% vs 86.3%; p<0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD>35, 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%; p<0.01). The implementation of the MELD-based allocation system has led to transplant sicker patients with no impact on waitlist and post-transplant survivals. Nevertheless, selection of patients with MELD>35 should be completed to allow safe transplantation. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/tri.13448DOI Listing
May 2019

Kidney Transplant From Uncontrolled Donation After Circulatory Death: Contribution of Normothermic Regional Perfusion.

Transplantation 2020 01;104(1):130-136

Hôpital de la Pitié Salpêtrière, Urologie, Paris, France.

Background: The French uncontrolled donors after circulatory death (DCD) protocol restricts donor age to <55 years, no-flow time to <30 minutes, and functional warm ischemia time to <150 minutes. In situ kidney perfusion can be performed at either 4°C (in situ cooling [ISC]) or 33-36°C (normothermic regional perfusion [NRP]). Hypothermic machine perfusion is systematically used. Only nonimmunized first transplant recipients were eligible. To improve the management of uncontrolled DCD, we tried to identify factors predictive of outcome.

Methods: We identified all kidney transplants from uncontrolled DCD between 2007 and 2014 from the French Transplant Registry. Risk factors for primary nonfunction (PNF; n = 37) and poor renal function (estimated glomerular filtration rate < 30 mL/min or graft loss at 1 y, n = 66) were analyzed by using a multivariate logistic model.

Results: This study analyzed 499 kidney transplantations, 50% of which were performed with NRP. Mean functional warm ischemia time was 135 minutes. Mean cold ischemia time was 14 hours. The principal PNF risk factor was young donor age (odds ratio [OR] = 0.95; P = 0.002). A sensitivity analysis showed a higher risk of PNF with ISC than with NRP (OR = 4.5; P = 0.015). Risk factors for poor renal function were donor body mass index (OR = 1.2; P < 0.001) and ISC versus NRP. Univariate analysis of uncontrolled DCD-specific risk factors showed no-flow time, functional warm time, and cold ischemia time did not affect the risk of PNF or poor renal function.

Conclusions: Uncontrolled DCD kidneys are an additional source of valuable transplants. NRP appears to decrease graft failure by restoring oxygenated blood as the first step of preconditioning.
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http://dx.doi.org/10.1097/TP.0000000000002753DOI Listing
January 2020

Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation.

J Hepatol 2019 05 14;70(5):831-838. Epub 2019 Mar 14.

CHRU de Lille, France, Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, France. Electronic address:

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 <0.0001). Ten-year kidney graft survival was lower in HCV-infected (50.6%) than in HBV-infected (62.3%, p <0.0001) or non-infected kidney transplant recipients (64.7%, p <0.0001). A random analysis of the medical records of 184 patients with HBV and 504 patients with HCV showed a control of viral replication in 94% and 35% of cases, respectively. Ten-year patient and graft survival in patients with detectable HCV RNA was lower than in their matching controls. Conversely, patients with HCV and undetectable HCV RNA had higher 10-year survival than their matched controls without significant differences in graft survival.

Conclusions: Chronic HBV infection does not impact 10-year patient and kidney graft survival thanks to control of viral replication with nucleos(t)ide analogues. In kidney transplant recipients infected with HCV, patients with detectable RNA had worse outcomes, whereas the outcomes of those with undetectable RNA were at least as good as non-infected patients. Thus, direct-acting antivirals should be systematically offered to HCV-infected patients.

Lay Summary: Previously, infections with hepatitis B or hepatitis C virus led to poor outcomes in kidney transplant recipients. However, the outcomes of kidney transplants in patients with viral suppression are as good as those for kidney transplants in non-infected patients. Antiviral therapy should be systematically proposed to hepatitis B and/or hepatitis C-infected kidney transplant recipients or candidates to prevent the deleterious hepatic and extrahepatic impact of chronic viral replication. Recent access to direct-acting antivirals in patients with hepatitis C virus and renal dysfunction provides exciting new opportunities.
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http://dx.doi.org/10.1016/j.jhep.2018.12.036DOI Listing
May 2019

Evaluation of outcomes in renal transplantation with hypothermic machine perfusion for the preservation of kidneys from expanded criteria donors.

Clin Transplant 2019 05 10;33(5):e13536. Epub 2019 Apr 10.

Agence de la Biomédecine, Direction Prélèvement Greffe Organes-Tissus, Saint-Denis La Plaine, France.

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.
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http://dx.doi.org/10.1111/ctr.13536DOI Listing
May 2019

Liver Transplantation in France.

Liver Transpl 2019 05 1;25(5):763-770. Epub 2019 Apr 1.

Hepato-Biliary, Liver Transplantation, and Pancreatic Surgery, Hospital Beaujon, Clichy, France.

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 Biomédecine). 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.
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http://dx.doi.org/10.1002/lt.25419DOI Listing
May 2019

Author Correction: A Donor Quality Index for liver transplantation: development, internal and external validation.

