Expanding the donor pool to increase renal transplantation.

INTRODUCTION: The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. METHODS: Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. RESULTS: Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P = 0.4). CONCLUSION: Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.     

尸体供者小肠、肝和肾脏器联合切取及保存技术

目的建立尸体供者全腹腔脏器切取和保存技术,同时为不同的小肠移植、肝移植和肾移植受者提供供器官。方法共进行8次同一尸体供者的全腹腔脏器切取手术。供体切取经腹主动脉与肠系膜下静脉插管,高渗枸橼酸-腺苷肾保存液及UniversityofWisconsin液原位灌注,肝、小肠、胰腺、脾、肾整块切取。供器官经后台修整后,分别成为肝、小肠和肾移植物进行相应的受者移植手术。结果 8次供者腹腔脏器切取和后台修整手术共获取8具小肠移植物、8具肝移植物和16具肾移植物。利用所修整出的供器官成功地完成5次单独小肠移植、8次肝移植和16次肾移植,术后移植物功能良好。结论所建立的尸体供者全腹腔脏器切取和保存技术,可同时为不同的小肠移植、肝移植和肾移植受者提供供器官;借鉴美国匹兹堡大学的供者器官后台分离技术,还可同时为胰腺移植受者提供供器官。     

Maximizing liver transplantation from non-heart-beating donors

In order to increase the supply of transplantable organs, an increasing number of organ procurement organizations are adopting policies regarding donations from non-heart-beating donors. Few centers, however, actually recover and transplant these organs. This article reviews a case in which kidneys and livers imported from out of state were successfully recovered from a non-heart-beating donor and transplanted. In addition, the article demonstrates how cooperation and flexibility in transplant personnel can increase the number of organs transplanted from a non-heart-beating donor.     

Optimizing outcomes by preconditioning the donor

The criteria that define a so-called “marginal donor” kidney have been standardized since 2002. However, every transplant center must establish its own guidelines on organ acceptability. An expanded criteria donor (ECD) kidney is age at least 60 years, or 50 to 59 years with at least two of three specified comorbidities. Cadaveric kidneys have shown worse functional and survival outcomes compared with those from living donors. Thus, all efforts should be made to minimize the effects of ischemia on standard, non-heart-beating or ECD cadaveric donor kidneys. Because of an increasing shortfall between the diminishing number of deceased donor organs available and the increasing waiting lists, an increasing number of living donor transplantations are being performed in Europe. Among deceased donor kidneys, the largest percentage corresponds to ECD—aged or comorbidity donors—and donors after cardiac death. The results of transplants with kidneys from donors over 65 years are 10% to 15% lower than those from younger donors. Older donors present more comorbidities; however, acceptable results may be obtained with careful selection and shortened cold ischemic times. If the transplant center uses these donors to expand the pool of available organs, the donor must be evaluated according to age, vascular condition, renal function, and comorbidity. If the donor is accepted, suitable questions are: Has the potential donor undergone maneuvers to improve the quality of the kidneys? Which kind of approaches should we perform? Should we only use the biopsy information for a decision?     

大白鼠无心跳供体肺移植的实验研究

目的　探讨不同热缺血时间对无心跳供体肺的组织结构和功能的影响及无心跳供体肺应用于肺移植的可能性。　方法　取 6 0只健康大白鼠 ,随机分成有心跳组、无心跳 缺血 30min组、无心跳 缺血 6 0min组 ,每组 10对 ,分别为供体和受体。有心跳组供体在处死的同时灌注 4℃低钾右旋糖苷液 ,无心跳 缺血 30min组、无心跳 缺血 6 0min组供体处死后维持辅助呼吸 ,分别放置室温中30和 6 0min ,再灌注低钾右旋糖苷液 ,供肺置于 4℃低钾右旋糖苷液中 4h。受体鼠行左侧开胸术和原位左肺移植术。术后维持辅助呼吸 1h ,经右侧进胸 ,阻断右肺门。　结果　无心跳 缺血 30min组存活时间均超过 30min ,肺顺应性为 0 .16 4 0± 0 0 0 4 9,动脉血氧分压 (85± 4 )mmHg ,动脉血二氧化碳分压 (41 9± 1 9)mmHg ,腺苷核苷酸总量 (75 8± 30 )mol/ g蛋白 ,超微结构改变为轻度的淤血和肺实质水肿 ,与有心跳组相比 ,差异均无显著意义 (P >0 0 5 )。无心跳 缺血 6 0min组有 4只 10min后心跳停止 ,3只 2 0min后心跳停止 ,与另两组相比 ,所测各项指标的差异有显著意义 (P <0 0 5 )。　结论　采用无心跳供体是增加供肺来源的一种安全而有效的方法 ,热缺血 30min大白鼠无心跳供体肺适于肺移植。     

