Addition of a liver to the normothermic perfusion circuit reduces renal pro-inflammatory factors.

BACKGROUND: Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit. METHODS: Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30-min warm ischemia time and 90-min cold ischemia time. The liver-kidney NMP group (n = 5) and the single-kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared. RESULTS: The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver-kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver-kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL-6, IL-8, IL-1ß, NLRP3, and GSDMD. CONCLUSIONS: Our results indicated that the expression of renal pro-inflammatory factors was reduced in the liver-kidney NMP system.

Substantial decline of organ preservation fluid contamination following adoption of ischemia-free liver transplantation: a post-hoc analysis.

INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.

Metabolomics Differences of the Donor Livers Between In Situ and Ex Situ Conditions During Ischemia-free Liver Transplantation.

BACKGROUND: Ischemia-free liver transplantation (IFLT) has been innovated to avoid graft ischemia during organ procurement, preservation, and implantation. However, the metabolism activity of the donor livers between in the in situ and ex situ normothermic machine perfusion (NMP) conditions, and between standard criteria donor and extend criteria donor remains unknown. METHODS: During IFLT, plasma samples were collected both at the portal vein and hepatic vein of the donor livers in situ during procurement and ex situ during NMP. An ultra-high performance liquid chromatography-mass spectrometry was conducted to investigate the common and distinct intraliver metabolite exchange. RESULTS: Profound cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis were found in both in situ and ex situ conditions. However, obvious D-arginine and D-ornithine metabolism, arginine and proline metabolism were only found in the in situ condition. The suppressed activities of the urea cycle pathway during ex situ condition were confirmed in an RNA expression level. In addition, compared with extend criteria donor group, standard criteria donor group had more active intraliver metabolite exchange in metabonomics level. Furthermore, we found that the relative concentration of p-cresol, allocystathionine, L-prolyl-L-proline in the ex situ group was strongly correlated with peak alanine aminotransferase and aspartate aminotransferase at postoperative days 1-7. CONCLUSIONS: In the current study, we show the common and distinct metabolism activities during IFLT. These findings might provide insights on how to modify the design of NMP device, improve the perfusate components, and redefine the criteria of graft viability.

The Microstructural Evolution and Grain Growth Kinetics of Fine-Grained Extruded Mg-Nd-Zn-Zr Alloy.

The microstructure evolution and grain growth kinetics of the fine-grained extruded Mg-Nd-Zn-Zr alloy were investigated by holding the extruded plate for a wide range of time in the temperature range of 470 °C to 530 °C. By observing the optical micrographs, it was found that the material showed abnormal grain growth at the experimental condition of 470 °C × 24 h, and the time point of abnormal grain growth appeared significantly earlier with the increase in the experimental temperature. The evaluation of the second phase content within the alloy indicates that the presence of the second phase contributes to the microstructural stability of the Mg-Nd-Zn-Zr alloy. However, the slow coarsening/dissolution of the second phase is an important cause of abnormal grain growth. Based on the experimental data, the isothermal grain growth kinetic models of the fine-grained extruded Mg-Nd-Zn-Zr alloy were developed based on the Sellars model. The grain growth exponent was in the range of 5.5-8 and decreased gradually with the increase in the experimental temperature. The grain growth activation energy is approximately 150.00 kJ/mol, which is close to the bulk diffusion activation energy of magnesium, indicating that the grain growth is controlled by lattice diffusion. By energy spectrometry (EDS), the compositional changes of the second phase within this alloy at 500 °C were investigated.

Prediction of Graft Survival Post-liver Transplantation by L-GrAFT Risk Score Model, EASE Score, MEAF Scoring, and EAD.

Background: Early allograft dysfunction (EAD) is correlated with poor patient or graft survival in liver transplantation. However, the power of distinct definitions of EAD in prediction of graft survival is unclear. Methods: This retrospective, single-center study reviewed data of 677 recipients undergoing orthotopic liver transplant between July 2015 and June 2020. The following EAD definitions were compared: liver graft assessment following transplantation (L-GrAFT) risk score model, early allograft failure simplified estimation score (EASE), model for early allograft function (MEAF) scoring, and Olthoff criteria. Risk factors for L-GrAFT7 high risk group were evaluated with univariate and multivariable logistic regression analysis. Results: L-GrAFT7 had a satisfied C-statistic of 0.87 in predicting a 3-month graft survival which significantly outperformed MEAF (C-statistic = 0.78, P = 0.01) and EAD (C-statistic = 0.75, P < 0.001), respectively. L-GrAFT10, EASE was similar to L-GrAFT7, and they had no statistical significance in predicting survival. Laboratory model for end-stage liver disease score and cold ischemia time are risk factors of L-GrAFT7 high-risk group. Conclusion: L-GrAFT7 risk score is capable for better predicting the 3-month graft survival than the MEAF and EAD in a Chinese cohort, which might standardize assessment of early graft function and serve as a surrogate endpoint in clinical trial.

Clinical Outcomes of Liver Transplantation in Patients With Hepatorenal Syndrome: A Single Center Study in China.

BACKGROUND: Liver transplantation (LT) is an optimal treatment for hepatorenal syndrome (HRS) patients but renal function recovery is not universal after operation. The aim of this study is to explore the association between stages of hepatorenal syndrome-acute kidney injury (HRS-AKI) and incidence of post-operation chronic kidney disease (CKD). METHODS: Data of HRS-AKI patients who received LT were collected from the First Affiliated Hospital of Sun Yat-sen University from 2016 to 2020. A survival and incidence curve and multivariable model were established to analyze the impacts of HRS-AKI stages and variables on 90-day survival and CKD within 12 months. RESULTS: A total of 62 HRS-AKI patients were enrolled in this study. Overall, 35 (57%), 17 (27%), and 10 (16%) patients were diagnosed as stages 1, 2, and 3, respectively. The patients at stage 3 had the poorest outcomes with the lowest rate of 90-day survival and the highest incidence of CKD in 12 months. Stage 3 (SHR = 7.186, 95% CI, 1.661-32.043) and postoperative renal replacement therapy (RRT) (SHR = 3.228, 95% CI, 1.115-9.345) were found as useful indicators for poor prognosis. CONCLUSIONS: In our study, the classification of HRS-AKI stages can be used to predict the prognosis of HRS patients after LT. The peak serum creatinine level is a risky predictor in high HRS-AKI stage patients.