Innovative strategies in living donor kidney transplantation

In an effort to increase living donor transplantation while minimizing risk and morbidity, recent advances have been made in surgical technique, kidney paired donation, desensitization, identification of living donors and research into living donor outcomes. Single-port nephrectomy and vaginal extraction have reduced donor nephrectomy incision size. Transport of live donor kidneys has reduced geographic barriers to kidney paired donation, and participation of compatible pairs and nondirected donors has increased match opportunities for incompatible pairs participating in this modality. ABO-incompatible transplantation can now be successfully performed without high-intensity immunomodulation, and HLA-incompatible transplantation has been shown in a large single-center study to provide profound survival benefit compared with waiting for a compatible donor. Complement inhibition is an exciting, emerging approach that may facilitate incompatible transplantation and treat antibody-mediated rejection. Educational and communications interventions are proving valuable in helping patients find living donors, and large studies continue to provide reassurance to carefully screened living donors that risks are very low. As living donors are critical to addressing the profound organ shortage, efforts to increase living donation remain important.     

Current status of liver transplantation in Korea]

Orthotopic liver transplantation (OLT) is now considered as a standard procedure for patients with end-stage liver disease. The number of patients listed for OLT using the brain-dead donor continues to outpace the number of OLT performed since early 1990s because the improved results of OLT had made it as a therapeutic means for irreversible liver disease. This scarcity of organs from the deceased donors has resulted in the increased use of the living donor liver grafts. Although the shortage of the brain-dead donor organs is a world-wide problem, the situation is especially serious in our country, where the deceased donor organ donation remains below 2 per million population per year. Now, Korea has the greatest need for living donor liver transplantation although it is more complex and demanding procedure than the deceased donor (whole organ) liver transplantation. Refinements of the technique and good results have rapidly established the position of the living donor liver transplantation in our country's transplant medicine. 2,345 OLTs (1,860 from the living donor and 485 from the deceased donor) were performed in 24 institutes from March 1988 to December 2004, although 5 institutes had performed more than 10 OLTs per year. Definitely, living donors represent a large pool of organs, but there might be a significant cost, mainly donor risk, to draw from this pool. To alleviate some disadvantages of the living donor liver transplantation and to provide organ to the patients who cannot find out the potential living donor from family members, recognition of necessity and nation-wide cooperative participation of organ donation after the brain-death should be propagated and encouraged in our country.     

The multiple organ donor: identification and management

Advances in surgical and immunosuppressive techniques as well as increased public awareness have made organ transplantation a well-accepted therapy. To meet the increased need for transplantable organs, medical staff need to recognize which dying patients may be suitable organ donors and how to optimally maintain that donor. We present an overview of the absolute and relative contraindications to organ donation as well as a review of the problems that may be encountered when managing organ donors and how they can best be solved. These guidelines will help increase the number of suitable organ donors and optimize the condition of the transplanted organs.     

Successful heart‐kidney transplantation from a Hepatitis C viremic donor to negative recipient: One year of follow‐up

Every year the number of patients waiting for a heart transplant increases faster than the number of available donor organs. Some potential donor organs are from donors with active communicable diseases, including hepatitis C virus (HCV), potentially making donation prohibitive. The advent of direct‐acting antiviral agents for HCV has drastically changed the treatment of HCV. Recently, these agents have been used to treat HCV in organ donor recipients who acquired the disease from the donor organ. We report a case of heart‐kidney transplantation from an HCV viremic donor to HCV negative recipient with successful treatment and sustained virologic response.     

Does the Presence of a Measurable Blood Alcohol Level in a Potential Organ Donor Affect the Outcome of Liver Transplantation?

The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty-two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty-five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/l with a mean of 0.17 g/l. Twenty-seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol-positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation.     

