【摘要】目的探讨双膜血浆置换对需肾替代治疗的抗中性粒细胞胞浆抗体相关性血管炎的疗效及对生存率的影响。方法纳入2015 年1月～2017 年3月在自贡市第一人民医院确诊为抗中性粒细胞胞浆抗体(anti-neutrophil cytoplasm antibody, ANCA)相关性血管炎的患者25例，确诊时即需要肾替代治疗，随机分为接受激素联合环磷酰胺免疫抑制治疗+双膜血浆置换(double-filtration plasmapheresis, DFPP)治疗的DFPP 组(12 例)和只接受激素联合环磷酰胺免疫抑制治疗的对照组(13 例)，分析入组时患者一般情况，测定2 组患者治疗前后的ANCA、IgG 水平，记录随访12 个月患者的存活情况。结果DFPP组治疗后髓过氧化物酶抗体(myeloperoxidase-ANCA,MPO-ANCA)及IgG 水平较治疗前明显下降,下降率分别为53.2%(t=12.131，P＜0.001),47.4%(t=10.798,P＜0.001)。对照组治疗后MPO-ANCA 水平较治疗前下降16.7%(t=10.319，P=0.069)，对照组治疗后IgG 水平较治疗前下降14.1%(t=10.134，P=0.035)。DFPP 组治疗后IgG 水平与对照组治疗后相比下降33.8%，差异有统计学意义(t=5.334，P=0.012)。随访12 个月，累计存活率DFPP 组为61.5%，对照组为58.3%(c2=0.193，P=0.046)，2 组中存活患者均未摆脱透析。结论双膜血浆置换能有效降低患者IgG 及MPO-ANCA 抗体水平，提高患者1 年存活率，但不能有效提高患者的摆脱透析率。
【Abstract】Objective The objective of this study was to investigate the effect of double-filtration plasmapheresis (DFPP) therapy on anti- neutrophil cytoplasmic antibody (ANCA)- associated vasculitis that requires renal replacement therapy (RRT) and its effect on survival rate. Methods A total of 25 patients with ANCA-associated vasculitis diagnosed in the First People's Hospital of Zigong from January 2015 to March 2017 were enrolled in this study. RRT was required at the time of diagnosis. Patients were randomly divided into the DFPP group (n=12) and the control group (n=13). Both groups received glucocorticoid and cyclophosphamide
immunosuppressive therapy; the DFPP group also treated with DFPP therapy. Demographic data and clinical parameters of the patients were collected. ANCA and IgG levels were measured before and after DFPP therapy for three times. Their survival rate was calculated after follow-up for 12 months. Results In the DFPP group, myeloperoxidase (MPO)- ANCA and IgG levels after the treatment decreased by 53.2% (t=12.131, P＜0.001) and 47.4% (t=10.798, P＜0.001) respectively. In the control group, MPO-ANCA level after the treatment decreased 16.7% (t=10.319, P=0.069), and IgG level decreased by 14.1% (t=10.134, P=0.035). In the DFPP group, IgG level decreased by 33.8% as compared with that in the control group (t=5.334, P=0.012). During the follow-up period of 12 months, the cumulative survival rate was 61.5% in the DFPP group and 58.3% in the control group (c2= 0.193, P=0.046). All survival patients still relied on dialysis during the follow-up study. Conclusion DFPP can effectively reduce the levels of IgG and MPO-ANCA and improve one year survival rate. However, DFPP cannot change dialysis dependence of the patients.
1. Jennette JC, Falk RJ, Bacon PA et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides [J]. Arthritis Rheum 2013; 65: 1-11.
2. Lardinois OM, Deterding LJ, Hess JJ et al. Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity [J]. PLoS One 2019; 14: e0213215.
3. Noone D, Hebert D, Licht C. Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement [J]. Pediatr Nephrol 2018; 33: 1-11.
4. Gorka J, Polok K, Nowak I et al. Effectiveness of plasmapheresis in ANCA clearance in patients with ANCA-associated vasculitides [J]. Przegl Lek 2016; 73: 445-447.
