Mathur, Amit

ABSTRACT Despite the annual increase in liver transplants, a persistent disparity between suitable donors and recipients continues to challenge the transplant community. The introduction of machine perfusion emerged as a novel approach to organ preservation. This technique, which utilizes extended criteria donor grafts, is expected to reduce rejection rates and expand the donor pool. Its principle, like that of any ex vivo machine perfusion, is based on the continuous supply of nutrients and oxygen to maintain cellular metabolism while interrupting anaerobic processes. This helps prevent conditions such as ischemia-reperfusion injury, early graft dysfunction, and ischemic cholangiopathy, which can lead to graft loss and the need for retransplantation. There are two main modes of ex vivo machine perfusion: hypothermic and normothermic, differentiated by the operating temperature. Utilizing ex situ perfusion machines presents a promising opportunity to increase liver graft usage and reduce waitlist times. However, it is crucial to evaluate how much this technology would raise the overall cost of transplants. In Brazil, implementing a machine perfusion program may encounter unique challenges not seen in other countries. These challenges include limited access to the healthcare system for high-risk liver transplant candidates, long waiting lists, inadequate support for organ donors, reliance solely on deceased brain-dead donors, since donation after cardiac death is not ethically accepted, and geographical barriers.

Key Points Health care utilization rates in elderly kidney transplant were no different between the high kidney donor profile index and low kidney donor profile index group. Number of readmissions and surgical interventions in elderly kidney transplant was no different between the high kidney donor profile index and low kidney donor profile index group. Death censored graft loss was higher in the high kidney donor profile index group, whereas the patient survival was no different between the high kidney donor profile index and low kidney donor profile index groups. Background High kidney donor profile index (KDPI) kidneys (KDPI >85%) are often associated with increased risks of post-kidney transplant (KT) complications and greater health care utilization (HCU), particularly in elderly recipients with multiple comorbidities. These concerns frequently lead to underutilization of high KDPI kidneys in older transplant candidates, thereby limiting their access to transplantation despite potential clinical benefits. The aim of this study was to compare post-KT HCU between elderly recipients of high versus low KDPI deceased donor kidneys. The primary outcome included differences in hospital readmissions, surgical interventions, and outpatient service use at multiple post-transplant time points. Secondary outcome included graft function, graft survival, and patient survival. Methods A retrospective analysis of elderly solitary KT recipients (age ≥65 years) between January 1, 2011, and December 31, 2020. Patients were stratified into high KDPI (>85%, n =160) and low KDPI (≤85%, n =453) groups. We assessed inpatient and outpatient HCU, including readmissions at 30, 90, and 365 days post-transplant, surgical interventions, and outpatient visits (emergency department, transplant clinic, endocrine clinic, and ambulatory infusion units). Results There were no statistically significant differences between high and low KDPI groups in rates of hospital readmissions, surgical interventions, or outpatient visits (all P > 0.05). Delayed graft function rates were also similar ( P = 0.61). The low KDPI group had significantly higher eGFR at 4 months, 1, 2, and 3 years post-transplant (all P < 0.001). However, days alive and out of the hospital within 90 and 365 days post-transplant were comparable between the groups (all P > 0.05). Overall patient survival was similar ( P = 0.08), although death-censored graft loss was significantly higher in the high KDPI group ( P = 0.001). Conclusions Among elderly KT recipients, high KDPI kidney recipients had comparable post-transplant HCU and overall survival with those receiving low KDPI kidneys, despite lower long-term graft function. These findings suggest that high KDPI kidneys remain a viable option for older patients, offering timely access to transplantation.

ABSTRACT Introduction Donation after circulatory death (DCD) allografts are underutilized in liver transplantation (LT) due to increased risk of complications. These risks stem from ischemic injury sustained during the total donor warm ischemia time (tDWIT), historically limited to 30 min. Normothermic machine perfusion (NMP) can mitigate these risks and facilitate LT of DCD grafts with extended tDWIT. We aimed to compare outcomes of DCD allografts with extended tDWIT preserved on NMP versus static cold storage (SCS). Methods This single‐center study included adult DCD LT with tDWIT ≥ 30 from 2019 to 2023. Outcomes of NMP and SCS were compared including EAD, IC, graft survival, and patient survival. Results Among 68 DCD LT with tDWIT ≥ 30, 64.7% ( n = 44) were preserved with NMP and 35.3% ( n = 24) with SCS. No differences in donor or recipient demographics were observed. The median tDWIT was 33 min for NMP and 30.5 min for SCS ( p < 0.01). Despite longer tDWIT, the NMP group had lower rates of EAD (4.5% vs. 66.7%, p < 0.01) and IC (2.3% vs. 29.2%, p < 0.01). One‐year graft survival was higher in NMP ( p < 0.01), and 1‐year patient survival was comparable between groups ( p = 0.18). Conclusion NMP challenges traditional tDWIT constraints and can increase the pool of viable DCD allografts for transplantation.

ABSTRACTThis single‐center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post‐transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24–24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

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.

Ex-situ machine perfusion of the liver has surmounted traditional limitations associated with static cold storage in the context of organ preservation. This innovative technology has changed the landscape of liver transplantation by mitigating ischemia perfusion injury, offering a platform for continuous assessment of organ quality, and providing an avenue for optimizing the use of traditionally marginal allografts. This review summarizes the contemporary clinical applications of machine perfusion devices and discusses potential future strategies for real-time viability assessment, therapeutic interventions, and modulation of organ function after recovery.

ABSTRACTIntroductionThe 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.MethodsData 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.ResultsAmong 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.ConclusionsFinancial 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.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

AbstractIntroductionExpedited out‐of‐sequence deceased donor kidney allocation is a strategy to avoid discards after early placement attempts have been unsuccessful. Our study aimed to assess outcomes and characteristics of these transplanted kidneys.MethodsKDPI matching was performed between expedited allocation (EA) and standard allocation (SA) deceased donor kidney transplants performed at our center.ResultsBetween 2018 and 2021, there were 225 EA offers, and 189 (84%) were transplanted. EA recipients were older (p = .007) and had shorter dialysis vintage (p < .0001). EA kidneys were likely to be nationally allocated (p < .001), have AKI (p < .0001) and longer CIT (p < .0001). There were no differences in EA and SA time‐zero kidney biopsies (ci, p = .07; ct, p = .89; cv, p = .95; ah, p = .79). EA kidneys had more DGF (p = .0006), but there were no differences in DGF duration (p = .83), hospital length of stay (p = .43), 1‐ and 2‐year eGFR (p = .16, p = .99), patient (p = .34), or death‐censored graft (p = .66) survival.ConclusionDuring this study period, our center transplanted 189 kidneys through EA following local‐regional declines. These kidneys often came from AKI donors and had more DGF but had similar outcomes to KDPI‐matched SA kidneys. Although it has been suggested that EA has the potential to worsen transplant disparities, transplant center level decisions on organ acceptance contribute to these variations.

Introduction Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. Project aim The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. Design This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Results Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P = .001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P = .001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P = .001). Early allograft dysfunction was common (54.1% vs 52.5%, P = .75) and did not impact hospital length of stay (median 5 vs 6 days, P = .89). There were no differences in biliary complications ( P = .11). There were no differences in patient ( P = .88) or graft survival ( P = .35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Conclusion Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts.