Comparing early liver graft function from heart beating and living‐donors: A pilot study aiming to identify new biomarkers of liver injury

Abstract

The liver and kidney functions of recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemia times were examined during the neohepatic phase for the elimination of rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods. Metabolomics and the relative expressions of miR-122, miR-148a and γ-glutamyltranspeptidase (GGT), liver injury biomarkers, were also measured. The ROC clearance for HBD was significantly lower than that for LD (0.147 ± 0.052 vs. 0.265 ± 0.148 ml·min ·g liver) after intravenous injection (0.6 mg·kg ). The clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg·kg ·h ), was similar between HBD and LD groups (~ 1 ml·min ·kg ). The TXA clearance in both groups was lower than the GFR, showing a small extent of hepatorenal coupling. The miR-122 and miR-148a expressions were similar for the HBD and LD groups, whereas GGT expression was significantly increased for HBD. The lower ROC clearance and the higher GGT levels in the HBD group of longer cold ischemia times performed worse than the LD group during the neophase. Metabololmics further showed clusters of bile acids, phospholipids and lipid ω-oxidation products for the LD and HBD groups. In conclusion, ROC CL and GGT expression, and metabolomics could serve as sensitive indices of early graft function. Copyright © 2017 John Wiley & Sons, Ltd.

Advances in Solid Phase Microextraction and Perspective on Future Directions

“…For instance, in a recent work, with the aim of evaluating liver and kidney functions of patients recently undergone liver transplantation, pharmacokinetic profiles of tranexamic acid and rocuronium bromide were constructed in plasma samples of recipients of liver transplantation surgery with heart beating or living donors with different cold ischemic times. 389 In addition to tranexamic acid and rocuronium bromide monitoring, the authors performed untargeted analysis of the same samples using HLB coated devices. Despite the small size of the cohort, clustering of samples corresponding to heart beating and living donors in relation to lipid oxidation products and bile acids were observed (Figure 7B).…”

“…Other interesting applications conducted with TFME in its high-throughput format involve targeted and untargeted analyses of biofluid samples, such as plasma, collected at various time points in different patient groups. For instance, in a recent work, with the aim of evaluating liver and kidney functions of patients recently undergone liver transplantation, pharmacokinetic profiles of tranexamic acid and rocuronium bromide were constructed in plasma samples of recipients of liver transplantation surgery with heart beating or living donors with different cold ischemic times . In addition to tranexamic acid and rocuronium bromide monitoring, the authors performed untargeted analysis of the same samples using HLB coated devices.…”

Clinical use of tranexamic acid: evidences and controversies

“…Picetti et al 25 analyzed 21 pharmacodynamics studies of which 20 were in vitro and one was in vivo , and determined the drug plasma levels capable of reducing the activity of tissue plasminogen activator by 80% in vitro (10.ámg.mL -1 ), although other studies have not been able to verify these findings. 26 In the studies by Fillingham et al, 9 , 10 , 18 topical, IV, and oral formulations of TXA were all superior to placebo in terms of reduced blood loss and transfusion risk, while no formulation was clearly superior when compared to each other. The use of repeated doses of oral, IV, topical TXA and higher doses of IV TXA did not significantly reduce blood loss or the risk of transfusion.…”

Recent Advances in Targeting Clinical Volatile Organic Compounds (VOC)

“…In addition to the above-cited applications of SPME fibers, their ability to extract semi-volatile or non-volatile compounds was demonstrated [21,22]. In fact, biofluids including urine, saliva or blood, might comprise many organic compounds which are not present in the vapor phase and hence could not been achieved by headspace analysis [23,24].…”