血浆D-二聚体水平在抗中性粒细胞胞浆抗体相关性血管炎中的临床意义
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摘要
目的探讨D-二聚体(D-dimer)在抗中性粒细胞胞浆抗体相关性血管炎(anti-neutrophil cytoplasmic antibody-associated vasculitis,AAV)患者中的临床意义。方法回顾性分析2014年5月至2017年11月我院肾内科穿刺活检确诊的50例ANCA相关性血管炎患者的临床资料。采用免疫比浊法检测血浆D-二聚体水平,以其中位数(3.17 mg/L FEU)为截点值将AAV患者分成高低水平2组,低水平组D-dimer<3.17 mg/L FEU,高水平组D-dimer≥3.17 mg/L FEU,比较2组患者临床特征、实验室检查、肾脏病理及预后差异。结果①高水平组患者C反应蛋白(C-reaction protein,CRP)、白细胞介素6(Interleukin-6,IL-6)水平及伯明翰血管炎活动性评分(Birmingham vasculitis activity score,BVAS)高于低水平组(P值分别为0.001、0.015、0.055),24小时尿蛋白定量、血清白蛋白(albumin,Alb)低于低水平组(P值分别为0.031、0.006)。②AAV患者血浆D-二聚体水平与BVAS(r=0.322,P=0.022)、CRP(r=0.573,P<0.001)、IL-6(r=0.341,P=0.015)、肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)(r=0.343,P=0.015)呈正相关。③肾脏病理特征:相较于高水平组患者,低水平组中球性硬化百分比较高(P=0.002),新月体形成的患者较少(P=0.247)。高水平组中细胞性新月体形成的患者数较低水平组多(P=0.017),且百分比高于低水平组(P=0.027)。④血浆D-二聚体(AUC=0.707)评估活动性AAV的预后无统计学差异(P>0.05)。结论血浆D-二聚体水平与AAV患者疾病活动性密切相关,有望成为评估AAV活动性的生物学标志物。
To evaluate the clinical significance of plasma D-dimer levels in anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), total of 50 patients with AAV who underwent renal biopsy were retrospectively analyzed. The levels of plasma D-dimer were determined by immunoturbidimetry, and then AAV patients were divided into low-level group(D-dimer<3.17 mg/L FEU) and high-level group(D-dimer≥3.17 mg/L FEU), with D-dimer median(3.17 mg/L FEU) as a cut-off point. Furthermore, the clinical characters, outcomes of laboratory tests, renal pathology and prognosis of both groups were assessed. Data shown that the levels of Creaction protein(CRP), interleukin-6(IL-6) and Birmingham vasculitis activity score(BVAS) in highlevel group were higher than those in low-level group(P=0.001, 0.015, 0.055); 24-hour proteinuria and serum albumin in high-level group were lower than those in low-level group(P=0.031, 0.006)). The levels of D-dimer were positively correlated with BVAS(r=0.322,P=0.022),CRP(r=0.573, P<0.001), IL-6(r=0.341, P=0.015), and tumor necrosis factor alpha(TNF-α)(r=0.343, P=0.015). Renal pathology analysis shown that a higher percentage of spheroid sclerosis(P=0.002) and fewer patients with crescent formation(P=0.247) in low-level group as compared with the high-level group; the number of patients with cellular crescent formation in the high-level group was higher than that of the low level group(P=0.017), and the percentage was also higher than the low-level group(P=0.027). Diagnostic efficiency of plasma D-dimer levels(AUC=0.707) was a little better than that of serum CRP(AUC=0.700) and IL-6(AUC=0.633) in assessing active AAV patients. There was no significant difference between the two groups in prognosis(P>0.05). Taken together,plasma D-dimer level is closely related to AAV activity and might be a biomarker in assessment of AAV activity.
To evaluate the clinical significance of plasma D-dimer levels in anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), total of 50 patients with AAV who underwent renal biopsy were retrospectively analyzed. The levels of plasma D-dimer were determined by immunoturbidimetry, and then AAV patients were divided into low-level group(D-dimer<3.17 mg/L FEU) and high-level group(D-dimer≥3.17 mg/L FEU), with D-dimer median(3.17 mg/L FEU) as a cut-off point. Furthermore, the clinical characters, outcomes of laboratory tests, renal pathology and prognosis of both groups were assessed. Data shown that the levels of Creaction protein(CRP), interleukin-6(IL-6) and Birmingham vasculitis activity score(BVAS) in highlevel group were higher than those in low-level group(P=0.001, 0.015, 0.055); 24-hour proteinuria and serum albumin in high-level group were lower than those in low-level group(P=0.031, 0.006)). The levels of D-dimer were positively correlated with BVAS(r=0.322,P=0.022),CRP(r=0.573, P<0.001), IL-6(r=0.341, P=0.015), and tumor necrosis factor alpha(TNF-α)(r=0.343, P=0.015). Renal pathology analysis shown that a higher percentage of spheroid sclerosis(P=0.002) and fewer patients with crescent formation(P=0.247) in low-level group as compared with the high-level group; the number of patients with cellular crescent formation in the high-level group was higher than that of the low level group(P=0.017), and the percentage was also higher than the low-level group(P=0.027). Diagnostic efficiency of plasma D-dimer levels(AUC=0.707) was a little better than that of serum CRP(AUC=0.700) and IL-6(AUC=0.633) in assessing active AAV patients. There was no significant difference between the two groups in prognosis(P>0.05). Taken together,plasma D-dimer level is closely related to AAV activity and might be a biomarker in assessment of AAV activity.
