Cadaveric donor selection and management

While there is little doubt that proper donor selection is extremely important to achieve good outcomes from transplantation, there are only limited data regarding the current criteria utilized to select the "ideal donor". Importantly, there are not enough donor lungs available for all of those in need. Until an adequate supply of donor organs exists, lives will be lost on the transplant waiting list. While efforts have been made to increase donor awareness, additional transplants can be realized by improving donor utilization. This can be achieved by active participation of transplant teams in donor management and by utilizing "extended criteria" organs. Further studies are needed to assess the impact of using "extended criteria" donors, as this practice could result in increased posttransplant morbidity and mortality. This article summarizes the approach to identification of potential lung donors, optimal donor management, and the clinical importance of various donor factors upon recipient outcomes.     

Maximizing the donor pool: marginal donors, splits, and living donor liver transplants

Abstract   The shortage of donor organs is probably the biggest problem facing the field of liver transplantation today. Waiting lists have grown dramatically in the last 10 years. The consequences of this have been multiple, including higher waiting list mortality rates, longer waiting times, and more advanced liver disease in those patients coming to transplant. To address this issue, transplant centers are utilizing several techniques in an effort to expand the donor pool. These include the use of marginal donors (donors that would not have been considered suitable for donation previously), the use of living donors, and performing split liver transplants from deceased donors. The obvious advantage of these procedures is to expand the donor pool, hence increasing the number of transplants, and thus hopefully decreasing waiting list mortality rates. The disadvantage is that in many instances, such transplants may yield inferior results compared to standard transplants, or be associated with a higher incidence of complications. Further experience with such types of transplants will hopefully help to improve results and define the ideal manner in which to use these techniques to maximize the number of transplants.     

The challenge of improving donor heart preservation

Heart transplantation has in recent years become the treatment of choice for end stage heart failure. However while the waiting list for transplantation is growing steadily, the donor pool is not increasing. Therefore, in order to meet demand, transplant programs are using older, "marginal donors" and accepting longer ischaemic times for their donor hearts. As donor organs are injured as a consequence of brain death, during the period of donor management, at organ harvest, preservation, implantation and reperfusion, expansion of acceptance criteria places a great burden on achieving optimal long-term outcomes. However, at each step in the process of transplantation strategies can be employed to reduce the injury suffered by the donor organs. In this review, we set out what steps can be taken to improve the quality of donor organs.     

Living lobar lung transplantation

A constant awareness of the risk to the living donors must be maintained with any live-donor organ transplantation program, and comprehensive short- and long-term follow-up should be strongly encouraged to maintain the viability of these potentially life-saving programs. There has been no perioperative or long-term mortality following lobectomy for living lobar lung transplantation, and in the authors' series the perioperative risks associated with donor lobectomy are similar to those seen with standard lung resection. These risks might increase if the procedure were offered on an occasional basis and not within a well-established program. Further long-term outcome data, similar to data for live-donor renal and liver transplantation, are needed. Therefore, the authors still favor performing living lobar lung transplantation only for the patient with a clinically deteriorating condition. They believe that prospective donors should be informed of the morbidity associated with donor lobectomy and the potential for mortality, as well of potential recipient outcomes in regard to life expectancy and quality of life after transplantation. A major question regarding lobar lung transplantation that has been unanswered during the last decade has been defining when a potential recipient is too ill to justify placing two healthy donors at risk of donor lobectomy. Recipient age, gender, indication for primary transplant, prehospitalization status, preoperative steroid usage, relationship of donor to recipient, and the presence or absence of rejection episodes postoperatively do not seem to influence overall mortality. Patients receiving mechanical ventilation preoperatively and those undergoing retransplantation after either a previous cadaveric or lobar lung transplantation have significantly elevated odds ratios for postoperative death. The authors therefore recommend caution in these subgroups of patients. This experience is similar to the cadaveric experience in which intubated patients have higher I-year mortalities and patients undergoing retransplantation have decreased 3- and 5-year survival. A similar experience with a smaller number of lobar transplants has been reported by the Washington University group. Despite the high-risk patient population, this alternative procedure has been life saving in severely ill patients who would die or become unsuitable recipients before a cadaveric organ becomes available. Although cadaveric transplantation is preferable because of the risk to the donors, living lobar lung transplantation should continue to be used under properly selected circumstances. Although there have been no deaths in the donor cohort, a risk of death between 0.5% and 1% should be quoted pending further data. These encouraging results are important if this procedure is to be considered as an option at more pulmonary transplant centers in view of the institutional, regional, and intra- and international differences in the philosophical and ethical acceptance of the use of organs from live donors for transplantation.     

Matching donor to recipient in liver transplantation: Relevance in clinical practice

Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors’ clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.     

