蛋白A免疫吸附治疗重症ANCA相关性血管炎肾损伤的临床效果

宋杰; 刘虹; 陈晓君; 周琳; 孙翠芳; 袁芳

doi:10.11817/j.issn.1672-7347.2023.220611

您当前的位置：

首页 >

文章列表页 >

蛋白A免疫吸附治疗重症ANCA相关性血管炎肾损伤的临床效果

扫描看全文

文章被引用时，请邮件提醒。

提交

论著 | 更新时间：2023-09-19

蛋白A免疫吸附治疗重症ANCA相关性血管炎肾损伤的临床效果
Clinical efficacy of protein A immunoadsorption therapy on severe ANCA-associated vasculitis renal injury
中南大学学报(医学版) 中南大学学报(医学版) 2023年48卷第7期页码：1026-1032
作者机构：

1.中南大学湘雅二医院肾内科，长沙 410011
2.中南大学肾脏病研究所，长沙 410011
作者简介：

宋杰，Email: 2802852611@qq.com, ORCID: 0009-0004-8466-0264
袁芳，Email: yuanfang@csu.edu.cn, ORCID: 0000-0002-5034-6603
基金信息：

湖南省临床医疗技术创新引导项目(2020SK53401)
DOI：10.11817/j.issn.1672-7347.2023.220611
中图分类号：
CSTR：
纸质出版日期： 2023-07-28 ，

收稿日期： 2022-12-05 ，

宋杰, 刘虹, 陈晓君, 周琳, 孙翠芳, 袁芳. 蛋白A免疫吸附治疗重症ANCA相关性血管炎肾损伤的临床效果[J]. 中南大学学报(医学版), 2023, 48(7): 1026-1032.

SONG Jie, LIU Hong, CHEN Xiaojun, ZHOU Lin, SUN Cuifang, YUAN Fang. Clinical efficacy of protein A immunoadsorption therapy on severe ANCA-associated vasculitis renal injury[J]. Journal of Central South University. Medical Science, 2023, 48(7): 1026-1032.
宋杰, 刘虹, 陈晓君, 周琳, 孙翠芳, 袁芳. 蛋白A免疫吸附治疗重症ANCA相关性血管炎肾损伤的临床效果[J]. 中南大学学报(医学版), 2023, 48(7): 1026-1032. DOI：10.11817/j.issn. 1672-7347.2023.220611

SONG Jie, LIU Hong, CHEN Xiaojun, ZHOU Lin, SUN Cuifang, YUAN Fang. Clinical efficacy of protein A immunoadsorption therapy on severe ANCA-associated vasculitis renal injury[J]. Journal of Central South University. Medical Science, 2023, 48(7): 1026-1032. DOI：10.11817/j.issn.1672-7347. 2023.220611

摘要

目的

抗中性粒细胞胞质抗体(anti-neutrophil cytoplasmic antibody，ANCA)相关性血管炎(ANCA-associated vasculitis，AAV)是一组累及多系统及器官的疾病，肾是最常受累的靶器官之一，部分患者短期内迅速进展至终末期肾病。既往标准诱导缓解方案治疗后仍有部分患者的缓解情况及肾脏预后较差。蛋白A免疫吸附(protein A immunoadsorption，PAIA)是一种选择性血液净化方式，在多种重症自身免疫系统疾病治疗方面表现出巨大的优势。本研究旨在探讨PAIA联合激素及免疫抑制剂在重症AAV肾损伤中的短期疗效。

方法

回顾性纳入中南大学湘雅二医院于2019至2020年间收治的10例重症AAV肾损伤患者。在诱导缓解期对患者在使用标准激素联合免疫抑制剂治疗的基础上联合PAIA治疗，于初次治疗前、PAIA治疗后、PAIA治疗后1个月及3个月时分别收集患者的人口学特征，比较治疗前后患者的免疫学指标、伯明翰血管炎活动性评分(Birmingham Vasculitis Aactivity Score，BVAS)及相关临床指标等变化，并记录其不良反应情况，评估该疗法的短期疗效。

