Exploration on role of peripheral blood FAR and Lp-PLA2 in thrombotic susceptibility of patients with idiopathic membranous nephropathy
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摘要: 目的 探讨特发性膜性肾病(idiopathic membranous nephropathy，IMN)患者外周血纤维蛋白原/白蛋白比值(fibrinogen/albumin ratio，FAR)、脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2，Lp-PLA2)水平，分析其对IMN并发血栓的预测价值。方法 选取2020年1月—2023年1月医院收治的60例IMN并发血栓患者作为研究组，另选同期60例IMN无血栓患者作为对照组。比较2组一般资料、24 h尿蛋白定量(24 h Upro)、血脂指标(甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇)、凝血功能指标[凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(FIB)、活化部分凝血酶原时间(APTT)]、外周血FAR、Lp-PLA2水平。logistic回归分析IMN并发血栓的影响因素。分析研究组外周血FAR、Lp-PLA2水平与IMN并发血栓影响因素的相关性。对比分析含与不含外周血FAR、Lp-PLA2预测方案对IMN并发血栓的预测价值。结果 2组IMN病程、病理分期、24 h Upro、外周血D-D、FIB、APTT、FAR、Lp-PLA2水平比较差异有统计学意义(P < 0.05)；IMN病程、病理分期、24 h Upro、外周血D-D、FIB、APTT、FAR、Lp-PLA2水平为IMN并发血栓的影响因素(P < 0.05)；外周血FAR、Lp-PLA2联合预测IMN并发血栓的受试者工作特征曲线下面积(AUC)大于单项指标预测(P < 0.05)；含FAR、Lp-PLA2预测方案对IMN并发血栓的预测效果较不含FAR、Lp-PLA2预测方案明显改善(P < 0.05)。结论 IMN并发血栓患者外周血FAR、Lp-PLA2水平升高，且与血栓易感性密切相关，含外周血FAR、Lp-PLA2预测方案对IMN并发血栓具有一定预测价值。
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关键词:
- 特发性膜性肾病 /
- 纤维蛋白原 /
- 白蛋白 /
- 脂蛋白相关磷脂酶A2
Abstract: Objective To investigate the levels of fibrinogen/albumin ratio(FAR) and lipoprotein-associated phospholipase A2(Lp-PLA2) in peripheral blood of patients with idiopathic membranous nephropathy(IMN), and analyze their predictive value for thrombosis in IMN.Methods Sixty patients with IMN complicated by thrombosis admitted to the hospital from January 2020 to January 2023 were selected as the study group, and another 60 patients with IMN without thrombosis in the same period were selected as the control group. The general data, 24 h urine protein quantification(24 h Upro), lipid indexes(triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), coagulation indexes(D-dimer[D-D], prothrombin time[TT], prothrombin time[PT], fibrinogen[FIB]) were compared between the two groups. Logistic regression was used to analyze the factors influencing the complication of thrombosis in IMN. The correlation between peripheral blood FAR and Lp-PLA2 levels in the study group and the factors affecting IMN complicating thrombosis was analyzed. The predictive value of the prediction scheme with and without peripheral blood FAR and Lp-PLA2 for IMN complicating thrombosis was compared.Results There were significant differences in IMN course, pathological stage, 24 h Upro, peripheral blood D-D, FIB, APTT, FAR and Lp-PLA2 levels between the two groups(P < 0.05). The course of IMN disease, pathological stage, 24 h Upro, peripheral blood D-D, FIB, APTT, FAR and Lp-PLA2 levels were the influencing factors of IMN complicated with thrombus(P < 0.05). The AUC of peripheral blood FAR and Lp-PLA2 combined predicted thrombus of IMN was greater than that of single index(P < 0.05). The prediction effect of FAR and Lp-PLA2 prediction schemes on thrombosis complicated by IMN was significantly improved compared with that without FAR and Lp-PLA2 prediction schemes(P < 0.05).Conclusion The levels of FAR and Lp-PLA2 in peripheral blood of patients with IMN complicated with thrombus were increased, which was closely related to the susceptibility to thrombus. The prediction scheme including peripheral blood FAR and Lp-PLA2 might have a certain value in predicting thrombus complicated with IMN. -
