Naumnik Beata, Borawski Jacek, Pawlak Krystyna, Mysliwiec Michal
Department of Nephrology and Transplantation with Dialysis Unit, Medical University, 14 Zurawia Street, 15-540 Białystok, Poland.
Nephrol Dial Transplant. 2007 Jun;22(6):1690-6. doi: 10.1093/ndt/gfm082. Epub 2007 Mar 26.
Transforming growth factor-beta1 (TGF-beta1) is a multi-functional cytokine that presents as a mediator of the heparin's pleiotropic action. In this cross-over study, we compared the effects of enoxaparin and unfractionated heparin (UFH) used as anticoagulants during haemodialysis (HD) on plasma TGF-beta1 levels and some platelet activation markers: platelet-derived growth factor-AB (PDGF-AB), beta-thromboglobulin (beta-TG) and platelet factor-4 (PF-4).
Plasma immunoreactive markers (in 22 chronically HD patients) were quantified at the start, at 10 and 180 min of HD session. Enoxaparin was administered as a single dose of 0.67 +/- 0.14 mg/kg at the onset of HD, while UFH was given as a bolus of 1500 (500-3500) IU followed by an infusion of 2750 (1500-6500) IU. The time of evaluation for each heparin was 3 months.
Pre-dialysis, TGF-beta1 levels tended to be lower in patients anticoagulated with enoxaparin compared with UFH [6.9 (3.3-21.9) ng/ml vs 8.4 (3.8-30.2) ng/ml, respectively; P = 0.05]. Overdialysis, TGF-beta1 levels showed a significant 44.8% increase to 10.0 (2.9-28.0) ng/ml after 10 min (P = 0.002) and to 9.32 (5.3-23.7) ng/ml after 180 min (P = 0.016) of enoxaparin-anticoagulated HD and remained stable during UFH administration [9.4 (3.9-25.3) ng/ml after 10 min, 8.1 (4.1-21.9) ng/ml after 180 min; P = 0.385]. The 35% increase in plasma TGF-beta1 after 180 min of HD positively correlated with the enoxaparin dose/kg (r = 0.553, P = 0.008) and, interestingly, negatively with the baseline level of the cytokine (r = -0.544, P = 0.009). Despite a positive correlation between TGF-beta1 and PDGF-AB during HD, there were no associations between TGF-beta1 and beta-TG or PF-4 regardless of the type of anticoagulation.
Enoxaparin, compared with UFH, induces a rapid overdialytic but not sustained increase in plasma TGF-beta1 levels. The effect is closely dose-dependent and may reflect systemic activation of this multi-potential cytokine.
转化生长因子-β1（TGF-β1）是一种多功能细胞因子，是肝素多效性作用的介质。在这项交叉研究中，我们比较了血液透析（HD）期间用作抗凝剂的依诺肝素和普通肝素（UFH）对血浆TGF-β1水平及一些血小板活化标志物的影响：血小板衍生生长因子-AB（PDGF-AB）、β-血小板球蛋白（β-TG）和血小板因子4（PF-4）。
在HD治疗开始时、10分钟和180分钟时对22例慢性HD患者的血浆免疫反应性标志物进行定量。HD开始时，依诺肝素以0.67±0.14mg/kg的单剂量给药，而UFH以1500（500-3500）IU的推注剂量给药，随后以2750（1500-6500）IU的输注剂量给药。每种肝素的评估时间为3个月。
透析前，与UFH抗凝的患者相比，依诺肝素抗凝的患者TGF-β1水平往往较低[分别为6.9（3.3-21.9）ng/ml和8.4（3.8-30.2）ng/ml；P=0.05]。透析期间，依诺肝素抗凝的HD在10分钟后TGF-β1水平显著升高44.8%，达到10.0（2.9-28.0）ng/ml（P=0.002），180分钟后达到9.32（5.3-23.7）ng/ml（P=0.016），而在UFH给药期间保持稳定[10分钟后为9.4（3.9-25.3）ng/ml，180分钟后为8.1（4.1-21.9）ng/ml；P=0.385]。HD 180分钟后血浆TGF-β1升高35%与依诺肝素剂量/千克呈正相关（r=0.553，P=0.008），有趣的是，与细胞因子的基线水平呈负相关（r=-0.544，P=0.009）。尽管HD期间TGF-β1与PDGF-AB之间呈正相关，但无论抗凝类型如何，TGF-β1与β-TG或PF-4之间均无关联。
与UFH相比，依诺肝素可导致血浆TGF-β1水平在透析期间迅速升高，但不会持续升高。这种效应与剂量密切相关，可能反映了这种多潜能细胞因子的全身激活。
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