Death and the potential organ donor

There is no statutory definition of death in the UK, but death is accepted as the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. Brainstem death is considered equivalent to somatic death. Brainstem death testing is a formalized process divided into three stages: preconditions, exclusions and clinical testing. The confirmation of brainstem death allows for heart-beating organ donation to proceed. The increasing demand for transplantable organs has not been matched by available heart-beating organ donors, leading to renewed interest in non-heart-beating donation. Improved preservation techniques and better assessment of organ function have enabled transplant teams to procure kidneys, livers, lungs and other tissues from non-heart-beating donors. Results from transplanted kidneys show identical five-year survival for organs taken from heart-beating and non-heart-beating donors.     

Non-heart-beating donor, renewal of an old procedure: a Belgian experience

The shortage of donated organs has become a problem in transplantation throughout the world. Transplant teams are looking for other ways to increase and improve the donor pool. Non-heart-beating donation may be a source to increase the number of donors, even if some technical, logistical, and emotional problems are encountered. The results obtained by our team should stimulate other centers to implement this kind of donation in their hospitals. We describe our experience in the policy of non-heart-beating donation and encourage transplant centers to develop such a program.     

Cadaveric renal transplantation from a non-heart-beating pediatric donor into adult recipients

INTRODUCTION: The use of cadaveric pediatric kidneys has been suggested as a means to overcome organ shortage, but is debated because of technical complications and an increased incidence of functional allograft impairment. METHODS: We experienced 2 cases of cadaveric renal transplantation from a non-heart-beating pediatric donor. RESULTS: In our cases, transplanted kidneys achieved good graft function and proteinuria due to glomerulosclerosis was not recognized. CONCLUSION: Previous reports indicate that in transplantation from pediatric donors into adults recipients, glomerular sclerosis occurs as the reason for impairment of grafts. Further, cadaveric renal transplantation from a non-heart-beating donor has a warm ischemia time and an increased risk of hyperfiltrated injury and graft failure. If transplantation of pediatric kidneys into adults from a non-heart-beating donor is performed, BMI and BSA must be carefully considered in the selection of recipients in order to avoid imbalance between nephron supply and metabolic demands and to insure successful, healthy grafts.     

Renal transplantation using non-heart-beating donors: a potential solution to the organ donor shortage in Canada.

INTRODUCTION: There is a chronic shortage of cadaveric organ donors for renal transplantation, which might be solved by the use of non-heart-beating donors (patients who suffer cardiac arrest and whose kidneys are harvested subsequently when irreversible heart and respiratory function occur). We carried out a chart review to determine whether the renal transplantation rate would improve if a non-heart-beating donor program was introduced at a Canadian centre. METHODS: We reviewed the charts of all 1547 patients who died in the emergency department or intensive care unit of the Ottawa Hospital, a tertiary care centre serving 1.2 million people in eastern Ontario, between January 1999 and May 2001. The number of potential non-heart-beating donors was determined by the use of predefined criteria. The number of additional kidneys that could be obtained with a non-heart-beating donor program was estimated and compared to the actual number of kidneys procured from conventional brain-dead donors during the same period. The potential increase in the renal transplantation rate was calculated. RESULTS: There were 83 potential non-heart-beating donors during the 29-month study period. The mean (and standard deviation) age of the donors was 40.6 (13.1) years, and 20% were female. The mean serum creatinine value was 75 (29) micromol/L; 44.6% of donors died secondary to trauma. We estimated that the use of non-heart-beating donors would have provided 14 to 41 additional donors during the study period (12-34 kidneys/yr). The cadaveric renal transplantation rate would have increased between 30% and 87%. CONCLUSION: The cadaveric renal transplantation rate could improve significantly if non-heart-beating donors were used in Canadian hospitals.     

