Financial, policy, and ethical barriers to the expansion of living donor liver transplant: Meeting report from a living donor liver transplant consensus conference.

INTRODUCTION: In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US). METHODS: A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers. RESULTS: Living liver donors endure multiple obstacles including financial instability, loss of job security, and potential morbidity. These concerns, along with other center, state, and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion. CONCLUSION: Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT.

Examining post-donation outcomes in Hispanic/Latinx living kidney donors in the United States: A systematic review.

We conducted a systematic review to assess outcomes in Hispanic donors and explore how Hispanic ethnicity was characterized. We searched PubMed, EMBASE, and Scopus through October 2021. Two reviewers independently screened study titles, abstracts, and full texts; they also qualitatively synthesized results and independently assessed quality of included studies. Eighteen studies met our inclusion criteria. Study sample sizes ranged from 4007 to 143,750 donors and mean age ranged from 37 to 54 years. Maximum follow-up time of studies varied from a perioperative donor nephrectomy period to 30 years post-donation. Hispanic donors ranged between 6% and 21% of the donor populations across studies. Most studies reported Hispanic ethnicity under race or a combined race and ethnicity category. Compared to non-Hispanic White donors, Hispanic donors were not at increased risk for post-donation mortality, end-stage kidney disease, cardiovascular disease, non-pregnancy-related hospitalizations, or overall perioperative surgical complications. Compared to non-Hispanic White donors, most studies showed Hispanic donors were at higher risk for diabetes mellitus following nephrectomy; however, mixed findings were seen regarding the risk for post-donation chronic kidney disease and hypertension. Future studies should evaluate cultural, socioeconomic, and geographic differences within the heterogeneous Hispanic donor population, which may further explain variation in health outcomes.

A regulated system of incentives for living kidney donation: Clearing the way for an informed assessment.

The kidney shortage continues to be a crisis for our patients. Despite numerous attempts to increase living and deceased donation, annually in the United States, thousands of candidates are removed from the kidney transplant waiting list because of either death or becoming too sick to transplant. To increase living donation, trials of a regulated system of incentives for living donation have been proposed. Such trials may show: (1) a significant increase in donation, and (2) that informed, incentivized donors, making an autonomous decision to donate, have the same medical and psychosocial outcomes as our conventional donors. Given the stakes, the proposal warrants careful consideration. However, to date, much discussion of the proposal has been unproductive. Objections commonly leveled against it: fail to engage with it; conflate it with underground, unregulated markets; speculate without evidence; and reason fallaciously, favoring rhetorical impact over logic. The present paper is a corrective. It identifies these common errors so they are not repeated, thus allowing space for an assessment of the proposal on its merits.

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants.

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m2 ) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.

Donor-reported barriers to living kidney donor follow-up.

BACKGROUND: Despite regulations mandating follow-up laboratory testing for living kidney donors, less than half of transplant centers are in compliance. We sought to understand barriers to follow-up testing from the donors' perspective. METHODS: We surveyed our center's living kidney donors. Binary logistic regression was used to assess factors associated with follow-up testing completion. RESULTS: Of 185 living kidney donors, 110 (59.4%) participated. Among them, 82 (74.5%) completed 6-month laboratory testing, 76 (69.1%) completed 12-month testing, 68 (61.8%) completed both, and 21 (19.0%) completed neither. Six-month testing completion was strongly associated with 12-month testing completion (OR 9.74, 95%CI: 2.23-42.50; p = .002). Those who disagreed with the statements, "Getting labs checked wasn't a priority for me," (OR for completing 6-month testing: 15.05, 95%CI: 3.70-61.18; p < .001; OR for completing 12-month testing: 5.85, 95%CI: 1.94-17.63; p = .002); and, "I forgot to get labs drawn [until I was reminded]" (OR for completing 6-month testing: 6.93, 95%CI: 1.59-30.08; p = .01; OR for completing 12-month testing: 6.55, 95%CI: 1.98-21.63; p = .002) were more likely to complete testing. CONCLUSIONS: To our knowledge, this is the only study providing perspective on donor insights regarding the need for follow-up testing post donation. Interventions to influence living donor attitudes toward follow-up testing may improve follow-up.