结果

10例患者中男性6例，女性4例，年龄为(61.5±11.4)岁，从发病到确诊治疗的时长为(2.8±1.8)个月，均为抗髓过氧化物酶抗体阳性，2例合并抗蛋白酶３(anti-proteinase 3，PR3)抗体阳性(≥2.3 U/mL)。10例患者普遍表现为多器官受累，肾损伤严重，估算肾小球滤过率(estimated glomerular filtration rate，eGFR)均

30 mL/(min·1.73 m

)。随访3个月期间，10例患者BVAS、红细胞沉降率(erythrocyte sedimentation rate，ESR)及血红蛋白较治疗前的水平均可见持续改善(均

0.05)。与治疗前相比，治疗3个月后患者的ANCA滴度、血清肌酐及尿红细胞水平均下降，eGFR水平回升(均

0.05)；患者的血清白蛋白、C反应蛋白及补体水平在治疗前后的差异均无统计学意义(均

0.05)。1例患者纳入时已进入肾脏替代治疗阶段的患者治疗后未脱离维持性透析；1例患者在治疗过程中出现一过性低血压，对症处理后好转；余患者治疗过程中耐受性良好。

结论

PAIA联合激素和环磷酰胺治疗可快速降低血清ANCA水平，有效改善AAV合并肾损伤患者疾病活动情况，提示较好的短期肾脏预后，且整体安全性良好。

Abstract

Objective

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases involving multiple systems

and kidney is one of the most commonly involved target organs. Some patients may rapidly progress to end-stage renal disease in a short time. Whereas some patients have poor remission and renal prognosis after standard induction therapy. As a selective blood purification therapy

protein a immunoadsorption (PAIA) has shown great advantages on treating of severe autoimmune diseases. This study aims to evaluate the short-term efficacy of PAIA therapy combined with glucocorticoids and immunosuppressants on treating of severe AAV renal injury.

Methods

A total of 10 AAV cases with severe kidney involvement in the Second Xiangya Hospital of Central South University from 2019 to 2020 were selected for this retrospective study. During the induction remission stage

each patient was treated with PAIA on the basis of standard therapy of glucocorticoids and immunosuppressive treatment. Before and after the initial treatment

1 month and 3 months after treatment

clinical data including demographic characteristics

immunological indicators

and Birmingham Vasculitis Activity Score (BVAS) were compared. The related adverse reactions during treatment were recorded to evaluate the short-term efficacy.

Results

In this study

all 10 patients were MPO positive

and 2 patients were PR3 positive (≥2.3 U/mL). There are 6 males and 4 females at (61.5±11.4) years old

with the median time from onset to admission to hospital at (2.8±1.8) months. Multisystem damage

especially kidney damage

can be seen with eGFR lower than 30 mL/(min·1.73 m

). During the 3-month follow-up

BVAS

erythrocyte sedimentation rate

and hemoglobin of 10 patients showed continuous improvement compared with the initial admission levels (all

0.05). ANCA titer

serum creatinine and urine red blood cell were all decreased and eGFR levels were increased in 3 months after treatment (all

0.05). Serum albumin

urinary protein

C-reactive protein and complement levels showed no significant changes after treatment (all

0.05). One patient who had received renal replacement therapy was still dialysis dependent after PAIA treatment. One patient who had transient hypotension was corrected by routine treatment. The rest of the patients were all tolerant with PAIA during their treatments.

Conclusion

Treatment with PAIA combined with glucocorticoids and cyclophosphamide can rapidly lower serum ANCA level and improve disease activity in patients with AAV complicated with severe kidney damage

suggesting a good short-term renal prognosis and good overall safety.