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表 1 2组一般资料及实验室指标比较
项目 研究组(n=60) 对照组(n=60) t/χ2/u P 性别/例(%) 0.556 0.456 男 38(63.33) 34(56.67) 女 22(36.67) 26(43.33) 年龄/岁 46.12±8.41 43.79±8.25 1.532 0.128 IMN病程/年 4.11±0.93 2.86±0.77 8.019 ＜0.001 BMI 23.75±2.16 23.21±1.94 1.441 0.152 病理分期/例(%) 8.124 0.017 Ⅰ期 20(33.33) 33(55.00) Ⅱ期 22(36.67) 20(33.33) Ⅲ期 18(30.00) 7(11.67) 饮酒史/例(%) 0.519 0.471 有 12(20.00) 9(15.00) 无 48(80.00) 51(85.00) 吸烟史/例(%) 0.786 0.375 有 15(25.00) 11(18.33) 无 45(75.00) 49(81.67) 高血压/例(%) 0.891 0.345 有 13(21.67) 9(15.00) 无 47(78.33) 51(85.00) 糖尿病/例(%) 0.563 0.453 有 11(18.33) 8(13.33) 无 49(81.67) 52(86.67) 激素治疗/例(%) 0.686 0.408 是 9(15.00) 6(10.00) 否 51(85.00) 54(90.00) 24 h Upro/(g/24 h) 5.63±1.35 3.41±0.82 10.887 ＜0.001 TG/(mmol/L) 3.03±0.85 2.81±0.79 1.469 0.145 TC/(mmol/L) 9.72±2.86 9.25±2.49 0.960 0.339 HDL-C/(mmol/L) 1.47±0.39 1.52±0.43 0.667 0.506 LDL-C/(mmol/L) 5.26±1.18 4.87±1.04 1.921 0.057 D-D/(μg/mL) 0.61±0.07 0.30±0.04 29.784 ＜0.001 TT/s 30.17±5.26 29.40±4.93 0.827 0.410 PT/s 12.85±0.91 12.56±0.88 1.774 0.079 FIB/(g/L) 7.15±1.94 4.62±1.25 8.492 ＜0.001 APTT/s 36.71±4.25 30.96±3.88 7.740 ＜0.001 FAR 1.12±0.21 0.95±0.17 4.874 ＜0.001 Lp-PLA2/(U/L) 663.91±95.42 71.02±16.45 47.430 ＜0.001 
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表 2 赋值方法
变量 赋值 因变量 并发血栓 否=0，是=1 自变量 IMN病程 连续变量，原值代入 病理分期 Ⅰ期=1，Ⅱ期=2，Ⅲ期=3 24 h Upro 连续变量，原值代入 D-D 连续变量，原值代入 FIB 连续变量，原值代入 APTT 连续变量，原值代入 FAR 连续变量，原值代入 Lp-PLA2 连续变量，原值代入
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表 3 IMN并发血栓的影响因素分析
变量 β SE Wald χ2 OR 95%CI P 下限 上限 IMN病程 1.377 0.425 10.499 3.963 1.241 12.657 < 0.001 病理分期 1.779 0.451 15.558 5.923 2.013 17.429 < 0.001 24 h Upro 1.618 0.429 14.230 5.045 1.684 15.112 < 0.001 D-D 1.538 0.433 12.619 4.656 1.507 14.385 < 0.001 FIB 1.475 0.426 11.991 4.372 1.446 13.217 < 0.001 APTT 1.561 0.398 15.387 4.765 1.513 15.004 < 0.001 FAR 1.879 0.418 20.215 6.549 2.216 19.357 < 0.001 Lp-PLA2 1.827 0.426 18.394 6.215 2.108 18.326 < 0.001
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表 4 FAR、Lp-PLA2与IMN并发血栓影响因素的相关性
指标 IMN病程 病理分期 24 h Upro D-D FIB APTT FAR r 0.215 0.208 0.119 0.224 0.196 0.209 P 0.139 0.145 0.412 0.120 0.152 0.142 Lp-PLA2 r 0.228 0.235 0.131 0.233 0.210 0.218 P 0.117 0.126 0.357 0.105 0.131 0.129
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表 5 FAR、Lp-PLA2预测IMN并发血栓的价值
指标 AUC 95%CI 截断值 敏感度 特异度 P FAR 0.717 0.628~0.796 1.05 0.716 7 0.666 7 < 0.001 Lp-PLA2 0.726 0.637~0.804 420.15 U/L 0.751 2 0.667 3 < 0.001 联合预测 0.855 0.780~0.913 - 0.733 5 0.866 9 < 0.001
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表 6 含与不含FAR、Lp-PLA2预测方案对IMN并发血栓的预测价值比较
成对对比 AUC差异(95%CI) NRI(95%CI) IDI(95%CI) 含FAR、Lp-PLA2预测方案vs不含FAR、Lp-PLA2预测方案 0.077(0.005~0.150) 0.864(0.226~1.157) 0.213(0.056~0.351) P 0.037 0.009 0.015
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