Increasing the Supply of Kidneys for Transplantation by Making Living Donors the Preferred Source of Donor Kidneys

At the present time, increasing the use of living donors offers the best solution to the organ shortage problem. The clinical questions raised when the first living donor kidney transplant was performed, involving donor risk, informed consent, donor protection, and organ quality, have been largely answered. We strongly encourage a wider utilization of living donation and recommend that living donation, rather than deceased donation, become the first choice for kidney transplantation.We believe that it is ethically sound to have living kidney donation as the primary source for organs when the mortality and morbidity risks to the donor are known and kept extremely low, when the donor is properly informed and protected from coercion, and when accepted national and local guidelines for living donation are followed.     

Evaluation and follow-up of living kidney donors

An increase in waiting time for a cadaveric organs and a better graft-function, graft- and patient-survival with kidneys from a living donors have lead to an increase in living-donor renal transplantation in the therapy of end-stage renal disease. In Germany, with the implementation of a transplantation law in 1997 and due to improved surgical techniques (laparoscopy) the proportion of living renal donors has almost tripled during the last five years. The transplantation law also names the potential donors, including not only genetically related but also emotionally related donors. Inclusion criteria for living donation are age > 18 years, mental ability to give consent and an altruistic motivation (exclusion of financial benefits for the donor). If ABO blood group compatibility between donor and recipient is given and a cross match does not reveal immunologic obstacles a thorough medical and psychological examination must be performed with the potential donor. All risk factors for the donor beyond the actual operation must be excluded. Therefore all organ-systems have to be evaluated and risks for the donor as well as transferable pathologies and infections must be ruled out. International guidelines help to perform an efficient evaluation. Following organ donation the donor should be medically controlled as requested by law. Also, psychological counselling should be offered. The aim is to minimize risks for the single kidney and to recognize early potentially kidney damaging affections.     

Ethical issues in transplantation: living related donation in the setting of severe neurological damage without brain death

The waiting list for renal transplantation has grown at an alarming rate over the last 2 decades, resulting in increased waiting times and deaths on the waiting list. To increase the number of available organs for transplantation, aggressive public education programs have been developed. The federal government has strengthened hospital regulations ensuring referral of all potential donors to organ recovery agencies, and living donor programs no longer limit donation to genetically related donors and recipients. We present a case that illustrates the complex ethical issues that are integral to the field of transplantation and the allocation of a scarce resource: a 50-year-old man who has a daughter with end-stage renal disease has suffered a severe cerebral vascular accident but is neither brain-dead nor a candidate for "non-heart-beating" donation. Given his poor prognosis, should the father be able to donate his kidney to the daughter in his compromised condition?     

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.     

Xenotransplantation: A potential solution to the critical organ donor shortage.

The success of allotransplantation as a treatment for end-stage organ failure has resulted in the need for an increasing number of organ donors. Attempts to meet this need include the use of organs from living related and unrelated donors, financial or other incentives for the donor family, and even the reuse of transplanted organs. Despite these initiatives, the supply of organs for transplantation still falls far short of the demand, as evidenced by longer waiting times for transplantation and decreasing transplantation rates. Even if Canada were able to increase its organ donor rate to that of Spain (40 to 50/million), where organ donation is governed by 'presumed consent' legislation, this would not alleviate the problem of donor shortage. Interest in xenotransplantation stems from the need to overcome this increasingly severe shortage of human organs. Indeed, some argue that xenotransplantation is the only potential way of addressing this shortage. As immunological barriers to xenotransplantation are better understood, those hurdles are being addressed through genetic engineering of donor animals and the development of new drug therapies. However, before xenotransplantation can be fully implemented, both the scientific/medical communities and the general public must seriously consider and attempt to resolve the many complex ethical, social and economic issues that it presents.     

