Kidney Transplantation And Donation

By Amir Elalouf, Phd

Much ink has been spilled about kidney transplantation. Many books have been written on the subject and examined it from multiple aspects like the medical and scientific viewpoints, the ethical, legal, and psychological standpoints, or the policy perspectives. However, unlike previous manuscripts that focused on a particular facet or feature and researched it profoundly, this book’s uniqueness is inherent in its all-encompassing nature. The novelty of this book is expressed in its comprehensiveness. It looks at kidney transplantation and donation from a bird’s-eye view to give the reader a complete and inclusive description. This book might not be as thorough or exhaustive as previous works; nevertheless, it tackles different aspects of kidney transplantation and donation and provides the reader with a broad view of the subject. To name a few, the interested reader will gain knowledge about tissue typing, system analysis, organ allocation policies and strategies, and ethical, legal, and policy issues. The book has an appeal to clinicians and the lay public alike. Though it discusses medical terms, point-system policies, or mathematical models, it presents a clear and readable version that guides the expert and the layman through the realm of organ transplantation. The book starts with illustrating the background, the problems, and the technical terms to engage the reader with the complex field of organ transplantation. After the readers are familiar with transplantation’s cornerstones, the book delves into specific issues like allocation policies and alternative proposals, vulnerable populations, community preferences, and balancing equity and efficiency. Eventually, the book comes full circle and suggests possible strategies to increase deceased donors’ supply and use. In conclusion, the book demonstrates the importance of organ transplantation policies and the need for revision and improvement without being cumbersome and tedious.

• Language: English
• Publisher: Lulu.com
• Release date: Mar 23, 2021
• ISBN: 9781678045371

Book preview

CHAPTER 1

INTRODUCTION

A brief history of transplantation

T

he advancements in organ transplantation in the last half-century represent one of medicine’s most outstanding achievements. However, the roots of this evolution (i.e., the idea of replacing diseased or damaged body parts) were planted a millennium ago (Barker and Markmann, 2013; Dangoor et al., 2015; most of the landmarks in this section have been taken from Barker and Markmann, 2013, the interested reader is directed to this text for further details).

As a technical endeavor, organ donation and transplantation have the potential to drastically improve the fate of humankind by preventing the suffering and death resulting from organ failure (Keller, 2003). This life-saving technique, which took its first significant steps at the beginning of the twentieth century, has grown exponentially, both in survival rates and the number of people on waiting lists. Scientific developments in immunosuppression and infection prevention have led to these impressive survival statistics (Svenaeus, 2010). Although the exciting and rich history of transplantation could fill several volumes, this brief overview is limited to selected ‘landmarks.’

Already, during the first decades of the twentieth century, researchers were able to establish the inevitability of homograft failure and most of the fundamental principles of transplantation immunology, such as the central role of the lymphocytes (Barker and Markmann, 2013). Alexis Carrel, a pioneer of organ grafting, is usually credited with originating vascular suturing and its use in organ transplantation. He developed the ‘triangulation technique’ for anastomosing blood vessels. However, Carrel’s accomplishments in organ grafts were not reliant on a new technique of suturing but on his use of fine needles and suture material, combined with his excellent technical skills and his obsession with strict asepsis. Most importantly, Carrel’s vast experience with organ transplants in animals made it apparent that, although autograft could often be successful, homograft could not. Carrel was also the initiator of tissue culture and organ preservation, which subsequently played a significant role in transplantation (Barker and Markmann, 2013; Dangoor et al., 2015).