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.     

Non-heart-beating donors: an excellent choice to increase the donor pool

A specific program was adopted to obtain organs, for transplant purposes from people who die at home or in the street from sudden or unexpected death (type I non-heart-beating donors [NHBD] according to the Maastricht classification). The objective of our program was to increase the donor pool by obtaining organs from well-selected potential donors who die at home, work, or in the street and are maintained on advanced life support (ALS) until hospital arrival. The great number of people who die in a previously healthy situation constitute an excellent source of organs for transplant purposes. Our program includes pre- and in-hospital attendance. Prehospital attendance is based on application of cardiopulmonary resuscitation in situ and ALS until arrival at hospital. In hospital, specific preservation maneuvers must be performed and family assessment and judge permission obtained. In the last 15 years, we developed a kidney transplant program with better results than transplants performed with organs obtained from encephalic death donors (EDD). A specific NHBD subprogram for lung transplant was developed with excellent results as well. We are now improving the liver transplant program. NHBD are an important source of human tissues, including pancreas islets. It is clear that NHBD are a great source of organs and tissues for transplant, and that this kind of program must be established in all countries in which legal regulations allow it.     

Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.     

Overview of the Belgian donor and transplant statistics 2006: results of consecutive yearly data follow-up by the Belgian Section of Transplant Coordinators

BACKGROUND: The Belgian Section of Transplant Coordinators, created in 1997 under the auspices of the Belgian Transplant Society, is in charge of the collection of the national data about donor/procurement activities. METHODS: Data are collected in all Belgian transplant centers. An annual report is finalized by combining these data with data from the Eurotransplant database. RESULTS: An increase of both potential donors (n = 501, +14.4%) and effective donors (n = 273, +16.7%) was observed in 2006 versus 2005. Among effective donors, 28 were non-heart-beating donors (10.25%). Overall donor ratio was 26.26 donors per million inhabitants. Within potential donors, absence of organ harvesting was due to medical contraindications (28%), family refusal (13%), or legal refusal (2%). Donor mean age was 46.4 years and mean organs/donor was 3.21 +/- 1.7. An overall reduction of Belgian waiting lists was observed in 2006 as compared with 2005 (-5.7% for kidney, -25.7% for liver, -9.4% for heart, -6.7% for lung, and -11.7% for pancreas), while waiting list mortality was 18% for liver, 11% for heart, and 7% for lung. As compared with 2005, transplant activities increased for kidney (n = 485, +24.3%), heart +/- lungs (n = 73, +7.3%), and lungs (n = 83, +39.4%) but decreased for liver (n = 236, -2.1%). Living donation represented 8.45% for kidney (+28.1% vs 2005) and 8% for liver transplantation (-29.6%). CONCLUSION: Globally, a marked increase of procurement and transplant activities was observed in 2006, allowing to limit waiting list and waiting list mortality. Further increase of living donor activity and non-heart-beating donation remains necessary to extend the donor pool.     

Myocardial viability twenty-four hours after orthotopic heart transplantation from non-heart-beating donors