Sci Rep 2018 Oct 5;8(1):15109. Epub 2018 Oct 5.

Department of Biostatistics, UPRES EA2415, Clinical Research University Institute, Montpellier, France.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-30974-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172196PMC
October 2018

A Donor Quality Index for liver transplantation: development, internal and external validation.

Sci Rep 2018 06 29;8(1):9871. Epub 2018 Jun 29.

Department of Biostatistics, UPRES EA2415, Clinical Research University Institute, Montpellier, France.

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.
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http://dx.doi.org/10.1038/s41598-018-27960-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026153PMC
June 2018

[Kidney transplantation from Maastricht III donors after circulatory death, overview of the situation in France].

Soins 2018 Jun;63(826):36-38

Direction médicale et scientifique, Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La Plaine cedex, France.

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.
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http://dx.doi.org/10.1016/j.soin.2018.04.010DOI Listing
June 2018

Relationships Between Self-Injurious Behaviors, Pain Reactivity, and β-Endorphin in Children and Adolescents With Autism.

J Clin Psychiatry 2018 Mar/Apr;79(2)

Center of Excellence for Pervasive Developmental Disorders of the University of Montreal (CETEDUM), Rivières-des-Prairies Hospital, Montreal, Quebec, Canada.

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.
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http://dx.doi.org/10.4088/JCP.16m10889DOI Listing
June 2019

Impact of transplant accessibility for sensitized patients by avoiding unacceptable antigens.

Liver Transpl 2017 07;23(7):880-886

Department of Nephrology and Organ Transplantation, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

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.
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http://dx.doi.org/10.1002/lt.24781DOI Listing
July 2017

Organ Transplantation in France.

Transplantation 2017 03;101(3):445-448

1 Agence de la Biomédecine, Saint Denis, France. 2 Service de Nephrology-Transplantation, Hôpital Necker, Assistance Publique-Hôpitaux de Paris & Faculté Paris Descartes Sorbonne Paris Cité, Paris, France.

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http://dx.doi.org/10.1097/TP.0000000000001510DOI Listing
March 2017

Early Identification of Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and Consideration for Organ Donation.

Ann Intern Med 2016 Dec 13;165(11):770-778. Epub 2016 Sep 13.

From Paris Cardiovascular Research Center, Hôpital Necker-Enfants Malades, Hôpital Cochin, Université Paris Descartes-Sorbonne Paris Cité, Hôpital Saint-Louis, Université Paris Diderot - Paris VII, Hôpital Européen Georges Pompidou, and Paris Fire Brigade, Paris, France; Hôpital Avicenne, Université Paris 13, Bobigny, France; and Public Health-Seattle & King County and University of Washington, Seattle, Washington.

Background: In patients with out-of-hospital cardiac arrest (OHCA), care requirements can conflict with the need to promptly focus efforts on organ donation in patients who are pronounced dead.

Objective: To evaluate objective criteria for identifying patients with OHCA with no chance of survival during the first minutes of cardiopulmonary resuscitation to enable prompt orientation toward organ donation.

Design: Retrospective assessment using OHCA data from 2 registries and 1 trial.

Setting: France (Paris Sudden Death Expertise Center [SDEC] prospective cohort [2011 to 2014] and PRESENCE multicenter cluster randomized trial [ClinicalTrials.gov: NCT01009606] [2009 to 2011]) and the United States (King County, Washington, prospective cohort [2006 to 2011]).

Patients: 1771 patients from the Paris SDEC 1-year cohort (2011 to 2012) and 5192 from the validation cohorts.

Measurements: Evaluation of 3 objective criteria (OHCA not witnessed by emergency medical services personnel, nonshockable initial cardiac rhythm, and no return of spontaneous circulation before receipt of a third 1-mg dose of epinephrine), survival rate at hospital discharge among patients meeting these criteria, performance of the criteria, and number of patients eligible for organ donation.

Results: In the Paris SDEC 1-year cohort, the survival rate among the 772 patients with OHCA who met the objective criteria was 0% (95% CI, 0.0% to 0.5%), with a specificity of 100% (CI, 97% to 100%) and a positive predictive value of 100% (CI, 99% to 100%). These results were verified in the validation cohorts. Ninety-five (12%) patients in the Paris SDEC 1-year cohort may have been eligible for organ donation.

Limitation: Several patients had unknown outcomes.

Conclusion: Three objective criteria enable the early identification of patients with OHCA with essentially no chance of survival and may help in decision making about the organ donation process.

Primary Funding Source: French Ministry of Health.
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http://dx.doi.org/10.7326/M16-0402DOI Listing
December 2016

[New conditions for organ donation in France].

Soins 2016 Sep;61(808):26-31

Agence de la biomédecine, 1, avenue du Stade-de-France, 93212 Saint-Denis-La Plaine cedex, France.

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.
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http://dx.doi.org/10.1016/j.soin.2016.06.016DOI Listing
September 2016

Excellent long-term outcome of renal transplantation in cystinosis patients.

