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-1·g-1 liver) after intravenous injection (0.6 mg·kg-1). The clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg·kg-1·h-1), was similar between HBD and LD groups (~ 1 ml·min-1·kg-1). 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.
| Original language | English (US) |
|---|---|
| Journal | Biopharmaceutics and Drug Disposition |
| DOIs | |
| State | Accepted/In press - 2017 |
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Keywords
- Biomarkers and metabolomics
- Heart beating and living donors
- Liver and kidney function
- Liver transplantation
- Rocuronium bromide and tranexamic acid clearance
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Pharmacology (medical)
Cite this
Comparing early liver graft function from heart beating and living-donors : A pilot study aiming to identify new biomarkers of liver injury. / Yang, Qi Joy; Kluger, Michael; Goryński, Krzysztof; Pawliszyn, Janusz; Bojko, Barbara; Yu, Aiming; Noh, Keumhan; Selzner, Markus; Jerath, Angela; Mccluskey, Stuart; Pang, K. Sandy; Wasowicz, Marcin.
In: Biopharmaceutics and Drug Disposition, 2017.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Comparing early liver graft function from heart beating and living-donors
T2 - A pilot study aiming to identify new biomarkers of liver injury
AU - Yang, Qi Joy
AU - Kluger, Michael
AU - Goryński, Krzysztof
AU - Pawliszyn, Janusz
AU - Bojko, Barbara
AU - Yu, Aiming
AU - Noh, Keumhan
AU - Selzner, Markus
AU - Jerath, Angela
AU - Mccluskey, Stuart
AU - Pang, K. Sandy
AU - Wasowicz, Marcin
PY - 2017
Y1 - 2017
N2 - 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-1·g-1 liver) after intravenous injection (0.6 mg·kg-1). The clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg·kg-1·h-1), was similar between HBD and LD groups (~ 1 ml·min-1·kg-1). 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.
AB - 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-1·g-1 liver) after intravenous injection (0.6 mg·kg-1). The clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg·kg-1·h-1), was similar between HBD and LD groups (~ 1 ml·min-1·kg-1). 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.
KW - Biomarkers and metabolomics
KW - Heart beating and living donors
KW - Liver and kidney function
KW - Liver transplantation
KW - Rocuronium bromide and tranexamic acid clearance
UR - http://www.scopus.com/inward/record.url?scp=85017402870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017402870&partnerID=8YFLogxK
U2 - 10.1002/bdd.2066
DO - 10.1002/bdd.2066
M3 - Article
C2 - 28102538
AN - SCOPUS:85017402870
JO - Biopharmaceutics and Drug Disposition
JF - Biopharmaceutics and Drug Disposition
SN - 0142-2782
ER -