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.

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.

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.

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.

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.

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.

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.

Living versus deceased kidney transplantation: Comparison of complications.

INTRODUCTION: It is assumed that the outcome of kidney transplantation from living donors is more favorable than deceased donors. However, over the years there has been an overall improvement in transplant survival from both living and deceased donors. In this article we have evaluated and compared the most recent results in living and deceased donor kidney transplantations. PATIENTS AND METHODS: Four hundred and forty six patients underwent kidney transplantation in our center from September 2009 to March 2014. The patients divided in two groups living (group A) and deceased (group B) donor transplantation groups. The patients were followed until September 2016. Acute rejection, graft survival, delayed graft function, renal artery thrombosis, graft nephrectomy, ureterocutaneous fistula, postoperative hypertension, mortality, hospital stay, hyperlipidemia, post transplantation diabetes and lymphocele rate measured and compared in two groups. RESULTS: Most variables were not different between the two groups except lymphocele and delayed graft function. Lymphocele was more prevalent in group A (13.8% vs 3.1%, p-value = 0.02) and delayed graft function results were more desirable in living donor transplantation group (group B). CONCLUSION: Although, delayed graft function was less common in transplantation from living donors, short, and long term graft survival was not significantly different in this study.

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.