Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts Outcome of Liver Transplantation From Donation After Cardiac Death

Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis. This study aims to explore the relationship between pretransplant intrahepatic proteins and the incidence of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. Liver biopsy specimens of 105 pretransplant grafts used for LT were collected and used for immunohistochemistry analysis of 5 proteins. And matched clinical data of donor, recipient, transplantation, and prognosis were analyzed. The incidence of EAD was 41.9% (44/105) in this cohort. Macrovesicular steatosis (P = 0.016), donor body mass index (P = 0.013), recipients' pretransplant serum creatinine (P = 0.036), and intrahepatic expression of heme oxygenase 1 (HO1) (P = 0.015) and tumor necrosis factor α (TNF-α) (P = 0.039) were independent predictors of EAD. Inferior graft and recipient prognosis were observed in patients who experienced EAD (P = 0.028 and 0.031) or received grafts with higher expression of sirtuin 1 (P = 0.005 and 0.013). The graft and recipient survival were worst in patients with both EAD and high expression of sirtuin 1 (P = 0.001 and 0.004). In conclusion, pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated proteins showed superiority in distinguishing recipients with worse prognosis.

Abstract 11974: Impact of Routine ECPR Service on Availability of Donor Organs

Introduction: In refractory cardiac arrest, extracorporeal cardiopulmonary resuscitation (ECPR) may increase the chance of survival. However, in brain death or donation after cardiac death scenario, ECPR may also become an important organ donor source. Hypothesis: We hypothesized that 1/ the implementation of ECPR into the daily routine of a high volume cardiac arrest centre might increase the availability of organ donors, and 2/ ECPR might assure the same long-term function of donated organs as non-ECPR care. Methods: We retrospectively evaluated pre-ECPR (2007-2011) and ECPR (2012-2020) periods in terms of donors recruited from the out-of-hospital and in-hospital cardiac arrest population. We assessed the number of donors referred, the number of organs harvested and their one- and five-year survival. Results: In the pre-ECPR period, 11 donors were referred, of which 7 were accepted. During the ECPR period, the number of donors increased to 80, of which 42 were accepted. The number of donated organs in respective periods were 18 and 119, corresponding to 3,6 vs 13,2 (p =0.033) organs per year harvested. One-year survival of transplanted organs was 94.4% vs 100%, and five-year survival was 94.4% vs 87,5%, in relevant periods. Survival of organs obtained from donors after CPR and ECPR at one year (98.9% vs 100%) and five years (90,2% vs 88.9%) was the same. Graft failure was not the cause of death in any single case. Conclusions: Establishing a high volume cardiac arrest/ECPR centre may lead to a higher number of potential and subsequently accepted organ donors. The length of survival of donated organs is high and comparable between ECPR vs non-ECPR cardiac arrest donors.

Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System

Cardiac transplantation is the gold standard for treatment for select patients with end-stage heart failure, yet donor supply is limited. Ex vivo machine perfusion is an emerging technology capable of safely preserving organs and expanding the viable donor pool. The TransMedics® Organ Care System™ is an investigational device which mimics physiologic conditions while maintaining the heart in a warm, beating state rather than cold storage. The use of Organ Care System allows increased opportunities for using organs from marginal donors, distant procurement sites, donation after cardiac death, and in recipients with complex anatomy. In the future, bioengineering technologies including use of mesenchymal stem cells, viral vector delivery of gene therapy, and alternate devices may further broaden the field of ex vivo machine perfusion.

Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3–6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.

Donor type and 3-month hospital readmission following kidney transplantation: results from the Netherlands organ transplant registry

Background Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs. Methods We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders. Results Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly. Conclusion A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.