引文
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[17]Zonozi R,Niles JL,Cortazar FB.Renal involvement in antineutrophil cytoplasmic antibody-associated vasculitis[J].Rheum Dis Clin North Am,2018,44(4):525-543.
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[19]Stassen PM,Derks RP,Kallenberg CG,et al.Venous thromboembolism in ANCA-associated vasculitisincidence and risk factors[J].Rheumatology(Oxford),2008,47(4):530-534.
[2]Berti A,Cavalli G,Campochiaro C,et al.Interleukin-6 in ANCA-associated vasculitis:Rationale for successful treatment with tocilizumab[J].Semin Arthritis Rheum,2015,45(1):48-54.
[3]Kronbichler A,Kerschbaum J,Grundlinger G,et al.Evaluation and validation of biomarkers in granulomatosis with polyangiitis and microscopic polyangiitis[J].Nephrol Dial Transplant,2016,31(6):930-936.
[4]Castelli R,Gallipoli P,Schiavon R,et al.High prevalence of heparin induced thrombocytopenia with thrombosis among patients with essential thrombocytemia carrying V617F mutation[J].J Thromb Thrombolysis,2018,45(1):106-113.
[5]Kyrle PA,Eichinger S.D-Dimer for long-term risk prediction in patients after acute coronary syndrome[J].Circulation,2018,138(7):724-726.
[6]Tan L,Wang Q,Zeng T,et al.Clinical significance of detecting HLA-DR,14-3-3eta protein and d-dimer in the diagnosis of rheumatoid arthritis[J].Biomark Med,2018,12(7):697-705.
[7]Sewify EM,Sayed D,Abdel Aal RF,et al.Increased circulating red cell microparticles(RMP)and platelet microparticles(PMP)in immune thrombocytopenic purpura[J].Thromb Res,2013,131(2):e59-63.
[8]Liang Y,Xie SB,Wu CH,et al.Coagulation cascade and complement system in systemic lupus erythematosus[J].Oncotarget,2018,9(19):14862-14881.
[9]Heller I,Isakov A,Topilsky M.American College of Rheumatology Criteria for the diagnosis of vasculitis[J].Ann Intern Med,1999,130(10):861-862.
[10]Mukhtyar C,Lee R,Brown D,et al.Modification and validation of the Birmingham vasculitis activity score(version 3)[J].Ann Rheum Dis,2009,68(12):1827-1832.
[11]唐莎,张静波.ANCA相关性血管炎的免疫发病机制新进展[J].免疫学学杂志,2013,29(7):628-631.
[12]Masuda T,Shoko T,Deguchi Y.Clinical investigation of coagulation markers for early detection of sepsis-induced disseminated intravascular coagulation:a single-center,prospective observational study[J].Clin Appl Thromb Hemost,2018,24(7):1082-1087.
[13]Simes J,Robledo KP,White HD,et al.D-dimer predicts long-term cause-specific mortality,cardiovascular events,and cancer in patients with stable coronary heart disease[J].Circulation,2018,138(7):712-723.
[14]You LR,Tang M.The association of high D-dimer level with high risk of ischemic stroke in nonvalvular atrial fibrillation patients:A retrospective study[J].Medicine(Baltimore),2018,97(43):e12622.
[15]Ma TT,Huang YM,Wang C,et al.Coagulation and fibrinolysis index profile in patients with ANCA-associated vasculitis[J].PLoS One,2014,9(5):e97843.
[16]贺江花,张瑞,谢丽娇,等.TNF-α水平在抗中性粒细胞胞浆抗体相关性血管炎中的临床意义[J].免疫学杂志,2017,33(12):1060-1065.
[17]Zonozi R,Niles JL,Cortazar FB.Renal involvement in antineutrophil cytoplasmic antibody-associated vasculitis[J].Rheum Dis Clin North Am,2018,44(4):525-543.
[18]Chen YX,Chen XN.Antineutrophil cytoplasmic antibodies-associated glomerulonephritis:From bench to bedside[J].Chronic Dis Transl Med,2018,4(3):187-191.
[19]Stassen PM,Derks RP,Kallenberg CG,et al.Venous thromboembolism in ANCA-associated vasculitisincidence and risk factors[J].Rheumatology(Oxford),2008,47(4):530-534.
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