Orphanet J Rare Dis 2015 Jul 25;10:90. Epub 2015 Jul 25.

Service de Néphrologie-Transplantation, Hôpital Necker, 149 rue de Sèvres, 75015, Paris, France.

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.
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http://dx.doi.org/10.1186/s13023-015-0307-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515017PMC
July 2015

Kidney allograft fibrosis after transplantation from uncontrolled circulatory death donors.

Transplantation 2015 Feb;99(2):409-15

1 Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 2 Department of Pathology, Georges Pompidou European Hospital, Paris, France. 3 Biostatistics Unit, Paris Cardiovascular Research Centre, L'Université Paris Descartes, Paris, France. 4 Surgical Intensive Care Unit, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 5 Department of Pathology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 6 Department of Urology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 7 Department of Kidney Transplantation, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. † Deceased.

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.
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http://dx.doi.org/10.1097/TP.0000000000000228DOI Listing
February 2015

Glomerular filtration rate equations for liver-kidney transplantation in patients with cirrhosis: validation of current recommendations.

Hepatology 2014 Apr 3;59(4):1514-21. Epub 2014 Mar 3.

Department of Hepatology, Liver Intensive Care Unit and Transplantation, Hospital Beaujon, Clichy, France; INSERM U773, CRB3, University Denis Diderot Paris 7, Paris, France.

Unlabelled: 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 m(2), 15 patients (7%) had estimated GFR (eGFR) ≤40 mL/min/1.73 m(2) 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 m(2). However, the MDRD-6 equation also tended to underestimate renal function in a subgroup of patients with true GFR >30 mL/min/1.73 m(2), with a potential risk of unnecessary kidney transplantation if applying current U.S. recommendations for SLKT.
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http://dx.doi.org/10.1002/hep.26704DOI Listing
April 2014

Kidney graft dysfunction in simultaneous pancreas-kidney recipients after pancreas failure: analysis of early and late protocol biopsies.

Clin Transplant 2013 May-Jun;27(3):E249-55. Epub 2013 Feb 13.

Service de Néphrologie et Transplantation, Hôpital Saint-Louis, Paris, France.

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.
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http://dx.doi.org/10.1111/ctr.12095DOI Listing
January 2014

Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: effects on long-term renal function after liver transplantation.

J Hepatol 2012 Sep 18;57(3):572-6. Epub 2012 May 18.

Liver Transplant Unit, Hôpital Saint-Antoine, Assistance Publique-Hopitaux de Paris and Université Paris-Descartes, Paris, France.

Background & Aims: The incidence of organic renal lesions in patients with end-stage liver disease is unknown. The goal of this study was to make a prospective evaluation of renal histological lesions in a group of unselected patients awaiting liver transplantation.

Methods: Sixty cirrhotic patients underwent a renal biopsy via the transjugular route. The potential effect of renal lesions on renal function was evaluated five years after transplantation.

Results: The yield of biopsies enabling satisfactory analysis was 77%, and no major complications occurred. Proteinuria>0.5 g/day was observed in only 8.7% of these patients, microscopic haematuria in 4.3%, creatinine levels>133 mmol/L (1.5mg/dl) in 10.9%, and Modification of the Diet in Renal Disease (MDRD) clearance<60 ml/min in 13.0%. Twenty-five patients (55.3%) had a morphological diagnosis of renal disease, 15 displayed IgA nephropathy and immunofluorescence testing showed that 12 had specific diabetic linear staining for IgG and albumin, of whom seven had associated histological lesions of diabetic nephropathy. Five years after liver transplantation, renal function had significantly deteriorated more in patients with initial diabetic lesions than in those with normal histology or IgA nephropathy alone.

Conclusions: In patients with end-stage liver disease, IgA nephropathy and diabetic lesions were frequently found despite the absence of renal impairment and/or urinalysis anomalies. Our results strongly suggest that severe renal failure develops preferentially in liver transplant recipients with diabetes or carbohydrate intolerance, and that pre-existing arterial lesions may favour the nephrotoxicity of calcineurin inhibitors. Diabetes prior to transplantation needs to be strictly managed and requires a renal sparing immunosuppressive regimen after transplantation.
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http://dx.doi.org/10.1016/j.jhep.2012.04.028DOI Listing
September 2012

Preliminary results of transplantation with kidneys donated after cardiocirculatory determination of death: a French single-centre experience.

Nephrol Dial Transplant 2012 Jun 20;27(6):2583-7. Epub 2011 Dec 20.

Nephrology and Transplantation, Saint Louis Hospital, Assistance Publique - Hôpitaux de Paris.

Background: Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been re-introduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys.

Methods: Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation.

Results: From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 ± 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsy-proven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate ( Modification of Diet in Renal Disease formula) was 48 ± 16 mL/min/1.73 m(2) at 1 year and 48 ± 15 mL/min/1.73 m(2) at the last follow-up.

Conclusions: DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.
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http://dx.doi.org/10.1093/ndt/gfr709DOI Listing
June 2012
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