Health-related quality of life after anonymous nondirected living liver donation: A multicenter collaboration.

Literature on living nondirected liver donation is sparse. The purpose of this study was to assess health-related quality of life (HR-QOL) in anonymous nondirected living liver donors (ND-LLDs). ND-LLDs at 3 centers: University of Alberta (n = 12), University of Colorado (n = 12), and University of Southern California (n = 12), were surveyed. Thirty donors (83%) responded to the Donor Quality of Life (USC DQLS) and Short-Form 36 (SF-36). Most respondents (n = 15, 50%) donated their left lateral segment, 27% right lobe, and 23% left lobe. The majority were female (67%) and mean age was 38.9 ± 11.2 years at donation. Median follow-up was 1.1 (interquartile range 0.4-3.3) years. Approximately 37% had previously donated a kidney. Eleven experienced ≥1 postoperative complication, with only 1 Clavien-Dindo IIIb. Most reported minimal impact on school or work performance, all felt positive or neutral about their overall health since donation, and none expressed postdonation regrets. No donor reported impacts on health insurability, and 3 of 4 respondents attempting to purchase life insurance postdonation were successful. ND-LLD SF-36 outcomes were similar to US population norms. Overall, ND-LLDs demonstrated acceptable HR-QOL after donation and are appropriate candidates for partial liver donation. Based on evaluation of donation impact, consideration should be given to postdonation support strategies.

Living donor liver paired exchange: A North American first.

Paired organ exchange can be used to circumvent living donor-recipient ABO incompatibilities. Herein, we present the first case of successful liver paired exchange in North America. This 2-way swap required 4 simultaneous operations: 2 living donor hepatectomies and 2 living donor liver transplants. A nondirected anonymous living donor gift initiated this domino exchange, alleviating an ABO incompatibility in the other donor-recipient pair. With careful attention to ethical and logistical issues, paired liver exchange is a feasible option to expand the donor pool for incompatible living liver donor-recipient pairs.

Ensuring the need is met: A 50-year simulation study of the National Kidney Registry's family voucher program.

The National Kidney Registry (NKR) Advanced Donation Program enables living donors the opportunity to donate altruistically, or in advance of a potential recipient's transplant, and to receive a voucher that can be redeemed for a future transplant facilitated by the NKR. Family vouchers allow a donor to identify multiple individuals within their immediate family, with the first person in that group in need of a transplant being prioritized to receive a kidney. An increase in vouchers introduces concerns that demand for future voucher redemptions could exceed the supply of available donors and kidneys. A Monte Carlo simulation model was constructed to estimate the annual number of voucher redemptions relative to the number of kidneys available over a 50-year time horizon under several projected scenarios for growth of the program. In all simulated scenarios, the number of available kidneys exceeded voucher redemptions every year. While not able to account for all real-life scenarios, this simulation study found that the NKR should be able to satisfy the likely redemption of increasing numbers of vouchers under a range of possible scenarios over a 50-year time horizon. This modeling exercise suggests that a donor family's future needs can be satisfied through the voucher program.

Understanding family dynamics in adult-to-adult living donor liver transplantation decision-making in Taiwan: Motivation, communication, and ambivalence.

This study investigated how multiple family members co-construct the ethical significance of living donor liver transplantation (LDLT) and how the family structure and dynamics of donor-recipient-caregiver relationships shape the communication and decision-making process within the sociocultural context of Taiwan. We conducted in-depth interviews with 36 participants from 13 families at the Chang Gung Memorial Hospital from February to December 2019. Interviews were audio recorded, transcribed, and translated from Mandarin to English and analyzed utilizing grounded theory and thematic analysis. Our findings revealed that LDLT in Taiwan is not merely a personal choice of either donor or recipient but essentially a collaborative process of family-centered medical decision-making, intertwined with socioeconomic conditions, cultural and social norms, gender roles, and the division of labor in the household. The notion of reciprocity and indebtedness for family members is a central theme underlying the entire process of motivation, deliberation, and decision-making, thereby reinforcing the naturalness of LDLT. However, our study highlighted that donors from families with traditional gender hierarchy and power imbalance may experience psychological and social vulnerabilities. Conclusively, we suggest that healthcare professionals should be sensitive to the contextual and relational factors involved in family dynamics and provide appropriate support to the ambivalent donors.

Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model.

Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)-S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 105 ) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.

Navigating the COVID-19 pandemic: Initial impacts and responses of the Organ Procurement and Transplantation Network in the United States.

COVID-19 has been sweeping the globe, hitting the United States particularly hard with a state of emergency declared on March 13, 2020. Transplant hospitals have taken various precautions to protect patients from potential exposure. OPTN donor, candidate, and transplant data were analyzed from January 5, 2020 to September 5, 2020. The number of new waiting list registrations decreased, with the Northeast seeing over a 50% decrease from the week of 3/8 versus the week of 4/5. The national transplant system saw near cessation of living donor transplantation (-90%) from the week of 3/8 to the week of 4/5. Similarly, deceased donor kidney transplant volume dropped from 367 to 202 (-45%), and other organs saw similar decreases: lung (-70%), heart (-43%), and liver (-37%). Deceased donors recovered dropped from 260 to 163 (-45%) from 3/8 compared to 4/5, including a 67% decrease for lungs recovered. The magnitude of this decrease varied by geographic area, with the largest percent change (-67%) in the Northeast. Despite the pandemic, discard rates across organ has remained stable. Although the COVID-19 pandemic continues to evolve, OPTN data show recent evidence of stabilization, an indication that an early recovery of the number of living and deceased donors and transplants has ensued.

Randomized controlled trial of a quadratus lumborum block with liposomal bupivacaine for postoperative analgesia in laparoscopic donor nephrectomy.

Perioperative pain management is an important consideration in early recovery and patient satisfaction following laparoscopic donor nephrectomy. Transmuscular quadratus lumborum block has been described to reduce pain and opioid usage following several abdominal surgeries. In this prospective single-blind randomized controlled trial, we compared 52 patients who adhered to our institutional donor nephrectomy Early Recovery After Surgery pathway, which includes a laparoscopic-guided transversus abdominus plane block, to 40 patients who additionally received a transmuscular quadratus lumborum block with liposomal bupivacaine. Compared to control patients, those who received the block spent longer in the operating room prior to the surgical start (65.4 vs. 51.6 min, P < .001). Both groups had similar total hospital length of stay (33.3 h vs. 34.4 h, P = .61). Pain scores from postoperative days 0-30, number of patients requiring opioids, postoperative nausea, and pain management satisfaction were similar between both groups. Patients who received the block consumed less opioid on postoperative day 1 compared to controls (P = .006). No complications were attributable to the block. The quadratus lumborum block provides a safe pain management adjunct for some patients, and may reduce opioid use in the early postoperative period when combined with our standard institutional protocol for kidney donors.

A distance-based living donor kidney education program for Black wait-list candidates: A feasibility randomized trial.

Addressing racial disparities in living donor kidney transplants (LDKT) among Black patients warrants innovative programs to improve living donation rates. The Living Organ Video Educated Donors (LOVED) program is a 2-arm, culturally-tailored, distance-based, randomized controlled feasibility trial. The group-based, 8-week program used peer-navigator led video chat sessions and web-app video education for Black kidney waitlisted patients from United States southeastern state. Primary feasibility results for LOVED (n = 24) and usual care (n = 24) arms included LOVED program tolerability (i.e., 95.8% retention), program fidelity (i.e., 78.9% video education adherence and 72.1% video chat adherence). LDKT attitudinal and knowledge results favored the LOVED group where a statistically significant effect was reported over 6-months for willingness to approach strangers (estimate ± SE: -1.0 ± .55, F(1, 45.3) = 7.5, P = .009) and self-efficacy to advocate for a LDKT -.81 ± .31, F(1, 45.9) = 15.2, P < .001. Estimates were improved but not statistically significant for willingness to approach family and friends, LDKT knowledge and concerns for living donors (all P's > .088). Secondary measures at 6 months showed an increase in calls for LOVED compared to usual care (P = .008) though no differences were found for transplant center evaluations or LDKTs. Findings imply that LOVED increased screening calls and attitudes to approach potential donors but feasibility outcomes found program materials require modification to increase adherence.

