Cadaveric donor selection and management

The current availability of lung donors is far exceeded by the number of potential transplant recipients who are waiting for an organ. This disparity results in significant morbidity and mortality for those on the waiting list. Although it is desirable to increase overall consent rates for organ donation, doing so requires an intervention to affect societal response. In contrast, increased procurement of organs from marginal donors and improved donor management may be realized through increased study and practice changes within the transplant community. Transplantation of organs from marginal or extended-criteria donors may result in some increase in complications or mortality, but this possibility must be weighed against the morbidity and risk of death risk faced by individuals on the waiting list. The effects of this trade-off are currently being studied in kidney transplantation, and perhaps in the near future lung transplantation may benefit from a similar analysis. Until that time, the limited data regarding criteria for donor acceptability must be incorporated into practice to maximize the overall benefits of lung transplantation.     

Expanding the donor pool for liver transplantation

Because of the growing shortage of donor organs, physicians and organ procurement agencies are expanding the donor pool through three mechanisms. The first mechanism is to increase the number of patients (and their families) who give consent for organ donation and thus extend the number of cadaveric livers. The second mechanism is that marginal livers, previously considered unacceptable for transplantation, are now being successfully transplanted. The third way to expand the donor pool is through advances in medical practice such as living-donor liver transplantation and split-liver transplantation.     

The net transfer of transplant organs across race, sex, age, and income

PURPOSE: To determine how sociodemographic characteristics influence both access to transplantation and organ donation. METHODS: For all transplants in the United States from 1996 to 2001, donor-recipient pairs were categorized as white-white, white-black, black-white, or black-black. The difference in the percentage of white-black versus black-white pairs was calculated as a measure of the net transfer of organs from one racial group to another. A similar approach was used to examine the net transfer of organs across other sociodemographic categories. RESULTS: Among cadaveric renal transplants, 66% of donor-recipient pairs were white-white, 23% were white-black, 5% were black-white, and 6% were black-black. Thus, there was an 18% net transfer of organs from white donors to black recipients (23% minus 5%). Among living donor transplants involving spouses, there was a 36% net transfer from wives to husbands. Among all cadaveric transplants, there was a 36% to 68% net transfer from younger donors to older recipients. Among cadaveric nonrenal transplants, there was a 7% to 18% net transfer from lower-income donors to higher-income recipients. CONCLUSION: The sociodemographic characteristics of persons who donate organs and those who benefit from organ transplantation differ markedly. Efforts to improve access and increase donation should address these differences.     

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.     

Surgical advances in liver transplantation. Living related and split donors

Surgical innovations to expand an exceedingly small cadaveric liver pool have paved the way for the more complex procedure of adult-to-adult living donation. Although reduced-size liver transplant (RSLT) has provided children and small adults with much needed small size grafts, discarding a part of the liver can no longer be justified in the current era of severe organ shortage. Split liver transplantation may eliminate the need for RSLT and may replace adult-to-adult pediatric donation except in urgent situations. Adult-to-adult living donation is a formidable undertaking that tremendously impacts adult recipients. Adult-to-adult living donation should be approached cautiously to ensure the safety of living donors. Expansion of adult living donation can only be achieved when ethical issues of donation are resolved and long-term donor safety is established.     

The path not taken: social and cultural barriers to thoracic transplantation

Religious beliefs, misperceptions, and distrust of the health care system have been cited as barriers to organ donation or transplantation in minorities. Improved training of hospital staff on donation protocols has been demonstrated to increase consent rates for or-gan donation. Increased interaction of minorities with ethnically appropriate transplant candidates, recipients, and donation or procurement personnel has a positive effect on donor rates. Programs using such practices must be expanded to overcome significant barriers to the transplantation of solid organs. Research into additional ways to improve acceptance of organ transplantation by minorities is needed to increase participation rates.     

