Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Al. Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland.
Nephrol Dial Transplant. 2010 Dec;25(12):4061-7. doi: 10.1093/ndt/gfq320. Epub 2010 Jun 8.
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.
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).
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).
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.
花生四烯酸（AA）的活性代谢物，即类二十烷酸，强烈影响肾脏内环境稳定。本研究旨在测量围手术期脂氧合酶（LOX）衍生的 5-、12-和 15-羟二十碳四烯酸（HETE）水平的变化，并检验以下假设：（i）这些花生四烯酸生成动力学在肾移植再灌注的前 5 分钟内是否发生改变，（ii）HETE 酸是否会影响围手术期 20-HETE 的生成，（iii）LOX HETE 是否可以作为移植后早期同种异体移植物功能的标志物。
69 名接受肾移植的患者被分为早期、缓慢和延迟移植物功能（EGF、SGF 和 DGF 组）组。在供体再灌注前和随后的每一分钟采集血液。使用液相色谱法测量 HETE 浓度。在围手术期和随访期间（移植后第一年）测量肌酐水平。
我们的研究结果表明，在所检查的组之间，HETE 变化的浓度和动力学存在显著差异。此外，观察到的 HETE 浓度变化与移植后移植物功能和围手术期 20-HETE 合成密切相关。应用新引入的标志物的截止值，即 5-HETE（5）的 71.72ng/ml、12-HETE△（5-0）的 12.3ng/ml 和 15-HETE△（5-0）的-6.1ng/ml，对 SGF/DGF 的预测灵敏度为 72.5-81.5%，特异性为 50-54%。此外，混合模型分析显示，根据 5-HETE（5）和 15-HETE△（5-0）的结果进行分类的患者在移植后 1 年的同种异体移植物功能方面存在显著差异（P=0.03 和 P<0.05），但在急性排斥反应发作的频率方面无差异（P=0.91 和 P=0.31）。
本研究报告称，人类肾移植会导致 LOX AA 代谢发生显著变化，这强烈影响和预测了早期（1 年）移植后移植物功能。