The combination of a male donor's high muscle mass and quality is an independent protective factor for graft loss after living donor liver transplantation.

We evaluated the hypothesis that grafts from donors with high muscle mass and quality may have a better outcome after living-donor-liver-transplantation (LDLT) than those from usual donors. A total of 376 primary adult-to-adult LDLT cases were enrolled in this study. Donor skeletal muscle mass index (SMI) and intramuscular adipose tissue content (IMAC) were used as markers of muscle mass and quality. In male donor cases (n = 198), those with higher SMI and lower IMAC than age-adjusted values were defined as the "high muscularity donors" (n = 38) and the others were defined as the "control" (n = 160). The high muscularity donor showed better 1-year (97% vs 82%, P = .020) and overall graft survival rate (88% vs 67%, P = .024) than the control group after LDLT. Contrastingly, the influence of the muscularity was not observed in female donor cases. Multivariable analysis including donor age confirmed that a high muscularity donor was an independent protective factor for overall graft survival after LDLT (hazard ratio, 0.337; 95% CI: 0.101-0.838; P = .017). Our study first confirmed that high muscle mass and quality of a male donor is a protective factor of allograft loss after LDLT, independently from donor age.

Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins.

This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

The kidney evaluation of living kidney donor candidates: US practices in 2017.

We surveyed US transplant programs to assess practices used to assess kidney health in living kidney donor candidates in 2017; the response rate was 31%. In this report, we focus on the kidney; a companion piece focuses on the metabolic and cardiovascular aspects of candidate evaluation. Compared to 2005, programs have become more stringent in accepting younger candidates and less stringent in accepting older candidates. The 24-hour creatinine clearance remains the mainstay for kidney function assessment, with 74% continuing to use a value below 80 mL/min/1.73 m2 for exclusion and 22% using age-based criteria. ApoL1 genotyping is obtained routinely or selectively by 45%, half of which use the high-risk genotype as an absolute exclusion criterion. For history of symptomatic stones, 49% accept if there is no current radiographic evidence of stones and urine profile is low risk, 80%-95% consider candidates with unilateral asymptomatic stones, but only 33%-48% consider if stones are bilateral. In addition, 14% use the risk assessment tool developed by Grams et al routinely for decision-making, and 42% use it sometimes. Also, 57% reported not having yet determined a risk threshold for acceptable postdonation risk above which candidates are excluded. Contemporary practice variation underscores the need for better evidence to guide the donor selection process.

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors.

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow-up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs' NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.

Early graft losses in paired kidney exchange: Experience from 10 years of the National Kidney Registry.

Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There are sparse data on the rate of primary nonfunction (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (February 14, 2009 to December 31, 2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first-year posttransplant and assessed potential risk factors. Of 2364 transplants, there were 38 grafts (1.6%) lost within the first year, 13 (0.5%) with PNF. When compared to functioning grafts, there were no clinically significant differences in blood type compatibility, degree of HLA mismatch, number of veins/arteries, cold ischemia, and travel times. Of 13 PNF cases, 2 were due to early venous thrombosis, 2 to arterial thrombosis, and 2 to failure of desensitization and development of antibody-mediated rejection (AMR). Given the low rate of PNF, the NKR created a policy to allocate chain-end kidneys to recipients with PNF following event review and attributable to surgical issues of donor nephrectomy. It is expected that demonstration of low incidence of poor early graft outcomes and the presence of a "safety net" would further encourage program participation in national KPD.

Long-term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study.

This study aimed to evaluate postoperative long-term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.

The "oldest and coldest" shipped living donor kidneys transplanted through kidney paired donation.

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation ("oldest kidneys") and prolonged cold ischemia time ("coldest kidneys") on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death-censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.