新型凝血、纤溶标志物在慢性肾脏疾病中的表达变化分析

Changes in the expression of novel coagulation and fibrinolytic markers in chronic kidney disease

摘要:

目的 分析慢性肾病（chronic kidney disease，CKD）患者血浆凝血、纤溶标志物的表达变化趋势，为CKD相关凝血性疾病的诊断和治疗提供依据。方法 从2021年5月到2022年5月就诊于陕西省中医医院的CKD患者和体检人员中根据纳入标准获得CKD患者123名，依据肾小球滤过率（estimated glomerular filtration rate，eGFR）分组，健康体检者40名设为对照组（health control，HC组），分别检测凝血酶调节蛋白（thrombomodulin，TM）、凝血酶-抗凝血酶复合物（thrombin-antithrombin complex，TAT）、纤溶酶-α2抗纤溶酶复合物（plasmin-α₂-antiplasmin complex，PIC）、组织型纤溶酶原激活物抑制剂-1复合物（tissue plasminogen activator inhibitor complex，t-PAIC）、凝血酶原时间（prothrombin time，PT）、活化部分凝血酶原时间（activated partial thromboplastin time，APTT）、凝血酶时间（thrombin time，TT）、纤维蛋白原（fibrinogen，FIB）、纤维蛋白降解产物［fibrin（-ogen） degradation products，FDP］、D-二聚体（D-dimer，DD）水平以及白蛋白、血肌酐（serum creatinine，SCr a）及尿素氮（blood urea nitrogen，BUN）的表达水平。结果 PT、APTT和TT在各组间的差异无统计学意义（P>0.05），CKD组中FIB、DD和TAT高于HC组（P<0.001）；DD在CKD5期高于CKD1、2期（P<0.05）；FDP在CKD2-5期均高于HC组（P<0.05）且CKD5期高于CKD1、2期；PIC在CKD 3-5期高于HC组，CKD4期高于CKD1、2期（P<0.001）；tPAIC在CKD1-4期高于HC组（P<0.05）；TM在CKD2-5期高于HC组，CKD4-5期高于其他分期（P<0.001）；CKD各组TAT/PIC比值高于HC组，CKD1-3组与HC组的差异有统计学意义（P<0.001），TAT/PIC对CKD和HC的鉴别进行受试者工作曲线（receiver operating characteristic curve，ROC）分析，曲线下面积（area under curve，AUC）为0.716。结论 CKD患者体内普遍存在高凝状态，新凝血标志物反映凝血功能变化的能力更优秀。

Abstract:

Objective To investigate the changing trend of the expression of plasma coagulation and fibrinolytic markers in patients with chronic kidney disease（CKD），and to provide a basis for the diagnosis and treatment of CKD-related coagulopathies.Methods According to the inclusion criteria，123 patients with CKD were selected from the CKD patients who attended Shaanxi Provincial Hospital of Traditional Chinese Medicine from May 2021 to May 2022，and they were divided into groups based on estimated glomerular filtration rate；40 healthy controls（HCs） were selected from the individuals who underwent physical examination and were established as HC group. Related coagulation and fibrinolytic markers were measured，i.e.，thrombomodulin（TM），thrombin-antithrombin complex （TAT），fibrin-α2 antifibrinolytic complex（PIC），tissue-type fibrinogen activator inhibitor-1 complex（t-PAIC），prothrombin time （PT），activated partial thromboplastin time（APTT），thrombin time （TT），fibrinogen（FIB），fibrinogen degradation product（FDP），and D-dimer（DD），as well as the expression levels of albumin，serum creatinine（SCr），and blood urea nitrogen（BUN）.Results There were no significant differences in PT，APTT，and TT between groups（P>0.05），and the CKD group had significantly higher FIB，DD，and TAT than the HC group （P<0.001）. The level of DD in stage 5 CKD was significantly higher than that in stage 1/2 CKD（P<0.05）. The level of FDP in stage 2-5 CKD was significantly higher than that in the HCs（P<0.05），and the level of FDP in stage 5 CKD was significantly higher than that in stage 1/2 CKD. PIC in stage 3-5 CKD was significantly higher than that in the HCs，and PIC in stage 4 CKD was significantly higher than that in stage 1/2 CKD（P<0.001）. The level of t-PAIC in stage 1-4 CKD was significantly higher than that in the HCs（P<0.05）. TM in stage 2-5 CKD was significantly higher than that in the HCs，and TM in stage 4-5 CKD was significantly higher than that in the other stages（P<0.001）. The CKD groups had a significantly higher TAT/PIC ratio than the HC group，with a significant difference between stage 1-3 CKD and the HCs（P<0.001）. The receiver operating characteristic（ROC） curve analysis of TAT/PIC ratio showed an area under the ROC curve of 0.716 in differentiating CKD from HCs.Conclusion Hypercoagulability is prevalent in CKD patients，and novel coagulation markers have a good ability to reflect the changes in coagulation function.