Attitudes towards cadaveric organ donation--results from a representative survey of the German population

The increasing deficit of organs causes a drastic decline in the quality of life and survival of numerous patients in need of a transplantation. The purpose of this representative community study was to survey attitudes toward transplantation in the German population and to identify underlying determinants. Unlike previous surveys, fears and concerns were elicited based on a concrete case vignette. Among the 1,002 participants, 90 % were in favour of organ donation in general; 21 % reported having signed an organ donor card. Consent to organ donation was associated with younger age and higher social class; the same was true for the possession of an organ donor card. In the virtual decision situation, the majority (77 %) voted in favour of an organ donation based on saving lives, consolation for bereaved and the absence of disadvantages for the donor. Common (up to 50 %), however, were also fears and concerns regarding determination of the time of death, displacement of medical concern from the donor to the recipient of the organ, utilisation of organs for other purposes, or explantation before death. The knowledge of the determinants identified, of existing fears and concerns are helpful not only for informing the public, but also for the dialogue with the next of kin of potential donors. Here, it may be helpful not only to address arguments pro organ donation, but also to address potential fears and concerns.     

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.     

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.     

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.     

Legislating organ donation: problems with this approach

The number of organs available for transplantation in Canada is insufficient to meet the demand, so many patients die waiting for surgery. Improving the supply of donor organs by enacting legislation is controversial. Three approaches to legislation have been suggested: required request, mandated choice, and presumed consent. Required-request legislation demands that physicians ask all families of potential donors for permission to retrieve organs. Mandated choice requires all adults to register whether they wish to be organ donors. Presumed consent allows the removal of organs without permission if no choice was registered. These laws are aimed at coercion of physicians, patients and families retrospectively, but their relative success and ethics are questionable. Facilitating the organ donation process may be a better solution.     

Cardiac transplantation: the alternate list and expansion of the donor pool

PURPOSE OF REVIEW: Advances in immunosuppression and surgical techniques have allowed cardiac transplantation to become a viable option and the treatment of choice for select patients with end-stage heart failure. The success of the procedure has, however, led to a discrepancy between the number of donors available and the number of patients awaiting cardiac transplantation. As wait times for heart transplant recipients increase, nonstandard donor hearts are increasingly being used for higher risk recipients and critically ill (Status I) patients. We review the development of two recipient lists as a way to provide cardiac transplantation as an option to recipients who would be otherwise ineligible, and determine its impact on expanding the donor pool. Other methods of expanding the donor pool are also reviewed. RECENT FINDINGS: The alternate list appears to be successful in offering transplantation to patients (mostly older patients) who would not normally be eligible for this life-saving procedure. The alternate list (by changing donor organ acceptance criteria) and ongoing programs to increase organ donation have helped to expand the donor pool. SUMMARY: The donor organ shortage will continue as an increasingly older population develops end-stage organ disease. Expanding the donor pool by a variety of methods will be essential to extend the lives of these patients.     

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 Declaration of Istanbul on Organ Trafficking and Transplant Tourism