The Evolution of Living Kidney Donation and Transplantation in Older Adults

Kidney transplantation is a good option for adults aged 65 and older with end‐stage renal disease because it has been shown to reduce morbidity and mortality, improve quality of life, and is more cost‐effective than other renal replacement options. However, older age has been a deterrent to access to the deceased donor waiting list, and individuals aged 65 and older have a lower probability of being referred to and listed for transplantation compared to younger adults. Because the deceased organ supply is limited, living donor kidney transplantation offers an effective alternative for older adults facing long waiting times for cadaveric organs. This article describes the evolution of living kidney donation and transplantation in older adults over 15 years using the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database. Between 1997 and 2011, 28,034 kidney transplantations were performed in adults aged 65 and older. Living‐donor and cadaveric kidney transplantation increased in older adults over the 15‐year period. Offspring are the most common living donors in this age group, followed by unrelated donors (e.g., friends), whereas the most common donors in younger transplant recipients are spouses, siblings, and parents. The number of living kidney donors aged 65 and older is slowly increasing, although the total number of transplants in this age group remains low. The expansion of living‐donor kidney transplantation in the aging population may offer a solution for organ shortage and thereby improve the quality of life of older adults. More research is needed to understand the older donor–recipient relationship and barriers to transplantation in this population.     

Approaching the sensitized lung patient: risk assessment for donor acceptance

The presence of HLA antibodies is widely recognized as a barrier to solid organ transplantation, and for lung transplant candidates, it has a significant negative impact on both waiting time and waiting list mortality. Although HLA antibodies have been associated with a broad spectrum of allograft damage, precise characterization of these antibodies in allosensitized candidates may enhance their accessibility to transplant. The introduction of Luminex-based single antigen bead (SAB) assays has significantly improved antibody detection sensitivity and specificity, but SAB alone is not sufficient for risk-stratification. Functional characterization of donor-specific antibodies (DSA) is paramount to increase donor accessibility for allosensitized lung candidates. We describe here our approach to evaluate sensitized lung transplant candidates. By employing state-of-the-art technologies to assess histocompatibility and determine physiological properties of circulating HLA antibodies, we can provide our Clinical Team a better risk assessment for lung transplant candidates and facilitate a “road map” to transplant. The cases presented in this paper illustrate the “individualized steps” taken to determine calculated panel reactive antibodies (cPRA), titer and complement-fixing properties of each HLA antibody present in circulation. When a donor is considered, we can better predict the risk associated with potentially crossing HLA antibodies, thereby allowing the Clinical Team to approach allosensitized lung patients with an individualized medicine approach. To facilitate safe access of sensitized lung transplant candidates to potential donors, a synergy between the histocompatibility laboratory and the Clinical Team is essential. Ultimately, donor acceptance is a decision based on several parameters, leading to a risk-stratification unique for each patient.     

Lungentransplantation

Since the early days of lung transplantation the demand for donor organs has outstripped donor organ availability. Consequently waiting times continue to increase with patients of highest priority often waiting several weeks or even months until a suitable donor organ becomes available resulting in considerable mortality on the waiting list. These issues have led to renewed interest in bridging strategies for patients with end-stage lung disease. The use of endotracheal intubation and mechanical ventilation (MV) has been viewed as a last resort as the majority of intubated patients fail to reach transplantation and those who do tend to have a poor postoperative outcome. New bridging strategies with awake extracorporeal membrane oxygenation (ECMO) seem to be hopeful alternatives in some patients. In the early intensive care unit (ICU) phase primary graft dysfunction, acute rejection, infections and surgical complications are common problems. Later, rejection, infection and sepsis, special airway complications and pulmonary bleeding may be reasons for ICU treatment.     

Living donor liver transplantation.

Initially living donor liver transplantation (LDLT) was almost exclusively performed in infants and children. Adult LDLT programmes were initiated several years later. In the west this programme was introduced in view of a critical shortage of deceased donors and a constant increase in waiting list mortality. At present, this procedure is accepted as a therapeutic option for patients with end-stage liver disease to make up for the shortage of donor organs from dead patients. In Asia, however, LDLT has become the predominant means of liver transplantation as donor organs from the diseased cannot be used for religious and ethical reasons. Although there have been significant improvements in surgical techniques and consequently in recipient outcome over recent years, the LDLT procedure is still associated with donor morbidity and even mortality. The overall reported donor mortality was 0.2% and donor morbidity ranged between 0% and 100%. Biliary complications and infections were the most commonly reported donor complications. Therefore, a thorough medical as well as psychological evaluation of the donor and recipient are necessary prior to this procedure. To date, LDLT comprises less than 5% of adult liver transplantations in Europe and in the United States. Recipient and graft survival are almost identical to those seen with liver transplantations from deceased donors (DD). Biliary and vascular complications are more often seen in the LDLT setting. So far, no studies have focussed on the impact of LDLT on waiting list mortality. There is international consensus that this procedure should be restricted to centres with large experience in deceased donor liver transplantations as well as in hepatobiliary surgery. Ethical issues, optimal utility and application of adult LDLT and optimal recipient and donor characteristics have yet to be defined.     

Selection and management of the lung donor

This article reviews recent developments in the selection, assessment, and management of the potential lung donor that aim to increase donor organ use. The scarcity of suitable donor organs results in long waiting times and significant mortality for those patients awaiting transplant. Strategies to expand the donor pool can substantially improve donor lung use rates. Although further long-term studies are required to confirm that long-term outcomes are not being compromised, the available evidence suggests that the traditional factors defining a lung as marginal or extended do not actually compromise outcomes within the framework of current donor management strategies.     

Kidney transplantation from donors with hepatitis C infection

The increasing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led to most transplant centers developing protocols that allow safe utilization from donors with special clini cal situations which previously were regarded as contra indications.Deceased donors with previous hepatitis C infection may represent a safe resource to expand the donor pool.When allocated to serology-matched recipi ents,kidney transplantation from donors with hepatitis C may result in an excellent short-term outcome and a significant reduction of time on the waiting list.Specia care must be dedicated to the pre-transplant evaluation of potential candidates,particularly with regard to live functionality and evidence of liver histological damage such as cirrhosis,that could be a contraindication to transplantation.Pre-transplant antiviral therapy could be useful to reduce the viral load and to improve the long-term results,which may be affected by the progression of liver disease in the recipients.An accurate selection of both donor and recipient is mandatory to achieve a satisfactory long-term outcome.     

The use of marginal grafts in liver transplantation

Because of the shortage of organ supplies, more transplant programs have begun to use marginal grafts in liver transplantation. A number of single-center experiences with marginal grafts have yielded encouraging results, but recent analyses using nationwide databases show that outcomes are inferior to results with normal whole-liver grafts. Use of marginal grafts is still acceptable, however, and plays an important role in expanding the donor pool and decreasing mortality on the waiting list. In the broadest terms, national data and single-center experiences show that: (1) there is no limit in donor age for liver transplantation, (2) appropriate selection of steatotic livers improves outcomes, (3) prolonged graft ischemia is a preventable factor, (4) livers from donors with hepatitis B or C virus can be safely transplanted, and (5) adequate prophylaxis prevents recurrence of hepatitis B without significant graft loss. In addition, grafts procured after cardiac death are another growing source of marginal grafts. Transmission of malignancy from donors is rare but life-threatening. Reduced-size grafts from living-donor or split-liver transplantation have shown similar outcomes to whole-liver transplantation. In this review, we will discuss the current status of the utility of these marginal grafts in liver transplantation.     

Current challenges and future directions for liver transplantation

Liver transplantation is an effective and widely used therapy for several patients with acute and chronic liver diseases. The discrepancy between the number of patients on the waiting list and available donors remains the key issue and is responsible for the high rate of waiting list mortality. The recent news is that the majority of patients with hepatitis C virus related liver disease will be cured by new antivirals therefore we should expect soon a reduction in the need of liver transplantation for these recipients. This review aims to highlight, in two different sections, the main open issues of liver transplantation concerning the current and future strategies to the best use of limited number of organs. The first section cover the strategies to increase the donor pool, discussing the use of older donors, split grafts, living donation and donation after cardiac death and mechanical perfusion systems to improve the preservation of organs before liver transplantation. Challenges in immunosuppressive therapy and operational tolerance induction will be evaluated as potential tools to increase the survival in liver transplant recipients and to reducing the need of re‐transplantation. The second section is devoted to the evaluation of possible new indications to liver transplantation, where the availability of organs by implementing the strategies mentioned in the first section and the reduction in the number of waiting transplants for HCV disease is realized. Among these new potential indications for transplantation, the expansion of the Milan criteria for hepatocellular cancer is certainly the most open to question.     

Ethical tensions in solid organ transplantation： The price of success

Solid organ transplantation has rapidly developed into the therapy a choice for end-stage organ failure. The expansion of its use has resulted is a large deficiency in organ supply. To address this, the field of organ transplantation has attempted to develop new strategies that would increase the availability of organs for transplant. Some of these strategies include expansion of the donor pool by increasing the number of living donors or using deceased donor organs that may be marginal or "expanded". The intent is to bring life-saving therapy to individuals in need; however, much of this expansion has been brought forward without clear prospective guidelines. This article focuses on the current disparity between organ supply and demand, and how this has impacted the use of living donors and development of the "expanded donor" concept.     