Effect of race upon organ donation and recipient survival in liver transplantation

The effect of the race of the donor on organ donation and on the outcome of clinical liver transplantation has not been addressed previously. The aims of this study were to determine: (1) the number of organs donated by each of the major racial groups of the United States, (2) the outcome of transplantation of these organs across racial groups, and (3) the pattern of liver disease that required transplantation in each of these racial groups. A significantly higher proportion of organs were donated by white non-Hispanic Americans than either black or Hispanic Americans. There was no significant difference in survival when an organ was transplanted between black and white Americans and vice versa. Postnecrotic cirrhosis from a variety of causes was the most common indicator affecting black and white recipients, while primary biliary cirrhosis and primary sclerosing cholangitis were uncommon in the black population. While the number of organs donated by blacks was low, it was, however, proportional to the number of black recipients in this study. Reasons for the low rate of donation by the black and white Hispanic population are discussed. It is concluded that race is not a criteria to be used in selection of donors for liver transplantation. Educational programs addressing issues of organ donation and transplantation directed towards the black and Hispanic populations are recommended.Supported by research grants from the Veterans Administration, Project Grant DK 29961 from the National Institutes of Health, Bethesda, Maryland, and from the NIDDK 32556.     

Responsibilities of primary physicians in organ donation

As transplantation success rates have improved, the demand for donor organs has steadily increased. A shortage of donor organs has led to legislation requiring hospital personnel to provide families routinely with the opportunity to authorize organ donation. Primary physicians have an important role in identifying potential donors while continuing to assure that the survivors' needs are met. The major implications of organ donation for the primary physician are reviewed. Patients who die will more frequently be eligible as cornea, skin, or bone donors, but the criteria for both tissue and internal organ donation are reviewed. Ethical issues unique to organ donation and responses of survivors to donation requests are described. If appropriately offered, the opportunity to authorize an anatomic gift can be a source of comfort to survivors while the donation provides the benefits of transplantation to persons on organ waiting lists.     

A review of split liver transplantation with full right/left hemi-liver grafts for 2 adult recipients

Liver transplantation has become a routine operation in many transplantation centers worldwide. However, liver graft availability fails to meet patient demands. Split liver transplantation (SPLT), which divides a deceased donor liver into 2 partial liver grafts, is a promising strategy for increasing graft availability for transplantation and ameliorating organ shortage to a certain degree. However, the transplantation community has not yet reached a consensus on SPLT because of the variable results. Specifically, SPLT for 2 adult recipients using full right/left hemi-liver grafts is clinically more challenging in terms of surgical technique and potential postoperative complications. Therefore, this review summarizes the current status of SPLT, focusing on the transplantation of adult recipients. Furthermore, the initiation of the SPLT program, donor allocation, surgical aspects, recipient outcomes, and obstacles to developing this procedure will be thoroughly discussed. This information might help provide an optimal strategy for implementing SPLT for 2 adult recipients among current transplantation societies. Meanwhile, potential obstacles to SPLT might be overcome in the near future with growing knowledge, experience, and refinement of surgical techniques. Ultimately, the widespread diffusion of SPLT may increase graft availability and mitigate organ donation shortages.     

Split liver transplantation: Current developments

In 1988, Rudolf Pichlmayr pioneered split liver transplantation(SLT), enabling the transplantation of one donor liver into two recipients-one pediatric and one adult patient. In the same year, Henri Bismuth and colleagues performed the first full right/full left split procedure with two adult recipients. Both splitting techniques were rapidly adopted within the transplant community. However, a SLT is technically demanding, may cause increased perioperative complications, and may potentially transform an excellent deceased donor organ into two marginal quality grafts. Thus, crucial evaluation of donor organs suitable for splitting and careful screening of potential SLT recipients is warranted. Furthermore, the logistic background of the splitting procedure as well as the organ allocation policy must be adapted to further increase the number and the safety of SLT. Under defined circumstances, in selected patients and at experienced transplant centers, SLT outcomes can be similar to those obtained in full organ LT. Thus, SLT is an important tool to reduce the donor organ shortage and waitlist mortality, especially for pediatric patients and small adults. The present review gives an overview of technical aspects, current developments, and clinical outcomes of SLT.     

Debate on live related liver transplant: Pro

Abstract   Live donor liver transplantation (LDLT) in adults is life saving for patients with fulminant hepatic failure, acute on chronic liver failure and end-stage cirrhosis, particularly in Asia where cadaveric organ donation is scarce. Without this modality, 50% of adult patients waiting for deceased donor liver grafts and 95% of patients with fulminant hepatic failure died. With right lobe LDLT, the overall survival rate of patients with fulminant hepatic failure increases from 5–50% and the transplant rate of patients waiting for deceased donor grafts increased from 13–42%.     