OBJECTIVES: Using a new preservation strategy, we investigated the performance of hearts from non-heart-beating donors during an observation period of 24 hours after orthotopic heart transplantation in a pig model. METHODS: In the control group (n = 6) beating donor hearts were harvested with Bretschneider's HTK solution and transplanted orthotopically without reperfusion modifications. In the non-heart-beating donor group (n = 6) hearts were perfused with leukocyte-depleted blood cardioplegia after 30 minutes of normothermic ischemia. Blood cardioplegia was supplemented with a sodium-hydrogen exchange inhibitor and adenosine. After transplantation, a second controlled reperfusion with blood cardioplegia was performed. RESULTS: Preload recruitable stroke work of the left ventricle 24 hours after transplantation in the control versus non-heart-beating donor group was 108% +/- 24% versus 103% +/- 18% of baseline values. Myocardial blood flow of the left and right ventricle was increased to 146% +/- 32% and 176% +/- 51% in the control group versus 176% +/- 29% and 194% +/- 27% in the non-heart-beating donor group. Myocardial oxygen consumption was 11.2 +/- 2.1 versus 12.8 +/- 2.2 mL/100 g per minute at baseline and 11.6 +/- 2.6 versus 13.2 +/- 3.1 mL/100 g per minute after 24 hours (not significant). Histologic examination with Luxol fast blue staining revealed that 2.6% +/- 4.8% of myocytes in the control group versus 1.8% +/- 1.9% in the non-heart-beating donor group were damaged irreversibly. CONCLUSIONS: Recovery of donor hearts from non-heart-beating donors is comparable with recovery of organs harvested from heart-beating donors if the above-mentioned preservation technique is used. These results could encourage the use of marginal donor hearts and help to expand the limited donor pool.     

Effect of machine perfusion preservation on delayed graft function in non-heart-beating donor kidneys – early results

The functioning of non-heart-beating (NHB) donor kidneys upon transplantation is often delayed. To evaluate the effect of preservation by machine perfusion (MP) on early post-transplant function, 37 NHB donor kidneys were compared to 74 matched heart-beating (HB) donor kidneys preserved by cold storage (CS). The NHB donor kidneys were subject to 49 ± 34 min of warm ischemia. Delayed function (DF) and primary nonfunction (PNF) rates were significantly higher for NHB than for HB donor kidneys (49 % and 19 % vs 34 % and 7 %, respectively). Consequently, renal function was impaired but recovered within 6 months. MP could not eliminate the differences in DF rate between NHB and HB donor kidneys. However, NHB donor kidneys preserved by MP showed less DF than that reported in kidneys preserved by CS. This suggests that MP has a beneficial effect on ischemically damaged kidneys. The similar results observed with category 2 and category 3 NHB donors also suggest this effect. The high PNF rate emphasizes the need for viability tests that prevent the transplantation of nonviable organs. We conclude that MP alone is not sufficient to reduce DF and PNF rates in NHB donor kidneys. Received: 16 January 1997 Received after revision: 7 April 1997 Accepted: 11 April 1997     

Non-heart-beating donors from the streets: an increasing donor pool source

BACKGROUND: Non-heart-beating donors have become a source for organ donation, especially kidneys. The emergency room and the critical care unit are the two sources for this kind of donor. Three years ago, our hospital began a policy of obtaining organs and tissues successfully from subjects who died in the streets. METHODS: We consider as potential organ donors people who die out-of-hospital, are less than 50 years old, with less than 15 min of asystolia without cardiac massage, with a known etiology of death, and without general contraindications for donating. After death diagnosis, the cadaver is taken to the hospital where an emergency room doctor certifies the death. Afterward, the cadaver is transferred to the operating room where a cardiopulmonary bypass is performed to preserve the organs while the legal aspects of donation go on. RESULTS: Up to now, 111 cadavers have been taken as non-heart-beating donors; 53 of them have been actual donors. The average time before arrival to the hospital was 68+/-2.64 min, and the average interval between cardiac arrest and the beginning of cardiopulmonary bypass was 111.33+/-7.09 min. We have obtained 105 kidneys, 12 livers, 84 corneas, and 31 pancreata for islets isolation as well as 49 long bones. Seventy-two kidneys were transplanted, with a probability of survival of 83% at 36 months. CONCLUSIONS: Our experience indicates that it is possible to obtain organs for transplant from donors who die in the streets and are brought to the hospital under strict selection criteria.     