Organ commercialism, which targets vulnerable populations (such as illiterate and impoverished persons, undocumented immigrants, prisoners, and political or economic refugees) in resource-poor countries, has been condemned by international bodies such as the World Health Organization for decades. Yet in recent years, as a consequence of the increasing ease of Internet communication and the willingness of patients in rich countries to travel and purchase organs, organ trafficking and transplant tourism have grown into global problems. For example, as of 2006, foreigners received two-thirds of the 2000 kidney transplants performed annually in Pakistan.The Istanbul Declaration proclaims that the poor who sell their organs are being exploited, whether by richer people within their own countries or by transplant tourists from abroad. Moreover, transplant tourists risk physical harm by unregulated and illegal transplantation. Participants in the Istanbul Summit concluded that transplant commercialism, which targets the vulnerable, transplant tourism, and organ trafficking should be prohibited. And they also urged their fellow transplant professionals, individually and through their organizations, to put an end to these unethical activities and foster safe, accountable practices that meet the needs of transplant recipients while protecting donors.Countries from which transplant tourists originate, as well as those to which they travel to obtain transplants, are just beginning to address their respective responsibilities to protect their people from exploitation and to develop national self-sufficiency in organ donation. The Declaration should reinforce the resolve of governments and international organizations to develop laws and guidelines to bring an end to wrongful practices. “The legacy of transplantation is threatened by organ trafficking and transplant tourism. The Declaration of Istanbul aims to combat these activities and to preserve the nobility of organ donation. The success of transplantation as a life-saving treatment does not require—nor justify—victimizing the world''s poor as the source of organs for the rich” (Steering Committee of the Istanbul Summit).Organ transplantation, one of the medical miracles of the 20th century, has prolonged and improved the lives of hundreds of thousands of patients worldwide. The many great scientific and clinical advances of dedicated health professionals, as well as countless acts of generosity by organ donors and their families, have made transplantation not only a life-saving therapy but a shining symbol of human solidarity. Yet these accomplishments have been tarnished by numerous reports of trafficking in human beings who are used as sources of organs and of patient-tourists from rich countries who travel abroad to purchase organs from poor people. In 2004, the World Health Organization called on member states “to take measures to protect the poorest and vulnerable groups from transplant tourism and the sale of tissues and organs, including attention to the wider problem of international trafficking in human tissues and organs” (1).To address the urgent and growing problems of organ sales, transplant tourism, and trafficking in organ donors in the context of the global shortage of organs, a Summit Meeting of more than 150 representatives of scientific and medical bodies from around the world, government officials, social scientists, and ethicists, was held in Istanbul, Turkey, from April 30 to May 2, 2008. Preparatory work for the meeting was undertaken by a Steering Committee convened by the Transplantation Society and the International Society of Nephrology in Dubai in December 2007. That committee''s draft declaration was widely circulated and then revised in light of the comments received. At the Summit, the revised draft was reviewed by working groups and finalized in plenary deliberations.This Declaration represents the consensus of the Summit participants. All countries need a legal and professional framework to govern organ donation and transplantation activities, as well as a transparent regulatory oversight system that ensures donor and recipient safety and the enforcement of standards and prohibitions on unethical practices.Unethical practices are, in part, an undesirable consequence of the global shortage of organs for transplantation. Thus, each country should strive both to ensure that programs to prevent organ failure are implemented and to provide organs to meet the transplant needs of its residents from donors within its own population or through regional cooperation. The therapeutic potential of deceased organ donation should be maximized not only for kidneys but also for other organs, appropriate to the transplantation needs of each country. Efforts to initiate or enhance deceased donor transplantation are essential to minimize the burden on living donors. Educational programs are useful in addressing the barriers, misconceptions, and mistrust that currently impede the development of sufficient deceased donor transplantation; a successful transplant programs also depend on the existence of the relevant health system infrastructure.Access to health care is a human right but often not a reality. The provision of care for living donors before, during, and after surgery, as described in the reports of the international forums organized by the Transplantation Society in Amsterdam and Vancouver (2–4), is no less essential than taking care of the transplant recipient. A positive outcome for a recipient can never justify harm to a live donor; on the contrary, for a transplant with a live donor to be regarded as a success means that both the recipient and the donor have done well.This Declaration builds on the principles of the Universal Declaration of Human Rights (5). The broad representation at the Istanbul Summit reflects the importance of international collaboration and global consensus to improve donation and transplantation practices. The Declaration will be submitted to relevant professional organizations and to the health authorities of all countries for consideration. The legacy of transplantation must not be the impoverished victims of organ trafficking and transplant tourism but rather a celebration of the gift of health by one individual to another.     

Liver transplantation using Donation after Cardiac Death donors

The success of solid organ transplantation has brought about burgeoning waiting lists with insufficient donation rates and substantial waiting list mortality. All countries have strived to expand donor numbers beyond the standard Donation after Brain Death (DBD). This has lead to the utilization of Donation after Cardiac Death (DCD) donors, also frequently referred to as Non-Heart Beating Donors (NHBD). Organs from these donors inevitably sustain warm ischaemic damage which varies in its extent and affects early graft function as well as graft survival. As a consequence, 'non-vital' organs such as renal transplants have increased rapidly from DCD donors but more 'vital' organ transplants such as the liver have lagged behind. However, an increasing proportion of liver transplants are now derived from DCD donors. This article covers this expansion, current results, pitfalls, and steps taken to minimize complications and to improve outcome, and future developments that are likely to occur.     

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.