France has been a pioneer in organ transplantation with René Küss and Jean Hamburger who were among the first to perform renal transplants in the early 1950s.1
ORGAN TRANSPLANTATION IN FRANCE
France has a population of about 66 million (66.03 in 2013) with 116 organ transplant programs performing kidney (n = 44), liver (n = 21), heart (n = 25), lung (n = 12), intestine (n = 5), and pancreas transplants (n = 9). France also performs islet cell transplants (n = 11), vascularized composite allotransplants (n = 4), allogeneic-bone marrow transplants (n = 35). Pediatric transplants are performed in 17 centers (kidneys in 14, livers in 4, lungs in 1, and heart transplants in 6 centers). Two hundred twenty-two programs procure tissues stored at Tissue Banks.
THE “AGENCE DE LA BIOMÉDECINE”
Since 1996, the National Transplant Agency (called the Agence de la Biomédecine since 2005) has collected all data on potential and actual donors, procurement and transplantation characteristics and provides recipient follow-up information through a French national database called CRISTAL with the goal to (1) collect donor and recipient characteristics, (2) assure quality and safety of organ allocation while (3) supporting clinical research. In 2015, 5746 organ transplants were performed in France within 47 transplant centers at University hospitals (Figure 1). Annual transplant numbers in France have increased gradually (from 4.238 in 2005 to 5.746 in 2015, representing a 36% increase during the last 10 years). At the same time, waitlisted patients doubled (from 6.788 to 13.826). The majority of patients with end-stage-organ failure is listed actively with rates of 92%, 70%, 50%, and 60% for lung, cardiac, liver, and kidney transplants, respectively.2 In absolute numbers, France has had the highest transplant volume in Europe in 2014 and has been ranked third worldwide behind the United States and Brazil (Figure 2).
The “Agence de la Biomédecine” plays various roles during the organ donation, procurement, and transplantation process including, (1) managing the national refusal registry of individuals who do not wish to become donors; (2) administrating the national list of patients awaiting organ transplants; (3) developing a national database of volunteer donors for haematopoietic stem cell transplants; (4) organizing living donor committees; (5) developing allocation rules in cooperation with the transplant community; (6) coordinating organ procurement and organs allocation in France; (7) providing quality assessment and process improvement; and, finally, (8) representing a strong educational and outreach activity.
Priority is given to candidates with urgent medical needs for both renal and extrarenal organs and to candidates awaiting multiple organs including lung or heart transplants. Two algorithms permit access to the national priority list for highly sensitized patients awaiting renal transplant (sensitized patients with peak calculated panel reactive antibody ≥ 85%) including a specific acceptable mismatch protocol or, alternatively, 1 or less HLA-A, -B, -DR mismatch. In the absence of priorities, kidneys and livers are allocated to adult transplant candidates on the basis of allocation scores considering (1) blood type, donor/recipient distance, HLA matching, time spent in dialysis, time since registration, and age discrepancy between donor and recipient for kidney allocation3-5; and (2) for liver allocation, blood type, gravity model (spatial interaction between the distance and the recipient urgency status), Model for End-Stage Liver Disease, liver disease, and for hepatocellular carcinoma, tumor size, and α-fetoprotein.6,7 At this time, intestine, pancreas, heart, and lungs are mainly allocated according to urgency and local priority. Pediatric recipients have a national priority for pediatric organs that is extended to organs of young adults under specific conditions. The new patient-based liver allocation policy resulted in a significant decrease in deaths and too-sick patient delisting, without decline of posttransplant results while candidates are more severe (mean Model for End-Stage Live Disease at transplant higher) and donors are older. (Figure 3).
DONATION RATES AND ATTEMPTS TO IMPROVE DONOR CONVERSION
Deceased donation rates increased from 16.8 pmp in 2000 to 27,4 pmp in 2015 (+21% of recovered donors during the last 5 years). Organ donation in France is based on a presumed consent principle with the “Agence de la Biomédecine” providing an opportunity to register decisions opposed to donation. This National refusal registry is double-checked with every potential deceased donor before initiating donor work-up (approximately 140 000 individuals are currently listed with a registered refusal for donation). In 2015, 3579 eligible brain death donors had been reported with a conversion rate of 50% (1769 actual brain death donors with the procurement of at least 1 organ for transplantation). The main cause of death has been cerebrovascular stroke (56.3%), and the mean donor age has been 57.1 years. The mean number of organs recovered and transplanted/donor were 3.33 and 3.07, respectively, in 2015. The rate of organs recovered that had not been used for transplantation has been low (0.078/recovered organ in 2015, 2). Efficiency rates of organs recovered and transplanted vary according to organ (Table 1).