Development of a successful non-heart-beating organ donation program

To help alleviate the organ shortage, transplant centers are using organs from expanded-criteria donors, who were considered unsuitable just a few years ago, such as non-heart-beating donors. In 1998, we made a concerted effort to increase the number of non-heart-beating donors recovered by our organ procurement organization. In this paper, we discuss the steps in establishing this program, including transplant center support, estimating the number of potential non-heart-beating donors, organ procurement support, protocol development, hospital development, education, putting the protocol into practice, follow-up, and effect of the program on organ procurement. With the establishment of this program, the number of non-heart-beating donors increased from 2% to 5% per year to over 10% for the past 2 years. From these donors, 61 of 82 recovered kidneys were transplanted into 58 patients, and 18 of 20 recovered livers were transplanted. A non-heart-beating donor program can significantly add to the number of organ transplants and successful transplantations.     

Donation after cardiac death has a minimal impact on thoracic organ recovery

BACKGROUND: Our organ procurement organization recently developed an aggressive donation after cardiac death program. Thoracic organs are rarely recovered from non-heart-beating donors. Therefore, there is concern that donation after cardiac death may affect the recovery of thoracic organs from donors not allowed to progress to brain death. OBJECTIVE: To evaluate the potential impact of donation after cardiac death on the recovery of thoracic organs. METHODS: On the assumption that prolongation of care on all cases would result in a diagnosis of brain death. By retrospective chart review, all donations after cardiac death were evaluated for thoracic organ potential using the same standards that were used to evaluate brain-dead donors. RESULTS: During the study period there were 34 of 44 (77%) non-heart-beating donors qualified to donate abdominal organs only. Ten of 44 non-heart-beating donors (24%) qualified to potentially donate thoracic organs; the families of 4 of 10 of these donors insisted on the immediate withdrawal of life support, leaving only 6 donors with thoracic organ potential. All 6 of these donors qualified as potential heart donors and 3 as potential lung donors. CONCLUSIONS: A total of 97 organs were recovered and successfully transplanted from 44 non-heart-beating donors. If all the donors who qualified to donate thoracic organs progressed to brain death and if their thoracic organs were transplantable, then 6 additional hearts and 3 pairs of lungs may have been recovered. These data demonstrate that an aggressive donation after cardiac death program contributes significantly to the organ donor pool, with a minimal impact on potential thoracic organ recovery.     

Short-term inhaled nitric oxide in canine lung transplantation from non-heart-beating donor

BACKGROUND: Use of lungs harvested from non-heart-beating donors (NHBDs) would increase the pulmonary donor pool; however, this strategy would have higher risk of early postoperative graft dysfunction due to unavoidable warm ischemic time. We evaluated the effects of short-term inhaled nitric oxide (NO) during reperfusion in canine left single-lung allotransplantation from a non-heart-beating donor. METHODS: The donor dogs were sacrificed without heparinization and left at room temperature for 3 hours. Then, recipient dogs received a left single-lung allotransplantation. After implantation, the right bronchus and pulmonary artery were ligated. In group 1 (n = 6), NO gas was administered continuously at a concentration of 40 parts per million throughout a 6-hour assessment period. In group 2 (n = 6), NO gas was administered for the initial 1 hour during reperfusion. In group 3 (n = 6), nitrogen gas was administered for control. RESULTS: Groups treated with NO exhibited lower pulmonary vascular resistance, as well as improved survival and oxygenation. There was no significant difference in these parameters between group 1 and group 2. Myeloperoxidase activity was significantly lower in NO-treated groups. CONCLUSIONS: Inhaled NO during reperfusion is beneficial in lung transplantation from non-heart beating donors. The beneficial effect is obtained mainly during the first hour of reperfusion.     

Recommendations for the use of extended criteria donors in lung transplantation

Selection criteria for lung donation were based on initial experiences with lung transplantation without further studies to improve them, thereby guaranting the best use of donated organs. A definition of an extended criteria donor is therefore required to obtain more lungs to meet the demands of patients awaiting transplantation. Studies have been reviewed for the impact on survival and morbidity of age ranges, oxygen fraction, cause of death, smoking habits, x-ray findings, infection, hepatitis serology and non-heart-beating status, seeking to support physicians to make decisions regarding the use of marginal organs.