关键词

蛋白A免疫吸附抗中性粒细胞胞质抗体相关性血管炎肾损伤疗效

Keywords

protein A immunoadsorptionanti-neutrophil cytoplasmic antibody-associated vasculitiskidney injurycurative effect

references

中华医学会肾脏病学分会专家组. 抗中性粒细胞胞质抗体相关肾炎诊断和治疗中国指南[J]. 中华肾脏病杂志, 2021, 37(7): 603-620. https://doi.org/10.3760/cma.j.cn441217-20210107- 00092https://doi.org/10.3760/cma.j.cn441217-20210107-00092.

Expert Group of the Chinese Medical Association Nephrology Section. Chinese guidelines for the diagnosis and treatment of anti-neutrophil cytoplasmic antibody-associated glomerulo-nephritis[J]. Chinese Journal of Nephrology, 2021, 37(7): 603-620. https://doi.org/10.3760/cma.j.cn441217-20210107-00092https://doi.org/10.3760/cma.j.cn441217-20210107-00092.

Schwartz J, Winters JL, Padmanabhan A, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue[J]. J Clin Apher, 2013, 28(3): 145-284. https://doi.org/10.1002/jca.21276https://doi.org/10.1002/jca.21276.

Chung SA, Langford CA, Maz M, et al. 2021 American college of rheumatology/vasculitis foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis[J]. Arthritis Rheumatol, 2021, 73(8): 1366-1383. https://doi.org/10.1002/art.41773https://doi.org/10.1002/art.41773.

Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference[J]. Arthritis Rheum, 1994, 37(2): 187-192. https://doi.org/10.1002/art.1780370206https://doi.org/10.1002/art.1780370206.

Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate[J]. Ann Intern Med, 2009, 150(9): 604-612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006https://doi.org/10.7326/0003-4819-150-9-200905050-00006.

Williams WW, Hogan JW, Ingelfinger JR. Time to eliminate health care disparities in the estimation of kidney function[J]. N Engl J Med, 2021, 385(19): 1804-1806. https://doi.org/10.1056/nejme2114918https://doi.org/10.1056/nejme2114918.

Day CJ, Howie AJ, Nightingale P, et al. Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative histomorphometric assessment and serum creatinine[J]. Am J Kidney Dis, 2010, 55(2): 250-258. https://doi.org/10.1053/j.ajkd.2009.10.047https://doi.org/10.1053/j.ajkd.2009.10.047.

Hauer HA, Bajema IM, van Houwelingen HC, et al. Determinants of outcome in ANCA-associated glomerulo-nephritis: a prospective clinico-histopathological analysis of 96 patients[J]. Kidney Int, 2002, 62(5): 1732-1742. https://doi.org/10.1046/j.1523-1755.2002.00605.xhttps://doi.org/10.1046/j.1523-1755.2002.00605.x.

Itabashi M, Takei T, Morito T, et al. Estimation of BVAS in patients with microscopic polyangiitis in Japan[J]. Clin Rheumatol, 2011, 30(11): 1499-1505. https://doi.org/10.1007/s10067-011-1838-7https://doi.org/10.1007/s10067-011-1838-7.

Hogan SL, Falk RJ, Chin H, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis[J]. Ann Intern Med, 2005, 143(9): 621-631. https://doi.org/10.7326/0003-4819-143-9-200511010-00005https://doi.org/10.7326/0003-4819-143-9-200511010-00005.

Monach PA, Warner RL, Tomasson G, et al. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis[J]. Ann Rheum Dis, 2013, 72(8): 1342-1350. https://doi.org/10.1136/annrheumdis- 2012-201981https://doi.org/10.1136/annrheumdis-2012-201981.

Draibe JB, Fulladosa X, Cruzado JM, et al. Current and novel biomarkers in anti-neutrophil cytoplasm-associated vasculitis[J]. Clin Kidney J, 2016, 9(4): 547-551. https://doi.org/10.1093/ckj/sfw056https://doi.org/10.1093/ckj/sfw056.

Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis[J]. N Engl J Med, 2020, 382(7): 622-631. https://doi.org/10.1056/NEJMoa1803537https://doi.org/10.1056/NEJMoa1803537.

Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 guideline for the management of glomerular diseases[J]. Kidney Int, 2021, 100(4): 753-779. https://doi.org/10.1016/j.kint.2021.05.015https://doi.org/10.1016/j.kint.2021.05.015.

Fuchs K, Rummler S, Ries W, et al. Performance, clinical effectiveness, and safety of immunoadsorption in a wide range of indications[J]. Ther Apher Dial, 2022, 26(1): 229-241. https:// doi.org/10.1111/1744-9987.13663https://doi.org/10.1111/1744-9987.13663.

Matic G, Bosch T, Ramlow W. Background and indications for protein A-based extracorporeal immunoadsorption[J]. Ther Apher, 2001, 5(5): 394-403. https://doi.org/10.1046/j.1526-0968.2001.00370.xhttps://doi.org/10.1046/j.1526-0968.2001.00370.x.

Braun N, Bosch T. Immunoadsorption, current status and future developments[J]. Expert Opin Investig Drugs, 2000, 9(9): 2017-2038. https://doi.org/10.1517/13543784.9.9.2017https://doi.org/10.1517/13543784.9.9.2017.

Braun N, Gutenberger S, Erley CM, et al. Immunoglobulin and circulating immune complex kinetics during immuno-adsorption onto protein A sepharose[J]. Transfus Sci, 1998, 19(Suppl): 25-31. https://doi.org/10.1016/s0955-3886(97)00099-4https://doi.org/10.1016/s0955-3886(97)00099-4.

Benny WB, Sutton DM, Oger J, et al. Clinical evaluation of a staphylococcal protein A immunoadsorption system in the treatment of myasthenia gravis patients[J]. Transfusion, 1999, 39(7): 682-687. https://doi.org/10.1046/j.1537-2995.1999. 39070682.xhttps://doi.org/10.1046/j.1537-2995.1999.39070682.x.

Moussi-Frances J, Sallée M, Jourde-Chiche N. Apheresis to treat systemic vasculitis[J]. Joint Bone Spine, 2018, 85(2): 177-183. https://doi.org/10.1016/j.jbspin.2017.06.001https://doi.org/10.1016/j.jbspin.2017.06.001.

Palmer A, Cairns T, Dische F, et al. Treatment of rapidly progressive glomerulonephritis by extracorporeal immuno-adsorption, prednisolone and cyclophosphamide[J]. Nephrol Dial Transplant, 1991, 6(8): 536-542. https://doi.org/10.1093/ndt/6.8.536https://doi.org/10.1093/ndt/6.8.536.

梅洁卉, 胡伟新, 季大玺, 等. 免疫吸附治疗ANCA相关血管炎的初步观察[J]. 肾脏病与透析肾移植杂志, 2007, 16(4): 316-321, 335. https://doi.org/10.3969/j.issn.1006-298X.2007.04.003https://doi.org/10.3969/j.issn.1006-298X.2007.04.003.

MEI Jiehui, HU Weixin, JI Daxi, et al. Effects of protein A immunoadsorption therapy in patients with ANCA-associated vasculitis and renal involvement[J]. Chinese Journal of Nephrology Dialysis & Transplantation, 2007, 16(4): 316-321, 335. https://doi.org/10.3969/j.issn.1006-298X.2007.04.003https://doi.org/10.3969/j.issn.1006-298X.2007.04.003.

浏览量

116

下载量

CSCD

工具集

关联资源

金属暴露对肾脏影响的流行病学研究进展

2019冠状病毒病相关肾损伤研究进展

内镜全层切除术在34例胃固有肌层肿瘤治疗中的应用

经口内镜下肌切开术治疗62例贲门失弛缓症患者的疗效

血友病A患儿预防治疗中凝血因子VIII剂量与疗效的相关性