5. Chen Y, Yang L, Li K et al. Double Filtration Plasmapheresis in the Treatment of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis With Severe Renal Failure: A Preliminary Study of 15 Patients [J]. Ther Apher Dial 2016; 20: 183-188.
6. Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom [J]. Arthritis Rheum 2000; 43: 414-419.
7. Shi L. Anti-neutrophil cytoplasmic antibody-associated vasculitis: prevalence, treatment, and outcomes [J]. Rheumatol Int 2017; 37: 1779-1788.
8. Chen M, Yu F, Zhang Y, Zhao MH. Clinical and pathological characteristics of Chinese patients with antineutrophil cytoplasmic autoantibody associated systemic vasculitides: a study of 426 patients from a single centre [J]. Postgrad Med J 2005; 81: 723-727.
9. Chang DY, Li ZY, Chen M, Zhao MH. Myeloperoxidase-ANCA-positive granulomatosis with polyangiitis is a distinct subset of ANCA-associated vasculitis: A retrospective analysis of 455 patients from a single center in China [J]. Semin Arthritis Rheum 2019; 48: 701-706.
10. Dhaun N, Saunders A, Bellamy CO et al. Benefits of an expanded use of plasma exchange for anti-neutrophil cytoplasmic antibody-associated vasculitis within a dedicated clinical service [J]. BMC Musculoskelet Disord 2015; 16: 343.
11. Emejuaiwe N. Treatment Strategies in ANCA-Associated Vasculitis [J]. Curr Rheumatol Rep 2019; 21: 33.
12. Alamartine E, Maillard N. Therapeutic plasma exchange in nephrology. Where it applies? [J] Transfus Apher Sci 2019; 58: 262-265.
13. Puechal X. Targeted immunotherapy strategies in ANCA-associated vasculitis. Joint Bone Spine 2019 [J]; 86: 321-326.
14. Yates M, Watts RA, Bajema IM et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis [J]. Ann Rheum Dis 2016; 75: 1583-1594.
15. Jennette JC, Falk RJ. B cell-mediated pathogenesis of ANCA-mediated vasculitis [J]. Semin Immunopathol 2014; 36: 327-338.
16. Gong D, Ji D, Xu B, Liu Z. More selective removal of myeloperoxidase-anti-neutrophil cytoplasmic antibody from the circulation of patients with vasculitides using a novel double-filtration plasmapheresis therapy [J]. Ther Apher Dial 2013; 17: 93-98.
17. Apaydin S. The treatment of ANCA-associated rapidly-progressive glomerulonephritis and Goodpasture syndrome with therapeutic apheresis [J]. Transfus Apher Sci 2018; 57: 8-12.
18. Walsh M, Casian A, Flossmann O et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear [J]. Kidney Int 2013; 84: 397-402.
19. Xu PC, Chen T, Wu SJ et al. Pathological severity determines the renal recovery for anti-myeloperoxidase antibody-associated vasculitis requiring dialysis at disease onset: a retrospective study. BMC Nephrol 2019 [J]; 20: 287.
20. Kristensen T, Gregersen JW, Krag SR, Ivarsen P. The relation between histopathological classification and renal outcome, ANCA subtype and treatment regimens in ANCA-associated vasculitis [J]. Clin Exp Rheumatol 2016; 34: S105-110.
21. Solar-Cafaggi D, Atisha-Fregoso Y, Hinojosa-Azaola A. Plasmapheresis therapy in ANCA-associated vasculitides: A single-center retrospective analysis of renal outcome and mortality [J]. J Clin Apher 2016; 31: 411-418.
22. 陈樱花, 刘霞, 刘正钊 et al. 需肾脏替代治疗的ANCA相关肾炎患者的预后及其影响因素 [J]. 中华医学杂志 2018; 98: 274-279.
23. Walsh M, Merkel PA, Peh CA et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial [J]. Trials 2013; 14: 73.
