Preservation of Discarded Human Kidneys for 10 days at Subzero Temperature

American Journal of Transplantation · 2025-01-01

Optimizing DCD donor liver function with resveratrol during machine perfusion

Scientific Reports · 2025-11-26 · 1 citations

Extensive research has explored the use of machine perfusion to repair liver grafts, among these, interventions targeting mitochondrial repair are gaining attention due to its central role in ischemia-reperfusion injury and graft viability. Resveratrol, a mild natural polyphenol, is investigated here as a representative compound. Rat donor livers were subjected to 30 min of asystolic warm ischemia (DCD), followed by 2 h of either static cold storage (SCS), subnormothermic machine perfusion (SNMP) at 25 °C, or SNMP supplemented with resveratrol (SNMP-RES). All livers were subsequently reperfused under normothermic conditions for 1 h (NMP) with donor blood. Biochemical, transcriptomics RNA sequencing, inflammatory, and histological analyses were performed on perfusate samples and liver tissue biopsies. Resveratrol significantly enhanced the protective effects of SNMP, reducing perfusate AST (p = 0.03) and flavin mononucleotide (FMN) (p = 0.01). Resveratrol also decreased perfusate cytokine levels and improved tissue morphology. Transcriptomic analysis identified an upregulation of regenerative pathways using resveratrol, including Notch-signaling and Wnt signaling. The innate immune response was downregulated. This study represents the potential of FMN as a marker for liver quality during SNMP for the first time and demonstrates resveratrol's effects during SNMP. These findings encourage further exploration of mitochondrial-targeted preservation strategies and validate long-term benefits.

Rapamycin Treatment During Normothermic Machine Perfusion of Discarded Human Livers Supports Level of Graft Function Required for Transplantation

American Journal of Transplantation · 2025-01-01

UW supplementation with AP39 improves liver viability following static cold storage

Scientific Reports · 2025-01-09 · 5 citations

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H2S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H2S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H2S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.

Association of Kidney Graft Long-term Outcome With Recipient Cystathionine Gamma-lyase Polymorphisms and Hydrogen Sulfide Levels: A Cohort Study

Transplantation Direct · 2025-04-17

Background. Hydrogen sulfide (H 2 S) produced endogenously by the CTH gene-encoded cystathionine gamma-lyase protects from renal ischemia–reperfusion injury in preclinical models. Here, we hypothesized that CTH gene polymorphisms (single nucleotide polymorphism [SNP]) and recipient H 2 S serum levels influence kidney graft outcomes after transplantation. Methods. We included all consecutive recipients of a first kidney transplant in the Swiss Transplant Cohort Study and with available genotyping. In addition, 192 deceased-donor kidney transplant recipients were randomly selected to measure baseline serum H 2 S levels. The primary endpoint was graft loss during follow-up. Results. CTH SNPs were identified in up to 50% of the patients. During median follow-up (6.4 y, interquartile range: 3.9–9.8), graft loss was observed in 247 (9.8%) of 2518 patients. The incidence of graft loss was associated with the presence or absence of CTH SNPs. Specifically, rs672203 and rs10458561, increased the risk of graft loss (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = 0.02; and HR: 1.29, 95% CI: 1.0-1.66, P = 0.05; respectively), whereas rs113285275 was protective (HR: 0.78, 95% CI: 0.6-1.01, P = 0.05). Interestingly, rs672203 was associated with an increased risk of acute rejection ( P = 0.05), whereas rs113285275 was associated with a lower risk of acute rejection ( P = 0.01). Finally, in patients with delayed graft function, serum H 2 S levels correlated with lower graft dysfunction (defined as estimated glomerular filtration rate <30 mL/min/1.73 m 2 ) ( P = 0.05). Conclusions. Graft outcome after kidney transplantation was associated with CTH genotype and, to some extent, H 2 S serum levels. Further research is needed to define the underlying protective mechanisms.

