Living Organ Donation Research Articles

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Reinforcing Global Oversight of Organ Transplantation: Activity and Outcome Monitoring Through the Development of Registries.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Improving long-term kidney allograft survival by rethinking HLA compatibility: from molecular matching to non-HLA genes.

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and post-transplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation.

Public Acceptance of Living Donor Liver Transplant for Colorectal Liver Metastases: A Web-Based Survey.

Recent advancements in cancer treatment and post-transplant management have expanded the population of living donor liver transplant (LDLT) candidates. We aimed to examine variations in public acceptance of LDLT based on patient diagnosis, including unresectable colorectal liver metastases (uCRLM). A web-based survey collected demographic information and general perceptions about organ donation in different settings. Respondents indicated their likelihood of being a living liver donor for a family member with genetic liver disease, alcohol-related liver disease (ALD), and uCRLM. Differences in the likelihood of donation between scenarios were compared. There were 491 survey respondents (female [76.5%], Caucasians [87.4%], and had at least a college degree [98.2%]). Most (82.4%) were aware of the option of living liver donation before the study and 95% supported living organ donation in general. Over 80% were registered as organ donors. Ninety percent indicated that they would be likely to donate to a family member with a genetic liver disease if they qualified as a living donor; significantly more than ALD (59%) and uCRLM (71%) (p < 0.001). Willingness to donate to patients with uCRLM was significantly higher (p < 0.001) than the hypothetical patient with ALD with a clinically accepted recovery period of 6 months. This study is the first of its kind to assess thepublic acceptance of living liver donation for uCRLM. Respondents were as or more supportive of donating to uCRLM as they were of generally accepted indications for LT. Further surveys with a broader respondent pool are warranted.

Challenges and Possible Solutions to Pediatric Organ Donation and Transplantation in Turkey and the Middle East: Panel Discussion/Brainstorm Session Summary Report.

Organ transplantation is the best therapeutic option for children with end-stage organ failure. Pediatric transplantation centers and prioritization of organs for children are being established around the world. However, there is an important discrepancy observed when comparing high-income countries versus low-income and middle-income countries, as programs are active in some, but not in many others. Deceased organ donation is low in many places, which has led to an increase of organ shortage; consequently, there is a need to rely on the use of living donor organs. This is frequently the case for pediatric transplantation. To gather information about the possible reasons underlying these challenges and to propose possible solutions, a brainstorming session took place during the International Symposium on Pediatric Organ Donation and Transplantation in Ankara, Turkey. A description on different topics that were discussed is presented herein.

Abstract A057: Investigating Fibroblast-Epithelial crosstalk in pre-malignant and cancerous microenvironment

Abstract Pancreatic ductal adenocarcinoma (PDAC) originates from precursor lesions, the most common of which are known as pancreatic intraepithelial neoplasia (PanIN). PanIN formation and progression is accompanied by accumulation of a precursor microenvironment (PME) composed of desmoplastic stroma that plays an important role in promoting tumor growth and immune evasion. The crosstalk between tumor cells and stromal cells is an area of active investigation. While PanIN and the PME have been extensively studied in mouse models, their nature in humans have remained elusive as there is no clinical indication to sample healthy pancreas. Through a unique collaboration with the Gift of Life Organ and Tissue donation program, we performed transcriptomic analysis on normal pancreata declined for transplant. We noted that epithelial cells in the PanIN and cancer microenvironment were transcriptomically similar; however, their surrounding stromal fibroblasts were markedly distinct. Given that most precursor lesions remain quiescent while some progress to tumor, we sought out to elucidate how the transcriptional programs in epithelial cells influence fibroblast cell fate. To do so, we developed a 3D ex-vivo organoid-fibroblast coculture system using primary organoid and fibroblast cultures successfully derived from Gift of Life pancreata or PDAC patients undergoing surgical resection. Our coculture system retains histological features of heterogeneity observed in vivo. Using single cell RNA-sequencing analysis of matched fibroblast-organoid cocultures we identified factors that were highly expressed in fibroblasts in tumor cocultures, but not in normal cocultures. We are currently interrogating candidate ligand/receptor interactions in our cocultures to determine the mediators of this epithelial-mediated fibroblast polarization. This model will allow us to gain an understanding about how components of the microenvironment restrain or promote malignant transformation and serve as a great tool to study therapies targeting tumor and stromal cells in a patient specific manner. Citation Format: Padma Kadiyala, Ahmed Elhossiny, Jianhua Liu, Alexander Bray, Katelyn Donahue, Arvind Rao, Jiaqi Shi, Yaqing Zhang, Filip Bednar, Timothy Frankel, Eileen Carpenter, Marina Pasca Di Magliano. Investigating Fibroblast-Epithelial crosstalk in pre-malignant and cancerous microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A057.

341.3: Dramatic increase in repeat living organ donation.

341.3: Dramatic increase in repeat living organ donation.

How Do Financial Obstacles Affect Decision-Making Among Potential Living Organ Donors?

Introduction: Living donation increases the organ supply, but associated non-medical expenses can disincentivize donation. Programs aimed at increasing living donation need to better understand how financial obstacles, including lost wages, impact the decision to pursue donation. Methods/Approach: Forty-eight interviews were conducted and analyzed using a grounded theory approach. Findings: Three key themes were identified that influenced decision-making: emotional attachment, temporal flexibility, and job security. These themes emerged when dividing interview participants into 3 groups: close relationship donors, broader network donors, and non-directed donors, representing donation to a family member or friend, a specific person they do not know well or at all, or a non-specified individual, respectively. Most close relationship donors wanted to donate regardless of personal financial cost, based on emotional attachment to the recipient. Wage reimbursement did not typically affect their decision-making but could reduce stress. Since non-directed donors did not donate to a specific individual, they could wait to achieve financial stability before donating, if needed. While wage reimbursement might create more proximate stability, non-directed donors had the flexibility to postpone donations until they could independently achieve financial stability. Lacking emotional attachment and temporal flexibility, broader network donors were particularly active decision-makers and most influenced by wage reimbursement. Across all groups, donors with job security were more resolute about donating. Conclusion: The findings underscore the importance of lost wage reimbursement to facilitate donation and reduce stress, and policies to protect donor job security.

403.2: Project donor: A national intervention to improve the health of living organ donors.

403.2: Project donor: A national intervention to improve the health of living organ donors.

Organ Markets, Options, and an Over-Inclusiveness Objection: On Rippon's Argument.

Human organs available for transplant are in short supply. One way to increase the supply of organs consists in legalizing a live donor market. Such a market is, however, controversial. This article is about an objection to live donor organ markets made by Simon Rippon. Rippon's objection is that the presence of a market option creates new social and legal pressures that harm the poor. Legalizing the option of selling your organs transforms into a harmful, and morally indefensible, social, and legal pressure to sell on the financially desperate. This article defends the conclusion that Rippon's argument fails as an objection to live donor organ markets. It fails because it has implausibly expansive implications about which markets are morally problematic. In short, Rippon's argument proves too much. Sections one and two introduce Rippon's argument. Sections three and four contain the argument against Rippon. The main argumentative move is that the features of an organ market that, according to Rippon, justify a ban on such a market are features that also characterize several other markets that are normally considered unproblematic, for example, markets where individuals sell their labour abroad in jobs that are dangerous. So, if an organ market should be legally impermissible, so should these labour markets. Section five considers several objections to the argument against Rippon. It is argued that these objections fail. Section six is a conclusion that sums up the findings of the article.

Ethics of abortion in transplantation.

The controversial medical procedure of abortion is the subject of this article. It argues that for transplant patients, including recipients, abortion is ethical. In June 2022, the United States Supreme Court overturned the long-standing decision of Roe v. Wade. This decision has led to a socio-legal environment where obtaining an abortion is impossible for some patients. However, the moral position relating to patients who have undergone transplants or are on a waiting list has been largely overlooked. End-stage renal, liver, and heart disease presents a hazardous situation for pregnancy, posing risks to both the fetus and the pregnant person. The abortion procedure is medically safer and allows a patient to proceed with a transplant. Limiting access to abortion or preventing it altogether will have a significant negative impact on transplant patients. The ethical analysis of abortion can be likened to compelling a relative or loved one of a transplant recipient to donate an organ to their family member or loved one. This article emphasizes the importance of maintaining the legal availability of abortion for transplant patients. Allowing abortions in transplant patients upholds ethical parity, as seen in the analogous situation of live organ donation.

Healthcare Worker Attitudes to Living Donation Prior to Planned Withdrawal of Care.

This study assesses the attitudes of healthcare practitioners toward Living Donation Prior to Planned Withdrawal of Care (LD-PPW): the recovery of a living donor organ before withdrawal of life-sustaining measures in a patient who does not meet criteria for brain death, but for whom medical care toward meaningful recovery is deemed futile. An electronic survey was administered to 1735 members of the American Society of Transplant Surgeons mailing list with 187 responses (10.8%). Data from this study revealed that 70% of responding practitioners agreed with LD-PPW due to principles of beneficence and autonomy. Also, 65% of participants felt confident in their ability to declare the futility of care and 70% felt that LD-PPW should be added as an option when registering to become an organ donor. Currently, nearly half of all donation after circulatory determination of death do not proceed to donation. LD-PPW has been proposed as an alternative procedure targeted at increasing the quality and quantity of transplantable organs while respecting the donor's right to donate, though its implementation has been hindered by concerns over public and provider perception. This study revealed support for LD-PPW among healthcare practitioners as an alternative procedure to increase the quality and quantity of transplantable organs while respecting the donor's right to donate.