Mechanical circulatory support in lung transplantation: Cardiopulmonary bypass,extracorporeal life support,and ex-vivo lung perfusion

Lung transplant is the standard of care for patients with end-stage lung disease refractory to medical management. There is currently a critical organ shortage for lung transplantation with only 17% of offered organs being transplanted. Of those patients receiving a lung transplant, up to 25% will develop primary graft dysfunction, which is associated with an 8-fold increase in 30-d mortality. There are numerous mechanical lung assistance modalities that may be employed to help combat these challenges. We will discuss the use of mechanical lung assistance during lung transplantation, as a bridge to transplant, as a treatment for primary graft dysfunction, and finally as a means to remodel and evaluate organs deemed unsuitable for transplant, thus increasing the donor pool, improving survival to transplant, and improving overall patient survival.     

Risk factors for liver transplantation waiting list mortality

BACKGROUND AND AIM: The gap between the demand for liver transplantation and organ donation rates has a major impact on waiting list mortality. Understanding the risk factors that predict liver transplant waiting list death may help optimize organ allocation policy and reduce waiting list deaths. METHODS: We analyzed risk factors associated with waiting list mortality in the Liver Transplant Unit Victoria for the period 1988 through 2004. RESULTS: The mean annual waiting list mortality for the period examined was 10.2% (10.6% for adult and 6.4% for pediatric patients). Factors associated with waiting list death included female sex, fulminant hepatic failure, primary non-function, blood group O, more urgent United Network for Organ Sharing (UNOS)-derived medical status, a Child-Turcotte-Pugh (CTP) score >or=11, a model for end-stage liver disease (MELD) score >or=20, and a pediatric end-stage liver disease score >or=20. UNOS-derived medical status, CTP class, and MELD score were significant at the multivariate level. CONCLUSIONS: Disease severity scores, such as MELD, predict the risk of liver transplantation waiting list mortality. Use of such scores in organ allocation in Australian liver transplant units may result in reduced waiting list mortality.     

Live donors in liver transplantation

Living donor liver transplantation (LDLT) has been controversial since its inception. Begun in response to deceased donor organ shortage and waiting list mortality, LDLT was initiated in 1989 in children, grew rapidly after its first general application in adults in the United States in 1998, and has declined since 2001. There are significant risks to the living donor, including the risk of death and substantial morbidity, and 2 highly publicized donor deaths are thought to have contributed to decreased enthusiasm for LDLT. Significant improvements in outcomes have been seen over recent years, and data, including from the National Institutes of Health-funded Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL), have established a survival benefit from pursuing LDLT. Despite this, LDLT still composes less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors compose approximately 40% of all transplantations performed. The ethics, optimal utility, and application of LDLT remain to be defined. In addition, most studies to date have focused on posttransplantation outcomes and have not included the effect of the learning curve on outcome or the potential impact of LDLT on waiting list mortality. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

Organ allocation in lung transplant

Since the first successful single-lung transplant in 1983 and double-lung transplant in 1986, thousands of patients have benefited from the procedures. Until 1995, allocation of donor lungs was based purely on time on the waiting list. In 1995, a 90-day credit was given to patients with idiopathic pulmonary fibrosis, while still maintaining allocation based on waiting list time. In 2005, the lung allocation score (LAS) was implemented, dramatically changing the way lungs are allocated. This article will explore the reasons for the creation of the LAS, the design of the score, early experience with transplant results under the new system, and further changes that may be made to the system of lung allocation. As surgical techniques and medical management evolve, so to will the management of potential donors and the allocation of their organs, with the aim of benefiting patients needing lung transplantation in the United States.     

Liver transplantation in adults: Choosing the appropriate timing

Liver transplantation is indicated in patients with acute liver failure,decompensated cirrhosis,hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs.Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution.Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history.However,because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other,patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical,surgical and psychological contraindications.Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity.Thus,the appropriate timing of transplantation depends on recipient disease severity and,although this is still a matter of debate,also on donor quality.These two variables are known to determine the "transplant benefit"(i.e.,when the expected patient survival is better with,than without,transplantation) and should guide donor allocation.     

Donor management in cardiac transplantation

The most important limitation in organ transplantation is donor availability. Canada is facing a serious situation with respect to organ donation rates and transplantation. The number of patients listed for heart transplant continues to increase while the number of available donors has plateaued. Several steps can be taken to address this growing mismatch. The proper identification and assessment of potential donors together with improvements in medical management may increase the donor pool. Additionally, the use of marginal donors and the development of new organ preservation techniques may lead to an increase in the number of potential heart transplants in Canada. This paper summarizes the identification, evaluation and management of heart transplant donors, and defines strategies to improve procurement activity in heart transplantation.