Su1650: EVALUATING THE IMPACT OF A MULTI-DISCIPLINARY CLINIC TO PREVENT ALCOHOL RELAPSE IN HIGH-RISK PATIENTS AFTER LIVER TRANSPLANT FOR ALCOHOL-RELATED LIVER DISEASE

Gastroenterology · 2025-05-01

Preventing Alcohol Relapse in High-Risk Liver Transplant Recipients: Evaluation of a Multi-Disciplinary Post-Transplant Clinic

American Journal of Transplantation · 2025-08-01

Effect of Hepatic Arterial Reconstruction prior to On-Site Normothermic Machine Perfusion in Donation after Circulatory Death Liver Transplant.

Experimental and Clinical Transplantation · 2025-08-01

OBJECTIVES: On-site normothermic machine perfusion of the liver may require hepatic arterial reconstruction. The effect of arterial reconstruction on the deve-lopment of primary ischemic cholangiopathy has not been fully elucidated in liver transplants with organs donated after circulatory death. The aim of this study was to evaluate the effect of normothermic machine perfusion with arterial reconstruction at the onset of ischemic cholangiopathy in liver transplants with organs donated after circulatory death. MATERIALS AND METHODS: We retrospectively reviewed 93 patients who had received liver transplants donated after circulatory death for the period from 2015 to 2023 at a single institution. The primary endpoint was the onset of primary ischemic cholangiopathy within 1 year after donation after circulatory death liver transplant, excluding secondary ischemic cholangiopathy due to arterial complications. RESULTS: Normothermic machine perfusion was used for 71 cases, whereas standard cold storage was applied for 22 cases. Arterial reconstruction was performed in 14.1% of cases versus 27.3% of cases without normothermic machine perfusion. The cumulative onset of ischemic cholangiopathy was 7.0% versus 27.2% without normothermic machine perfusion (P = .013). In the group with normothermic machine perfusion, competing risk analyses demonstrated that the cumulative ischemic cholangiopathy onset rate was significantly higher in the group with arterial reconstruction (30.0%) versus without arterial reconstruction (3.3%) (P < .003). Total cold ischemia time and cold ischemia time between liver recovery and normothermic machine perfusion initiation were significantly longer in the group with arterial reconstruction (P < .001), without significant differences in arterial flow on normothermic machine perfusion and other relevant factors. CONCLUSIONS: In donation after circulatory death liver transplant recipients with normothermic machine perfusion, arterial reconstruction is a risk factor for developing ischemic cholangiopathy, likely mediated by cold ischemia time prolongation.

Dietary or Pharmacological inhibition of Insulin-Like Growth Factor-1 Protects from Renal Ischemia-Reperfusion Injury

American Journal of Transplantation · 2025-01-01

Liver Transplant Provider Perspectives on Posttransplant Management of Alcohol Use Disorder

Transplantation Direct · 2025-03-10 · 1 citations

Background: Liver transplantation (LT) is the standard treatment for liver failure secondary to alcohol-associated liver disease, but limited literature and best practices exist for post-LT treatment of alcohol use disorder (AUD). This study explores current AUD management practices and providers' perceived barriers to effective post-LT AUD management. Methods: A 45-item survey on post-LT AUD treatment practices was distributed to members of the American Society of Transplant Surgeons, the Association of Consult/Liaison Psychiatry Transplant Special Interest Group, and both the American Society of Transplantation's Liver and Intestine Community of Practice and Psychosocial and Ethics Community of Practice discussion boards, between December 2021 and April 2022. Univariate analysis of categorical variables was performed using the chi-square test. Data were analyzed using center volume tertiles, country region, and provider professional activity. Results: Two hundred thirty-two respondents from 70 LT centers across all 11 United Network for Organ Sharing regions completed the survey. Half of the them were attending physicians and 16.4% were nurse coordinators. Most centers (84%) aimed for alcohol abstinence for all post-LT patients. Perceived barriers to AUD treatment efficacy included ongoing desire to drink (18%), denial about alcohol misuse (14.9%), and lack of posttransplant support (14%). Additionally, 62.1% of centers had no policy for prescribing medication-assisted therapy to treat AUD, and 32.7% of centers reported no center-level changes in AUD care. Providers identified primary needs as hiring additional mental health professionals (30.8%), dedicating specific staff to AUD care (24.7%), and standardizing psychiatric/psychological care in transplant clinics (17.2%). Conclusions: Despite the increasing volume of LT for alcohol-associated liver disease, significant perceived barriers to effective AUD treatment remain.