Robert J Porte’s research while affiliated with Erasmus MC and other places

Background & Aims: Normothermic machine perfusion (NMP) is used to preserve and assess the viability of (extended criteria) high-risk donor livers. Long-term NMP (LT-NMP; ≥24h) is emerging as a method to improve or repair livers initially deemed unsuitable for transplantation. This study investigated metabolism during LT-NMP, focusing on hepatic energy consumption and nitrogen and electrolyte balances to better understand long-term perfusion requirements. Methods: In this study, we measured oxygen consumption (V̇ CO2) and carbon dioxide production (V̇ O 2 ) to determine the energy expenditure of 14 human livers during LT NMP for 7 days. Additionally, hepatic balances of glucose and lactate, as well as of nitrogen and electrolytes were determined. Results: Initial high metabolic rates during the first day of LT-NMP decreased and stabilized at nearly 50% on day 3, suggesting a quiescent state until day 7. Most energy was derived from glucose (75-88%). Continuous amino acid supplementation was essential to maintain an anabolic state, whereas livers without supplementation became catabolic. While net electrolyte balances were close to zero, significant uptake and release of electrolytes occurred throughout LT-NMP. Conclusions: During LT-NMP, livers reached a metabolically quiescent state after 3 days with decreased energy consumption. Tailoring perfusate composition and supplementation protocols to the specific needs of the liver could enhance organ preservation and potentially expand the pool of viable donor livers after LT-NMP.

Background Normothermic machine perfusion (NMP) enables pretransplantation assessment of donor liver viability to increase donor liver utilization. However, unambiguous objective criteria to determine integrated liver function during NMP to decide upon acceptance are still lacking. This study investigates whether the indocyanine green (ICG) elimination test can be applied to assess liver function during NMP. Methods Donor livers underwent dual-hypothermic oxygenated machine perfusion and NMP. The ICG elimination test was improved during an optimization phase (n = 10) and tested against current functional perfusion parameters and posttransplantation outcomes in clinically perfused livers (n = 32). Results The ICG plasma disappearance rate (PDR) during NMP was dependent on perfusion blood flow and liver weight. The corrected PDR (NMP-PDR) was correlated to the hepatic extraction rate ( R = 0.923; P > 0.001) and ATP content in liver biopsies at 2 h of NMP ( R = 0.692; P = 0.027). In the clinical phase, the length of the functional warm ischemia time in the donation process was inversely correlated to the NMP-PDR ( P = 0.042). Both individual acceptance criteria (lactate clearance, ability of self-regulate pH, Δbicarbonate, and ΔpH) and overall hepatocellular and cholangiocellular acceptance criteria were correlated to the NMP-PDR. The NMP-PDR was higher in the cohort accepted for transplantation (n = 18; 18.1%/L·kg [14.0% to 22.7%/L·kg]) than in the nontransplanted cohort (n = 14; 11.8%/L·kg [8.8% to 12.9%/L·kg]; P < 0.0001). Furthermore, the NMP-PDR correlated with the liver graft assessment following transplantation at 7 d score posttransplantation ( R = –0.551; P = 0.027). Conclusions We demonstrate that the NMP-PDR correlates with both liver function during NMP and short-term posttransplantation outcomes. This simple objective test has the potential to increase donor liver utilization rate, while preventing hepatocellular dysfunction posttransplantation.

Background Both hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) are increasingly used for preservation of deceased donor kidneys. However, especially NMP can pose as a risk for microbial contamination of the kidney graft as the 37°C perfusate can act as a breeding ground for microbial contaminants. Methods In this study, we investigated the cultures of HMP and NMP perfusates of deceased donor kidneys. Results Between January 2021 and April 2024, a total of 99 perfusates were examined (73 HMP and 26 NMP perfusates)‐. We found that contamination of HMP perfusate was common, occurring in 21 of 73 cultures (29%). Most bacteria originated from the skin. Microbial contamination during NMP was rare, occurring only in 2 of 26 cultures (8%). Microbial contamination during machine perfusion did not lead to infectious complications in the recipients. Conclusion Machine perfusion poses a very limited risk of infection in kidney transplant recipients. image

The shortage of suitable donor organs has resulted in the use of suboptimal, high-risk, extended-criteria donor (ECD) livers, which are at an increased risk of failure after transplantation. Compared with traditional static cold storage, dynamic preservation by ex situ machine perfusion reduces the risks associated with the transplantation of ECD organs. Ex situ machine perfusion strategies differ in timing (that is, speed of procurement and transport), perfusion duration and perfusion temperature. For 'back-to-base' protocols, the donor liver is statically cold stored during transportation to the recipient hospital (the 'base') and then perfused, instead of transporting the liver using a portable perfusion system. While dual hypothermic (8-12 °C) oxygenated machine perfusion (DHOPE) allows safe prolongation of preservation duration and reduces ischemia-reperfusion injury-related complications, including post-transplant cholangiopathy, normothermic machine perfusion (NMP) at 35-37 °C facilitates ex situ viability testing of both liver parenchyma and bile ducts. Here, we describe a clinical protocol for 'back-to-base' combined DHOPE and NMP, linked by a period of controlled oxygenated rewarming (COR), which we call the DHOPE-COR-NMP protocol. This protocol enables restoration of mitochondrial function after static ischemic preservation and minimizes both ischemia-reperfusion and temperature-shift-induced injury during the start of NMP. The NMP phase allows viability assessment before final donor liver acceptance for transplantation. Sequential DHOPE and COR-NMP may reduce the risks associated with transplantation of ECD livers and facilitate enhanced utilization, thereby helping to alleviate the organ shortage.