Family-Oriented Living Organ Donation in Bangladesh: A Bioethical Defence.

This study focuses on issues related to living organ donation for transplantation in Bangladesh. The policy and practice of living organ donation for transplantation in Bangladesh is family-oriented: close relatives (legal and genetic) are the only ones allowed to be living donors. Unrelated donors, altruistic donors (directed and non-directed), and paired/pooled or non-directed altruistic living donor chains-as many of these are implemented in other countries-are not legally allowed to serve as living donors in Bangladesh. This paper presents normative arguments explaining why the family-oriented nature of regulations and practices surrounding living organ donation for transplantation is essential for Bangladesh. In this article, I specifically argue that if the Bangladesh government revises the current biomedical policy robustly beyond relatives and allows unrelated donors to donate organs legally, this may foster organ selling due to the poverty and corruption problems in Bangladesh. The family-oriented requirement of the living organ donation policy and practice is defensible and morally justifiable as it preserves common notions of the family unit and family bonding in Bangladesh. Maintaining the current living-donation regulations and promoting deceased donation is the way forward, as this safely preserves the family values, protects against organ selling, and increases access to organ transplantation.

Organ Utilization From Donors Following Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review of Graft and Recipient Outcome.

The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR. We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024. From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%). Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool.

Living Donor Decision-Making and the Complex Interplay of Finances and Other Motivators, Barriers, and Facilitators.

The decision to become a living donor requires consideration of a complex, interactive array of factors that could be targeted for clinical, policy, and educational interventions. Our objective was to assess how financial barriers interact with motivators, other barriers, and facilitators during this process. Data were obtained from a public survey assessing motivators, barriers, and facilitators of living donation. We used multivariable logistic regression and consensus k-means clustering to assess interactions between financial concerns and other considerations in the decision-making process. Among 1592 respondents, the average age was 43; 74% were female and 14% and 6% identified as Hispanic and Black, respectively. Among employed respondents (72%), 40% indicated that they would not be able to donate without lost wage reimbursement. Stronger agreement with worries about expenses and dependent care challenges was associated with not being able to donate without lost wage reimbursement (OR=1.2, 95% CI=1.0-1.3; OR=1.2, 95% CI=1.1-1.3, respectively). Four respondent clusters were identified. Cluster 1 had strong motivators and facilitators with minimal barriers. Cluster 2 had barriers related to health concerns, nervousness, and dependent care. Clusters 3 and 4 had financial barriers. Cluster 3 also had anxiety related to surgery and dependent care. Financial barriers interact primarily with health and dependent care concerns when considering living organ donation. Targeted interventions to reduce financial barriers and improve provider communication regarding donation-related risks are needed.

Fueling the success of transplantation through nutrition: recent insights into nutritional interventions, their interplay with gut microbiota and cellular mechanisms.

The role of nutrition in organ health including solid organ transplantation is broadly accepted, but robust data on nutritional regimens remains scarce calling for further investigation of specific dietary approaches at the different stages of organ transplantation. This review gives an update on the latest insights into nutritional interventions highlighting the potential of specific dietary regimens prior to transplantation aiming for organ protection and the interplay between dietary intake and gut microbiota. Nutrition holds the potential to optimize patients' health prior to and after surgery, it may enhance patients' ability to cope with the procedure-associated stress and it may accelerate their recovery from surgery. Nutrition helps to reduce morbidity and mortality in addition to preserve graft function. In the case of living organ donation, dietary preconditioning strategies promise novel approaches to limit ischemic organ damage during transplantation and to identify the underlying molecular mechanisms of diet-induced organ protection. Functioning gut microbiota are required to limit systemic inflammation and to generate protective metabolites such as short-chain fatty acids or hydrogen sulfide. Nutritional intervention is a promising therapeutic concept including the pre- and rehabilitation stage in order to improve the recipients' outcome after solid organ transplantation.

Organ donation and HIV: Awareness and willingness to be a living donor among people with HIV in Uganda.