How to evaluate organ donation: the quality programme in Tuscany

The shortage of cadaveric organ donors imposes a severe limit on the number of patients who can benefit from transplantation. This paper describes a programme for evaluation and improvement of the organ donation process, which has been implemented in the hospitals of the Tuscany region, Italy. After analysing the first results it was found that there was great potential for growth, especially in those hospitals with neurosurgery where the weakest points of the process were detected The development of a quality improvement programme in cadaveric organ donation is an adequate and scientific method to detect where the problems in the process of organ donation lie. Ideally, the comparison of these data with those of other Italian or European regions should be very useful to plan adequate strategies to improve cadaveric organ donation.     

Donation after cardio-circulatory death liver transplantation

The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.     

The clinical consequences of utilizing donation after cardiac death liver grafts into hepatitis C recipients

Abstract  

Chronic liver failure from hepatitis C virus (HCV) remains the leading indication for liver transplantation (LT). Donation after cardiac death (DCD) donors are becoming a more frequent source of liver grafts. Hepatitis C recipients of standard donation after brain death (DBD) allografts may have inferior long-term results, and more so when expanded criteria organs are used. Given the nature of DCD grafts, a focus on the consequences to HCV recipients is of major importance. We analyzed the graft outcomes in HCV and non-HCV liver transplant recipients of DCD grafts.     

Liver grafts from hepatitis B surface antigen-positive donors: A review of the literature

The scarcity of available organs and the gap between supply and demand continue to be the main limitations of liver transplantation. To relieve the organ shortage, current transplant strategies have implemented extended criteria, which include the use of liver from patients with signs of past or present hepatitis B virus (HBV) infection. While the use of liver grafts from donors with evidence of past HBV infection is quite limited, some data have been collected regarding the feasibility of transplanting a liver graft from a hepatitis B surface antigen (HBsAg) positive donor. The aim of the present work was to review the literature regarding liver transplants from HBsAg-positive donors. A total of 17 studies were identified by a search in Medline. To date, HBsAg positive grafts have preferentially been allocated to HBsAg positive recipients. The large majority of these patients continue to be HBsAg positive despite the use of immunoglobulin, and infection prevention can only be guaranteed by using antiviral prophylaxis. Although serological persistence is evident, no significant HBV-related disease has been observed, except in patients coinfected with delta virus. Consistently less data are available for HBsAg negative recipients, although they are mostly promising. HBsAg-positive grafts could be an additional organ source for liver transplantation, provided that the risk of reinfection/reactivation is properly prevented.     

Personnel in cadaveric organ transplant-related hospital units faced with living liver donation: an attitudinal study in a Spanish hospital with a cadaveric and living liver transplant programme.

INTRODUCTION: The attitude of health-care personnel is fundamental for the procurement of transplant organs, especially in those services that are related to transplantation. The objective of this study is to find out the attitude towards living liver donation among personnel who work in transplant-related services in a hospital with a cadaveric and living organ transplant programme. MATERIALS AND METHODS: A random sample was taken and stratified by type of service and job category (N=330), in services related to transplantation (procurement units, transplant units and follow-up units). Attitude was evaluated using a validated psychosocial questionnaire. Control group: a random sample of personnel in clinical services that do not have any direct contact with solid organ transplantation. Student's t-test and the chi(2) test complemented by a logistical regression analysis were applied in the statistical analysis. RESULTS: The questionnaire completion rate was 94% (N=309). Only 10% (N=31) of respondents are in favour of living liver donation if it is unrelated, but another 67% (N=207) are in favour if donation were for a relative. Of the rest, 11% (N=33) do not agree with living liver donation and the remaining 12% (N=38) are undecided. In the control group, attitude towards living liver donation is favourable in 82% (N=344) (P=0.0908). An analysis of the variables that influence attitude shows that the following factors are significantly related: (1) age (P=0.037); (2) a respondent's belief that he or she may need a transplant in the future (P=0.013); and (3) if it were necessary, a willingness to receive a donated living liver organ (P=0.000). Of the variables that have the most influence on attitude towards living liver donation in the bivariate analysis, there are two variables that are statistically significant in the multivariate analysis: (1) age and (2) willingness to accept a donated living liver organ from a relative if it were needed (OR=14.19). There is also a close relationship between attitude towards living liver donation and attitude towards living kidney donation (P=0.000) CONCLUSIONS: There is a favourable attitude towards living liver donation among personnel in units related to the transplantation and donation process, although it is less favourable than expected. Therefore, it will be necessary to increase this level of acceptance and to improve information about the matter if we want to encourage living liver donation. The youngest workers in these units are those who are most in favour, which leads us to believe that there is a hopeful future for this type of liver donation that is so necessary given the cadaveric organ deficit.     