Background The global shortage of suitable donor livers for transplantation has prompted efforts to expand the donor pool by using extended criteria donors. Machine preservation technology has shown promise in optimizing graft preservation and improving logistics. Additionally, it holds potential for organ repair, regeneration, therapeutic applications during extended preservation periods, and enhancing organ allocation. Methods We conducted a comprehensive literature review using PubMed, Embase, and Web of Science databases. All studies published between January 1, 2022, and February 7, 2024, that described machine perfusion preservation of livers for more than 24 h were eligible for inclusion. The findings were synthesized in a narrative review format to highlight key benefits and advancements. Results We identified eleven studies from multiple research groups, employing various techniques, devices, and preservation durations. Perfusion durations ranged from 1 to 13 days, with notable variations in protocols for long‐term preservation beyond 24 h. Viability was assessed during perfusion only. No livers were transplanted. Among the reviewed studies, the introduction of a dialysis system emerged as the most effective strategy for managing waste accumulation during long‐term liver perfusion. Differences were also observed in hemodynamics, oxygenation, organ chambers, supplemental regimens, and glycemic control. Conclusion Over the past two years, substantial progress has been made in refining protocols for long‐term liver machine perfusion, with significant advancements in waste management, enabling successful multi‐day perfusions. While these developments are promising, further research is necessary to standardize and optimize long‐term perfusion protocols, establishing a reliable platform for both organ preservation and therapeutic applications.

Background KEPs (kidney exchange programs) facilitate living donor kidney transplantations (LDKT) for patients with incompatible donors, who are typically higher risk than non-KEP patients because of higher sensitization and longer dialysis vintage. We conducted a comparative analysis of graft outcomes and risk factors for both KEP and non-KEP living donor kidney transplants. Methods All LDKTs performed in the Netherlands between 2004-2021 were included. The primary outcome measures were one-, five- and 10-year death censored graft survival (DCGS). The secondary outcome measures were delayed graft function (DGF), graft function, rejection rates and patient survival. We used a propensity score matching model to account for differences at baseline. Results Out of 7536 LDKTs, 694 (9%) were transplanted via the KEP. Ten-year graft survival was similar for KEP 0.916 (95% CI: 0.894 - 0.939) and non-KEP 0.919 (0.912 - 0.926, p = 0.82). We observed significant differences in five-year rejection (12% vs 7%), and five-year patient survival (KEP: 84%, non-KEP: 90%), which was non-significant after propensity score matching. Significant risk factors for lower graft survival included high donor age, re-transplantations, extended dialysis vintage, higher panel reactive antibodies, and nephrotic syndrome as the cause of end-stage kidney disease . Conclusions Transplantation via KEP offers a viable alternative for patients lacking compatible donors, avoiding specific and invasive pre- and post-transplant treatments. KEP's similar survival rate to non-KEP suggests prioritizing KEP LDKT over deceased donor kidney transplantation, desensitization, and dialysis. However, clinicians should consider the identified risk factors when planning and managing pre- and post-transplant care to enhance patient outcomes. Thus, we advocate for the broad adoption of KEP and establishment in regions lacking such programs, alongside initiation and expansion of international collaborations.

Background Normothermic machine perfusion (NMP) is increasingly used to preserve and assess donor livers prior to transplantation. Due to its success, it is expected that more centers will start using this technology. However, NMP may also cause adverse effects. Methods In this retrospective, observational study, we investigated the effect of NMP pressures on donor liver weight, post‐transplant outcomes, and hepatic perfusion characteristics. A total of 36 livers were transplanted after NMP. NMP perfusion pressure settings were lowered from a median (IQR) of 47 mmHg (42–54) to 34 mmHg (30–39) for the hepatic artery (HA), and from 8 mmHg (7–10) to 7 mmHg (6–8) for the portal vein (PV) to diminish potential edema formation inside the liver. Results This change appeared to lead to a reduction of liver weight after NMP (−22 g to −143 g, p = 0.02), without affecting the PV flow velocity (35.5 to 48.0 cm/s, p = 0.54), or hepatocellular injury markers during NMP (AST 1511–1148 U/L, p = 0.44; ALT 318–849 U/L, p = 0.35), and post‐transplantation outcomes. Changes in liver weight correlated significantly with the applied PV pressure during NMP ( r = 0.52, p < 0.01) and the HA flow ( r = 0.38, p < 0.05). Conclusion NMP can lead to a reduction in liver weight, which might be masked by edema when high perfusion pressures are used. We encourage applying the lowest perfusion pressures possible to reach adequate flows and oxygen supply during liver NMP.