The first effort to perform a human-to-human kidney transplant was attempted in 1933 by the Soviet surgeon Yu Yu Voronoy. The fact that the kidney was not procured until 6 hours after the donor’s death and was transplanted across a major blood-group mismatch accounted for the prompt failure (Barker and Markmann, 2013; Dangoor et al., 2015). During World War II, Medawar and Gibson reconfirmed the notion that homografts are destined to fail. Similar to previous investigators, they regarded this rejection as an immunological event. In the early 1950s, Billingham and Medawar established that most cows accept their twin’s graft; thus, these researchers realized that twins exchange blood in utero and that donor cell chimerism persists into adulthood. They understood that the stem cells exchanged in utero are not only for red blood cells but also for leukocytes. In conjunction with Leslie Brent, Billingham and Medawar also discovered that the induction of chimerism could prevent graft rejection (Barker and Markmann, 2013). The first successful solid organ transplant occurred on December 23, 1954, when Joseph Murray bypassed the barrier of rejection by using the patient’s identical twin as a human kidney donor. In 1955, Main and Prehn demonstrated that the weakening of the immune system by radiation allowed the induction of chimerism by inoculating bone marrow cells (Barker and Markmann, 2013).

Another pivotal development in organ transplantation was the discovery of chemical immunosuppression. In the 1950s, oncologists were assessing drugs such as nitrogen mustard and 6-MP for the treatment of malignancies. In 1959-1960, interest was drawn to using these drugs (combined with their derivative azathioprine) in transplantation. As a result of these developments, in 1963, one of the most significant landmarks in the history of transplantation, which completely changed the outlook for renal transplantation, in particular, was discovered. Starzl devised a new immunosuppressive protocol that resulted in more than 70% of patients achieving one-year renal graft survival.  Starzl’s novel contribution was to add prednisone to azathioprine (Barker and Markmann, 2013).

The period 1964–1980 can be considered as a phase of consolidation or plateau. During this time, besides the development of antilymphocytic serum, no significant landmarks can be identified. Nevertheless, steady progress was observed. The practical innovations and accomplishments through this period included: availability of dialysis, antibody screening to avoid hyperacute rejection, understanding of the significance of tissue typing for related donor transplants, acknowledgment of brain death, ex-vivo preservation, enabling donor organs to be transported and shared, and, possibly most significantly, the accumulation of experience in patient management that led to the prevention of over-immunosuppression, thus lowering subsequent infections and deaths (Barker and Markmann, 2013).

The next landmark in the history of transplantation was the discovery of the ‘wonder drug’ cyclosporine. Cyclosporine revolutionized transplantation by significantly improving kidney transplant outcomes and enabling successful extrarenal transplants (Calne, 2006; Watson and Dark, 2012; Barker and Markmann, 2013). This drug constituted the standard baseline immunosuppressant until 1989, when Tacrolimus replaced it. Notably, the Tacrolimus–FKBP12 complex binds to a different site on calcineurin to achieve a similar effect as cyclosporine. It is stronger than cyclosporine and has proven superiority in most organ transplantation forms (Watson and Dark, 2012). To conclude, modern immunosuppression protocols with agents such as cyclosporine/tacrolimus and T-cell antibodies result in remarkable short- and mid-term survival rates, with one-year survival exceeding 90% for kidney allografts (Barker and Markmann, 2013).

In summary, organ transplantation is a story of extraordinary achievements as well as ongoing challenges. Over the last century, organ transplantation has overcome many technical limitations and medical boundaries. The advances, innovations, and breakthroughs have included the development of techniques for vascular anastomosis, management of the immune response (originally by evading it through the use of identical twins and then regulating it with chemical immunosuppressants), and the invention of preservation solutions that allow prolonged periods of ex-vivo storage while preserving function. However, two prominent challenges remain: one relates to immunosuppression, which needs to be improved to extend the grafts’ life, and the second, which has existed from the outset, is to overcome the shortage of suitable donor organs (Watson and Dark, 2012).

