Non-isotopic tyrosine kinetics using an alanyl-tyrosine dipeptide to assess graft function in liver transplant recipients - a pilot study.
BACKGROUND
Although accurate assessment of liver function in liver transplant recipients is of crucial importance for optimal timing of the procedure and for determining graft viability, none of the many available methods has proven reliable in the clinical routine. Thus, a novel non-isotopic assay of tyrosine kinetics using the tyrosine-containing dipeptide L-alanyl-L-tyrosine (Ala-Tyr) was tested for its clinical feasibility in patients undergoing orthotopic liver transplantation (OLT).


METHODS
Plasma levels of tyrosine and clearance of tyrosine released after infusion of the dipetide Ala-Tyr were assessed before and one day after OLT in 10 liver transplant recipients with normal graft function, also in three organ donors and in three recipients showing poor graft function. Standard laboratory parameters (e.g. aminotransferases) and the plasma disappearance rate of indocyanine green were also measured.


RESULTS
Following uneventful OLT, tyrosine plasma levels (before 127 +/- 15 micromol/vs. post-OLT 52 +/- 6 micromol/l, P < 0.05) and kinetics (tyrosine clearance: before 206 +/- 77 ml/min vs. post-OLT 371 +/- 109 ml/min, P < 0.05) were normalized. In cases of severe graft dysfunction, tyrosine kinetics (tyrosine clearance: 238 +/- 61 ml/min) resembled the situation in end-stage liver disease, whereas no such correlation was seen with conventional markers of liver function. Organ preservation had only a minor impact on tyrosine kinetics (n.s.).


CONCLUSIONS
OLT rapidly normalizes both the plasma levels and the kinetics of tyrosine. Graft failure is associated with an immediate rise in plasma tyrosine levels and a delay in tyrosine elimination. Our results show that tyrosine clearance using the dipetide Ala-Tyr is a suitable non-isotopic, non-invasive indicator of graft viability in the early postoperative course following OLT.
Krenn
Claus G
CG
Department of Anesthesiology and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria. claus.krenn@meduniwien.ac.at
Pokorny
Herwig
H
Hoerauf
Klaus
K
Stark
Josef
J
Roth
Erich
E
Steltzer
Heinz
H
Druml
Wilfred
W
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D004151:Dipeptides; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D017093:Liver Failure / Q000097:blood / Q000175:diagnosis; D008111:Liver Function Tests / Q000379:methods*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D014019:Tissue Donors; D014443:Tyrosine / Q000097:blood*
D004151:Dipeptides; C016968:alanyltyrosine; D014443:Tyrosine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007208:Indocyanine Green