A Proof of Concept Study on Real-Pime LiMAx CYP1A2 Liver Function Assessment of Donor Grafts During Normothermic Machine Perfusion

No single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts

The Impact of Combined Warm Ischemia Time on Development of Acute Kidney Injury in Donation after Circulatory Death Liver Transplantation: Stay Within the Golden Hour

Background Acute kidney injury (AKI) is a common complication after liver transplantation and more frequently observed when high-risk grafts, such as donation after circulatory death (DCD) grafts are used. Our aim was to investigate the impact of the ischemia periods on development of AKI in DCD liver transplantation. Methods We performed a 2-center retrospective study with 368 DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac arrest-start cold perfusion). We introduced a new period of warm ischemia: the combined warm ischemia time (combined WIT), which was defined as the sum of DWIT and recipient WIT. Results AKI was observed in 65% of the recipients and severe AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in recipients with the most severe form of AKI (P &lt; 0.001). On multivariable analysis, increasing duration of the combined WIT was associated with an increased risk of developing severe AKI (odds ratio, 1.032 per every extra minute; 95% confidence interval, 1.014-1.051; P &lt; 0.001). No relation was observed between length of cold ischemia time and severe AKI. Conclusions Combined WIT is a newly defined period of warm ischemia in DCD liver transplantation. Length of combined WIT is associated with severity of postoperative AKI and should ideally not exceed 60 minutes

The Impact of Combined Warm Ischemia Time on Development of Acute Kidney Injury in Donation after Circulatory Death Liver Transplantation: Stay Within the Golden Hour

Background Acute kidney injury (AKI) is a common complication after liver transplantation and more frequently observed when high-risk grafts, such as donation after circulatory death (DCD) grafts are used. Our aim was to investigate the impact of the ischemia periods on development of AKI in DCD liver transplantation. Methods We performed a 2-center retrospective study with 368 DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac arrest-start cold perfusion). We introduced a new period of warm ischemia: the combined warm ischemia time (combined WIT), which was defined as the sum of DWIT and recipient WIT. Results AKI was observed in 65% of the recipients and severe AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in recipients with the most severe form of AKI (P &lt; 0.001). On multivariable analysis, increasing duration of the combined WIT was associated with an increased risk of developing severe AKI (odds ratio, 1.032 per every extra minute; 95% confidence interval, 1.014-1.051; P &lt; 0.001). No relation was observed between length of cold ischemia time and severe AKI. Conclusions Combined WIT is a newly defined period of warm ischemia in DCD liver transplantation. Length of combined WIT is associated with severity of postoperative AKI and should ideally not exceed 60 minutes