The organ shortage

Organs for transplantation are a scarce resource. Markedly, there is a stark disparity between the number of patients awaiting deceased-donor organ transplants and the rate at which organs become available. Hence, the current reality is an increasing gap between supply and demand for organs for transplantation. It is suggested that the main reasons for organ shortage can be attributed to the scarcity of registered donors, eligibility criteria that preclude donation (e.g., fewer people died in circumstances in which organ donation is feasible), lack of improvement of the consent rate to deceased organ donation, and generally, lack of resources to address these concerns. Scarcity in organs is also a byproduct of expectations created due to scientific and technological progress in organ procurement and transplantation. There is an increasing prevalence of end-stage organ failure in the modern world, which is associated with an aging population with a higher incidence of comorbidities like diabetes and hypertension.

Furthermore, medical advances in retrieval, transplantation, and immunotherapy methods have significantly increased the probability of successful organ transplants for patients who previously would not have been considered eligible for transplantation. These progress outcomes have added to the already existing gap between supply and demand for organs (Farrell, 2015). Therefore, given these points, and in response to sensitivity to ethical concerns, laws and policies administrating the use of organs for transplantation are rapidly evolving and becoming increasingly detailed and complex (Price, 2012).

Academic research and policy debates have deliberated about the best way to address chronic organ shortage. They strive to find the optimal approach to balance the competing needs of increasing the availability of organs for transplantation and respecting the rights of donors, recipients, and their families. Such discussion has chiefly focused on which strategies and actions should be implemented to increase both living and deceased organ donation, underpinned by an improved comprehension of donor motivation (Farrell, 2015).

The premise is that the problem of organ shortage is a complex and disputed field of public policy, which necessitates the consideration and weighing of several key issues such as the ethical principles that should underpin donation, the strategies that ought to be employed to increase donation rates, and the best methods to enhance the legitimacy of the organ donation and transplantation system (Farrell, 2015). Numerous legislative and social changes have been suggested or implemented to address the critical organ shortage and increase the number of registered organ donors. To name a few, these have included presumed consent donation (which will be discussed in detail in the next section), the gift relationship, incentivized organ donation, commercial organ transplantation, mandated choice models, and educational programs.

Possible strategies to increase organ donation

The gift relationship

Many countries implement the gift relationship as the central ethical principle sustaining the donor-recipient bond in human tissue donation (Brawer Ben-David, 2005; Moorlock, Ives, and Draper, 2014). This principle’s popularity and pervasiveness stem from the notion of an altruistic donation without expectation of financial or other rewards. This altruistic motivation can be perceived as a vital part of the social contract around which a particular society is organized (Farrell, 2015).

Incentivizing donation

Academic and policy disputes contemplated the best methods to increase rates of organ donation, and primarily the use of financial reward in the form of direct monetary payment, sale of organs, compensation (e.g., cost of funeral expenses for deceased organ donors), reimbursement (fees and lost wages incurred by living organ donors) or other indirect means. However, financial incentives have been mostly criticized on an ethical basis. On the one hand, it has been claimed that monetary payment is ethically justified since it might diminish the gap between supply and demand and lower the rate of patients with end-stage renal disease languishing for years and/or dying while on waiting lists. Furthermore, a just ethical approach should include acknowledging an autonomous choice to donate even in the face of socioeconomic deprivation. Additionally, differing cultural values surrounding organ donation may make financial payment more acceptable, especially in living organ donation (Farrell, 2015). On the other hand, it has been vehemently argued that the use of financial incentives is ethically problematic due to their potential negative impact on the altruistic motivation to donate, the exclusion to commodify the body, and the substantial potential for donor harm and exploitation. Financial incentives can also serve to ingrain power, wealth, and race disparities, with poor donors being exploited by a wealthier recipient population (Farrell, 2015).

It is noteworthy that incentives to donate organs do not have to be financial and may take different forms. They can comprise recognition that is valued by the donor, such as ‘benefits-in-kind’ or ‘benefit sharing’ of being granted priority in organ allocation (Farrell, 2015).

