Lipoxygenase-derived hydroxyeicosatetraenoic acids--novel perioperative markers of early post-transplant allograft function?
BACKGROUND
Active metabolites of arachidonic acid (AA), eicosanoids, strongly influence renal homeostasis. The aims of this study were to measure perioperative variations in lipoxygenase (LOX)-derived 5-, 12- and 15-hydroxyeicosatetraenoic (HETE) acids levels, and to examine whether (i) dynamics of these eicosanoid generation changes during the first 5 min of renal allograft reperfusion, (ii) examined HETE acids may influence perioperative 20-HETE generation, and (iii) LOX HETE may serve as perioperative markers of early post-transplant allograft function.


METHODS
Sixty-nine kidney recipients were divided into early, slow and delayed graft function (EGF, SGF and DGF, respectively) groups. Blood was taken directly before, and in the consecutive minutes of graft reperfusion. HETE concentrations were measured using liquid chromatography. Creatinine levels were measured during the perioperative period, as well as during follow-up visits (first post-transplant year).


RESULTS
Our results demonstrated significant differences in the concentrations and dynamics of HETE changes between the examined groups. Moreover, observed changes in HETE concentrations were strongly associated with post-transplant graft function and perioperative 20-HETE synthesis. Application of cut-off limits for newly introduced markers, that is 71.72 ng/mL for 5-HETE(5), 12.3 ng/mL for 12-HETE△(5-0) and -6.1 ng/mL for 15-HETE△(5-0), resulted in 72.5-81.5% sensitivity and 50-54% specificity for SGF/DGF prediction. Moreover, mixed model analysis revealed that recipients classified according to results of 5-HETE(5) and 15-HETE△(5-0) significantly differ in 1-year post-transplant allograft function (P  =  0.03 and P  < 0.05, respectively), however, not in the frequency of acute rejections' episodes (P = 0.91 and P = 0.31, respectively).


CONCLUSIONS
We hereby report that human kidney transplantations are accompanied by significant changes in LOX AA metabolism, which strongly influences and predicts early (1 year) post-transplant graft function.
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Al. Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland.
Barbara
B
Dolegowska
Wojciech
W
Blogowski
Krzysztof
K
Safranow
Leszek
L
Domanski
Katarzyna
K
Jakubowska
Maria
M
Olszewska
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D016030:Kidney Transplantation / Q000502:physiology*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059035:Perioperative Period; D012189:Retrospective Studies; D013997:Time Factors; D014184:Transplantation, Homologous
D015415:Biomarkers; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D008084:Lipoxygenase