Approximately 17% to 20% of potential donors had a medical contraindication. Despite the presumed consent principle, approximately 30% to 33% of eligible brain death donors have either expressed a refusal for donation or had a refusal communicated by the next-of-kin, representing a major obstacle on the way to increase donation rates. In an attempt to increase the rate of potential donors while reducing refusal rates, the “Agence de la Biomédecine” has developed an effective system for an early identification and follow-up of all patients that may eventually be diagnosed as brain dead. The so-called Cristal Action Program includes a number of initiatives to raise awareness among healthcare professionals to educate them in communicating to the next of kin and to evaluate professional practices linked to the identification of potential donors. In more detail, this approach aims to reduce the current variability in donor management by implementing protocols of care that are validated by both intensive care Societies and the “Agence de la Biomédecine” to improve the coordination and communication. Of note, the “Agence de la Biomedecine” provides financial support to procurement centers based on their activity and develops guidelines educating and training Organ Procurement Organization teams.
DONATION AFTER CARDIAC DEATH
Procurement from donors after circulatory death (DCD) is supported in France since 2005, however, only for a limited number of pilot centers with a single national medical protocol issued by the “Agence de la biomédecine.”9 Initially, DCD donation had been limited to uncontrolled DCDs (uDCD, Maastricht I-II criteria). Since 2007, 432 renal transplants from uDCDs have been performed with an additional 19 DCD liver transplants since 2010. One-year graft survival for uDCD kidneys had been 87.2 % and 90.4% (death-censored), respectively. The procurement of deceased donors from controlled donors (Maastricht III) has been authorized in 2014 combined with guidelines for donor/recipient age, and ischemic times to improve graft survival while increasing the acceptance of DCD organs.10 During the last 18 months, a total of 35 procurements have been performed in 5 centers with 13 liver, 62 kidney, and 1 lung transplantations, all preserved under in situ normothermic conditions with excellent transplant outcomes. Of note, only 3.7% of in situ normothermically preserved kidney transplants had a DGF, whereas all liver grafts functioned immediately (manuscript in preparation).
GRAFTS OF SUBOPTIMAL QUALITY
The significant increase of the donor pool, which has been observed for 15 years, has mainly been linked to a more frequent utilization of expanded criteria donors (ECD), now referred to by United Network for Organ Sharing as donors with a kidney donor profile index > 85% (Figure 4). Although the number of young donors has been stable during the last years, even in the presence of declining death rates, an overall expansion has mainly been linked to the utilization of older donors or those with relevant comorbidities. Indeed, among brain dead donors, ECD donors have increased from 46% in 2009 to 54% in 2015. To optimally use those kidneys, cold ischemic times are kept short, pulsatile perfusion devices are being used (with a specific financial support from the Health ministry), donor and recipient age are being matched, and dual kidney transplants are being performed.11 For lung transplants, ECD donors (>55 years), with an oxygenation index (Pa)2/FIO2, P/F less than 300 mm Hg and chest x-ray abnormalities have been considered more frequently. At the same time, donor management has improved, all contributing to an overall increase of lung transplants by 58% during the recent 10 years (from 205 lung transplants in 2005 to 353 in 2015).
Outcomes of grafts procured from brain dead donors continue to be excellent with 1- and 5-year patient survival rates of 96.8% and 88.9% for kidney transplants, 84.7% and 72.5% in liver transplantation, 77% and 67,8% in cardiac transplantation, and 77.1% and 55.6% in lung transplantation.
Rates of living kidney donations have increased during the recent years. Legislative changes in 2005 allowed spouses and I-III degree relatives to donate while live donor registries have been established. Since 2011, individuals that have a “close and stable” relationship with the recipient for at least 2 years are allowed to donate and paired-kidney donation is permitted. Accompanied with a promotion of the living kidney donation program, these new regulatory rules and the development of ABO-incompatible transplants (12% of all living kidney transplant in 2015) have resulted into a very significant increase of living donation rates. Overall, living donors have increased by 93% during the recent 5 years now comprising 16% of all kidney transplantations.
Live donor liver transplants had an initial peak in 2008 (52 liver living transplants, representing 6.5% of all liver transplants). However, reports on morbidities and mortalities have contributed to skepticisms and, at this time, only 10 to 12 liver living transplants are performed per year with mainly left lateral lobes for pediatric recipients while almost exclusively using left hemihepatectomies for adult recipients.
Before live donation, any donor has to be approved by a living donor committee confirming an absence of coercion, attesting medical and psychosocial suitability, assuring that the donor is thoroughly informed of risks and benefits involved while understanding the implications of alternative treatments. Moreover, the relationship between donor and recipient requires confirmation by a judge.
France has contributed with pioneering work in organ transplantation. At this time, France performs the highest number of organ transplants per year in Europe.
During recent years, deceased donor rates have increased with the utilization of both controlled and uncontrolled DCD organs in addition to ECDs.
New legislation has allowed a tremendous increase of living donor kidney transplants. Although 16% of renal transplants are currently from living donors, there is room for further improvement.
The authors acknowledge the support by C. Legeai, MD, E. Savoye, C. Jasseron, L. Durand, and C. Cantrelle from the Statistics Department, Agence de la biomédecine.
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