Except for Iran, direct financial payment for organs as an incentivization strategy has not enticed extensive political or public support. Therefore, the emphasis has shifted towards removing financial disincentives to organ donation (Wiseman, 2012). For example, proposals for payment for funeral expenses to families who consented to donate organs or reimbursement for time off work and related costs associated with undergoing and recovering from surgery to remove organs (Farrell, 2015).

Commercial organ transplants

Overwhelmingly the sale of organs for transplantation has been perceived as unethical. Hence, Iran remains the only country in the world to implement a sustained, bureaucratically organized, state-sponsored system of financial compensation for kidneys from living unrelated donors (Tober, 2007). Iran has legalized a living, non-related donation of kidneys and established an associated transplantation system (Major, 2008). As a strategy to broaden organ transplantation, the Iranian government initiated the ‘organ donation reward’ scheme. According to this government-organized system that regulates and funds the transplantation process, a reward is granted as a gift from the government to acknowledge altruistic living organ donation. The reward aims to somewhat compensate the donor for the damage incurred and prevent a financial link between the recipient and the donor (Kiani et al., 2018).

Supporters of the Iranian model insist that this policy eliminated waiting time and showed no significant variances in groups of donors and recipients in terms of socioeconomic background (e.g., wealth and education level) (Griffin, 2007). They stress that the Iranian government did not avert the brain death donation program’s development and progression. Contrarily, it has devoted substantial budgets through funding hospitals and staff to support the brain death donation program or redirected part of the grant of living unrelated renal donation to advance it (Mahdavi-Mazde, 2012). Adversaries maintain that the system is not as perfect as it might seem. There is evidence to suggest that the system has not cleared its waiting list and that trading between socioeconomic classes still poses a significant problem (Griffin, 2007). Moreover, it is possible that unrelated living donors constitute the majority of donations due to donors’ financial incentives and poverty or unemployment as well as owing to this system’s aggressive promotion over cadaveric donation (Tober, 2007). Additionally, critics argue that organs and human tissues’ commodification depersonalize and devalue the human body (Matas, 2004). With that said, policymakers can and should draw lessons from the existing experiences involving payments and incentives. Specifically, legislators ought to find techniques to remove disincentives and barriers such as loss of income and reimbursement of expenses for those who agree to donate their organs. Nonetheless, findings show a minimal effect of tax benefits and paid leave policies on the solid-organ donation (Venkataramani et al., 2012; Chatterjee et al., 2015).

Models of consent

The dilemma of which model of consent will produce the most significant increase in organ donation rates constitutes a recurring theme in the field. The question of whether opt-in or opt-out systems will increase support for organ donation perplexes researchers and legislators alike. While the meaning and implication of these opt-in/opt-out systems will be discussed in detail in the next section, this paragraph will deliberate on a third strategy- mandated choice. The mandated choice strategy necessitates individuals to document their wishes regarding organ donation after death at some point in their lives. In other words, mandated choice allows organ donors to make considered decisions about their intentions to donate organs. It requires individuals to formally indicate whether they wish to be organ donors in the event of their death. Notably, people are free to choose to donate, not donate or defer the decision to their relatives. However, as the name implies, it is compulsory to make a decision, with the stated choice being potentially revocable (Price, 2012; Shanmugarajah et al., 2014; Farrell, 2015). The mandated choice’s fundamental assumption is that as a bulk of individuals assert themselves to favor organ donation after death and declare willingness to donate their organs, a majority will ‘sign up’ as donors (Price, 2012).

Similar to previous strategies, mandated choice is being criticized for compelling people to make a decision on organ donation, thus undermining an individual's autonomy. Yet, supporters claim that this model essentially stimulates autonomy by guaranteeing that a person’s preference is sustained after death rather than letting relatives overrule the deceased’s wishes (Chouhan and Draper, 2003).

Educational programs

Education of the public through the media and the education system (e.g., schools, universities, and other pedagogic institutions), combined with suitable training programs for hospital and ICU staff, have proven efficient and resulted in a substantial organ donation increase (Abouna, 2008).

This section offered an outline of