The deceased organ donor with an “open abdomen”: proceed with caution

In solid organ transplantation, the disparity between donor supply and patients awaiting transplant continues to increase. The organ shortage has led to relaxation of historic contraindications to organ donation. A large percentage of deceased organ donors have been subjected to traumatic injuries, which can often result in intervention that leads to abdominal packing and intensive care unit resuscitation. The donor with this “open abdomen” (OA) presents a situation in which the risk of organ utilization is difficult to quantify. There exists a concern for the potential of a higher risk for both bacterial and fungal infections, including multidrug‐resistant (MDR) pathogens because of the prevalence of antibiotic use and critical illness in this population. No recommendations have been established for utilization of organs from these OA donors, because data are limited. Herein, we report a case of a 21‐year‐old donor who had sustained a gunshot wound to his abdomen, resulting in a damage‐control laparotomy and abdominal packing. The donor subsequently suffered brain death, and the family consented to organ donation. A multiorgan procurement was performed with respective transplantation of the procured organs (heart, liver, and both kidneys) into 4 separate recipients. Peritoneal swab cultures performed at the time of organ recovery grew out MDR Pseudomonas aeruginosa on the day after procurement, subsequently followed by positive blood and sputum cultures as well. All 4 transplant recipients subsequently developed infections with MDR P. aeruginosa, which appeared to be donor‐derived with similar resistance patterns. Appropriate antibiotic coverage was initiated in all of the patients. Although 2 of the recipients died, mortality did not appear to be clearly associated with the donor‐derived infections. This case illustrates the potential infectious risk associated with organs from donors with an OA, and suggests that aggressive surveillance for occult infections should be pursued.     

Ethical considerations in living organ donation and a new approach. An Advance-Directive Organ Registry.

Living organ donation should be recognized as an ethical compromise to the principle of nonmaleficence (doing no harm), given the risks healthy donors are allowed to assume. Living organ donation should be reserved for situations in which there is no acceptable alternative. Increasing the availability of cadaveric organs is most desirable, since it would decrease (although probably not eliminate) the need for living organ transplantation and would provide organs (ie, hearts) that could not otherwise be obtained. We propose the development of an incentive-based Advance-Directive Organ Registry, in which all adults are encouraged to register their advance directive regarding organ donations. Those individuals agreeing to permit usable organs to be taken at the time of death would receive priority for organs generated by the program, should a transplant become necessary when there is a shortage of organs. The proposed Advance-Directive Organ Registry is firmly founded on the principles of autonomy, beneficence, and justice.     

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.     

The immunological barrier in renal transplantation from living donor

Living donor kidney transplantation is uncommon in our country, mostly due to the high rate of cadaveric donation. However, such a rate has been held back in recent years and it is thought that there will be great problems in organ shortage in the next years, especially for young patients. Thus, living donation seems to be an alternative. Such a practice is particularly useful in hypersensitized patients with positive crossmatch and in ABO incompatibility. In these two cases, the waiting time for kidney transplantation goes on for many years. With the development of desensitizing protocols that employ high-dose intravenous immunoglobulins and/or plasmapheresis, together with the use of more sensitive and objective assays for immunological monitoring, patients that were not candidates for kidney transplantation in the past are now being transplanted. In the present work, immunological factors that participate in living kidney transplantation are revised, with special focus on hypersensitized patients. Available data show that living donation is a feasible alternative for future, once all the ethical problems have been solved.