Pawlak Krystyna, Tankiewicz Janina, Mysliwiec Michal, Pawlak Dariusz
Department of Monitored Pharmacotherapy, 15-089 Bialystok, Poland.
Blood Coagul Fibrinolysis. 2009 Oct;20(7):590-4. doi: 10.1097/MBC.0b013e32832da16d.
The abnormalities of tissue factor (TF) and its inhibitor (TFPI) system could potentially contribute to high incidence of thrombotic complications and atherosclerosis in patients with chronic kidney disease (CKD). Recently, the role of the kynurenine (KYN) pathway of tryptophan (TRP) degradation has been postulated in the progression of cardiovascular complications. We compared the plasma TF, TFPI and the metabolites of TRP degradation: KYN and 3-hydroxykynurenine (3-HKYN) levels in 55 CKD patients on conservative treatment and 19 healthy controls; and we tried to establish whether or not there is an association between TF/TFPI system and above-mentioned metabolites in these patients. Compared with the controls, the patients with CKD showed a significant increase in plasma concentrations of TF (P < 0.01), KYN, 3-HKYN (both P < 0.0001), KYN-to-TRP (kyn/trp) ratio (P < 0.001) and 3-HKYN-to-KYN (3-hkyn/kyn) ratio (P < 0.05). In contrast, TRP concentrations were significantly decreased in the CKD group compared with controls (P < 0.001). The difference in TFPI levels between CKD patients and controls was not statistically significant. TF/TFPI system was inversely correlated with TRP, whereas it was positively related to the 3-HKYN, kyn/trp and 3-hkyn/kyn ratios. Moreover, both the TF/TFPI system and KYNs were associated with the markers of kidney function. These data suggested for the first time a significant relationship between TF/TFPI system and KYN pathway in CKD patients on conservative treatment.
组织因子(TF)及其抑制剂(TFPI)系统的异常可能是导致慢性肾脏病(CKD)患者血栓并发症和动脉粥样硬化高发的潜在原因。最近,色氨酸(TRP)降解的犬尿氨酸(KYN)途径在心血管并发症进展中的作用已得到推测。我们比较了55例接受保守治疗的CKD患者和19例健康对照者的血浆TF、TFPI以及TRP降解代谢产物:KYN和3-羟基犬尿氨酸(3-HKYN)水平;并试图确定这些患者中TF/TFPI系统与上述代谢产物之间是否存在关联。与对照组相比,CKD患者的血浆TF浓度显著升高(P < 0.01),KYN、3-HKYN(均P < 0.0001)、KYN与TRP的比值(kyn/trp)(P < 0.001)以及3-HKYN与KYN的比值(3-hkyn/kyn)(P < 0.05)均显著升高。相反,CKD组的TRP浓度与对照组相比显著降低(P < 0.001)。CKD患者与对照组之间的TFPI水平差异无统计学意义。TF/TFPI系统与TRP呈负相关,而与3-HKYN、kyn/trp和3-hkyn/kyn比值呈正相关。此外,TF/TFPI系统和KYNs均与肾功能指标相关。这些数据首次表明在接受保守治疗的CKD患者中,TF/TFPI系统与KYN途径之间存在显著关系。