HIV+-to-HIV+ organ transplantation has demonstrated promise and is now authorized for research purposes in certain countries. However, organ transplantation is dependent on the availability of organ donors. We assessed the awareness and willingness to donate organs among people with HIV (PWH) in Uganda. We conducted a multicenter cross-sectional study between October 2023 and January 2024 in four large HIV clinics in Northern Uganda. The study population consisted of PWH. A structured questionnaire was used to collect data regarding awareness, willingness, and beliefs regarding organ donation. Organ donation was defined as the willingness to be a living donor of a solid organ. We conducted multivariable logistic regression to assess for an association between willingness to donate organs and selected exposures. Data were analyzed in Stata version 15.0. Results are expressed as adjusted odds ratio (AOR) with 95% confidence intervals (CI). A total of 232 participants were recruited. The mean age ± standard deviation of the participants was 42.2±11.8 years. All participants were on antiretroviral therapy. Sixty-two (26.7%) had a CD4 count less than or equal to 200 cells/mm3. The majority (80.6%, n = 187) had ever heard of organ donation. Slightly more than a third (34.9%, n = 81) were willing to donate organs. Factors associated with willingness to be a living organ donor included being female (AOR: 1.56; 95% CI: 1.15-2.11), having a tertiary education level (AOR: 1.79; 95% CI: 1.03-3.11), average monthly income >500000 UGX (135.1USD) (AOR: 5.5; 95% CI: 1.97-15.40), ever heard about organ donation (AOR: 5.4; 95% CI: 1.67-17.8), and attending an organ donation campaign (AOR: 2.0; 95% CI: 1.07-3.74). Awareness about organ donation was high but the willingness to be a living organ donor was low among PWH in Uganda. There is a need to sensitize the community about the need and benefits of organ donation with the involvement of media and the healthcare workers.

Laparoscopic Right Donor Nephrectomy: A Two-Center Comparative Study.

Introduction As the field of laparoscopic living donor nephrectomy (LLDN) has progressed over the years, there has been a growing emphasis on optimizing surgical techniques and outcomes to ensure the safety and well-being of living kidney donors. The early experiences with right LLDN, marked by challenges and concerns such as high conversion rates to open surgery and early graft loss due to technical reasons, prompted a reevaluation of the approach towardright-sided donor nephrectomies. In this article, we aim to compare the safety and efficacy of right LLDNto left LLDN performed in our centers and to provide valuable insights that can ultimately enhance patient outcomes and ensure the well-being of living organ donors. Methods Between January 2018 and January 2022, we conducted 16 cases of right LLDNand compared them with 134 cases of left LLDN procedures done in the Kingdom of Bahrain and Jordan over the same time period. We analyzed differences in donor age, sex, operative time, warm ischemia time (WIT), graft function, complications, and conversion to open technique. Patient data and surgical outcomes were extracted from medical records and surgical databases. Statistical analysis was conducted to identify significant differences between the two groups. Categorical variables such as complications and safety outcomes were compared using chi-square tests and logistic regression analysis. The primary outcomes of interest included safety metrics such as complication rates, vascular complications, graft loss, and postoperative serum creatinine levels for the recipients. Results Our study showed similar demographics in both groups. However, the operative time was shorter for the left LLDN, with 81 minutes compared to 96 minutes for the right. Warm ischemia times (WITs) were comparable at 4.5 minutes for the left and 5.2 minutes for the right. There was less incidence of delayed graft function on the left side (none in the left group compared to one case in the right group). Both groups had similar six-month graft function in terms of serum creatinine levels (0.98 mg/dL for the left and 1.2 mg/dL for the right), hospital stays (2.5 days for the left and 2.8 days for the right), and estimated blood loss (EBL) (90 mL for the left and 50 mL for the right). Additionally, no blood transfusions were required in either group, but there was one case of conversion to open surgery in the right LLDN group. Conclusion Our data confirm the safety and efficacy of the right LLDN, consistent with the current literature. This increases the cumulative evidence supporting the use of laparoscopic retrieval on the right side when indicated.

Another Defense of Abortion: What Transplant Ethics Tells Us about the Ethics of Abortion after Dobbs.

In 1971, two years before Roe v. Wade affirmed federal protection for abortion, Judith Jarvis Thomson attempted to demonstrate the wrongs of forced gestation through analogy: you awake to find that the world's most esteemed violinist is wholly, physically dependent on you for life support. Here, the authors suggest that Thomson's intuition, that there is a relevant similarity between providing living kidney support and forced gestation, is realized in the contemporary practice of living organ donation. After detailing the robust analogy between living kidney donation and gestation, we turn to current ethical guidelines incorporated in the United Network for Organ Sharing's requirements for legally authorized organ donation and transplantation. We conclude that if, as we-and Thomson-suggest, organ donation and gestation are relevantly similar, then the ethical framework supporting donation may aid in articulating ethical grounds that will be compelling in informing the legal grounds for a defense of abortion.

Public Opinions on Removing Disincentives and Introducing Incentives for Organ Donation: Proposing a European Research Agenda.

The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs. It is important to understand not only the ethical acceptability of (dis)incentives for organ donation, but also its societal acceptance. In this review, we propose a research agenda to help guide future empirical studies on public preferences in Europe towards the removal of disincentives and introduction of incentives for organ donation. We first present a systematic literature review on public opinions concerning (financial) (dis)incentives for organ donation in European countries. Next, we describe the results of a randomized survey experiment conducted in the United States. This experiment is crucial because it suggests that societal support for incentivizing organ donation depends on the specific features and institutional design of the proposed incentive scheme. We conclude by proposing this experiment's framework as a blueprint for European research on this topic.