儿童狼疮性肾炎分型及治疗策略

doi:10.12372/jcp.2023.23e0916

临床儿科杂志 ›› 2023, Vol. 41 ›› Issue (12): 887-894.doi: 10.12372/jcp.2023.23e0916

儿童狼疮性肾炎分型及治疗策略

高春林

东部战区总医院儿科南京大学医学院附属金陵医院（东部战区总医院）儿科南京医科大学附属金陵医院儿科南方医科大学第一临床医学院附属金陵医院儿科（江苏南京 210002）

收稿日期:2023-09-18 出版日期:2023-12-15 发布日期:2023-12-04
作者简介:高春林，女，硕士生导师，儿科学博士，博士后，长期从事儿科肾脏病临床、教学、科研工作，对儿童肾病综合征、狼疮性肾炎、紫癜性肾炎、IgA 肾病、遗尿症、遗传性肾脏病等擅长。已发表 SCI 论文 30 余篇，核心期刊论文 30 余篇；主持国家自然科学基金 1 项，参与省部级课题 2项；获教育部自然科学奖二等奖 1次，江苏省医学科技奖二等奖 1项，军队医疗成果二等奖 1次，江苏省新技术引进奖 4 项；江苏省第六期“333 高层次人才”培养对象；参编专著 6本，专利 4 项。担任中华医学会儿科学分会儿肾学组委员、江苏省医学会儿科学分会副主委、江苏省医学会儿肾学组副组长、江苏省医师协会儿科分会委员，任临床儿科杂志、中华儿科杂志、药学与临床研究杂志编委。ORCID：0000-0001-8113-311X
基金资助:
东部战区总医院临床研究专项(22LCYY-XH9)

Renal pathologic classification and treatment strategy in children with lupus nephritis

GAO Chunlin

Department of Pediatrics, Jinling Hospital; Department of Pediatrics, Jinling Hospital, Medical School of Nanjing University; Department of Pediatrics, Jinling Hospital, Nanjing Medical University; Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing 210002, Jiangsu, China

Received:2023-09-18 Published:2023-12-15 Online:2023-12-04

摘要/Abstract

摘要：

儿童狼疮性肾炎（LN）是儿童最常见的肾小球疾病，起病及病情进展均较成人严重，预后较其他肾小球疾病差，影响终生，病因未完全阐明。文章根据最新的国际指南，对儿童LN的病理分型及其相应治疗进行阐述。LN诊断根据2019年EULAR/ACR 系统性红斑狼疮分类标准，肾活检病理是目前的诊断的重要手段，增殖型和非增殖型LN治疗分为初始及维持治疗，参照成人指南推荐，合理和积极的治疗对于诱导疾病缓解和避免复发、改善预后非常重要。

关键词: 系统性红斑狼疮, 狼疮性肾炎, 治疗, 儿童

Abstract:

Lupus nephritis (LN) is the most common glomerular disease in children, with a more severe onset and progression compared to adults. The prognosis of LN in children is worse than other glomerular diseases and has lifelong effects, although the etiology remains unclear. This article provides an overview of the current diagnosis and treatment status of LN in children, along with a brief description of the treatment for each type of LN based on the latest international guidelines. LN was diagnosed according to the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus. Renal biopsy pathology is an important diagnostic method at present. Treatment for proliferative and non-proliferative LN includes initial therapy and maintenance therapy, following recommendations from adult guidelines. Rational and proactive treatment is crucial for inducing disease remission, preventing relapse, and improving prognosis.

Key words: systemic lupus erythematosus, lupus nephritis, treatment, child

高春林. 儿童狼疮性肾炎分型及治疗策略[J]. 临床儿科杂志, 2023, 41(12): 887-894.

GAO Chunlin. Renal pathologic classification and treatment strategy in children with lupus nephritis[J]. Journal of Clinical Pediatrics, 2023, 41(12): 887-894.

图/表 1

参考文献 42

[1]	Kamphuis S, Silverman ED. Prevalence and burden of pediatric-onset systemic lupus erythematosus[J]. Nat Rev Rheumatol, 2010, 6(9): 538-546. doi: 10.1038/nrrheum.2010.121 pmid: 20683438
[2]	Feldman CH, Broder A, Guan H, et al. Sex differences in health care utilization, end-stage renal disease, and mortality among medicaid beneficiaries with incident lupus nephritis[J]. Arthritis Rheumatol, 2018, 70(3): 417-426. doi: 10.1002/art.v70.3
[3]	Fujikawa S, Okuni M. A nationwide surveillance study of rheumatic diseases among Japanese children[J]. Acta Paediatr Jpn, 1997, 39: 242-244. doi: 10.1111/ped.1997.39.issue-2
[4]	Tsioni V, Andreoli L, Meini A, et al. The prevalence and incidence of systemic lupus erythematosus in children and adults: a population-based study in a mountain community in northern Italy[J]. Clin Exp Rheumatol, 2015, 33(5): 681-687. pmid: 26089119
[5]	Ambrose N, Morgan TA, Galloway J, et al. Differences in disease phenotype and severity in SLE across age groups[J]. Lupus, 2016, 25(14): 1542-1550. pmid: 27147622
[6]	Massias JS, Smith EMD, Al-Abadi E, et al. Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups[J]. Lupus, 2020, 29(5): 474-481. doi: 10.1177/0961203320909156 pmid: 32233733
[7]	Hiraki LT, Feldman CH, Liu J, et al. Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US medicaid beneficiary population[J]. Arthritis Rheum, 2012, 64: 2669-2676. doi: 10.1002/art.v64.8
[8]	Massias JS, Smith EM, Al-Abadi E, et al. Clinical and laboratory phenotypes in juvenile-onset systemic lupus erythematosus across ethnicities in the UK[J]. Lupus, 2021, 30(4): 597-607. doi: 10.1177/0961203320984251 pmid: 33413005
[9]	Sassi RH, Hendler JV, Piccoli GF, et al. Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus[J]. Clin Rheumatol, 2017, 36(1): 89-95. doi: 10.1007/s10067-016-3478-4 pmid: 27858177
[10]	Wang SF, Chen YH, Chen DQ, et al. Mesangial proliferative lupus nephritis with podocytopathy: a special entity of lupus nephritis[J]. Lupus, 2018, 27(2): 303-311. doi: 10.1177/0961203317720526 pmid: 28720048
[11]	Oni L, Wright RD, Marks S, et al. Kidney outcomes for children with lupus nephritis[J]. Pediatr Nephrol, 2021, 36: 1377-1385. doi: 10.1007/s00467-020-04686-1
[12]	Houssiau FA, Vasconcelos C, D'Cruz D, et al. Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: lessons from long-term followup of patients in the Euro-Lupus Nephritis Trial[J]. Arthritis Rheum, 2004, 50(12): 3934-3940. doi: 10.1002/art.v50:12
[13]	Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis[J]. Nat Rev Dis Primers, 2020, 6(1): 7. doi: 10.1038/s41572-019-0141-9
[14]	Lu R, Robertson JM, Bruner BF, et al. Multiple autoantibodies display association with lymphopenia, proteinuria, and cellular casts in a large, ethnically diverse SLE patient cohort[J]. Autoimmune Dis, 2012: 819634
[15]	Santacruz JC, Mantilla MJ, Rueda I, et al. A practical perspective of the hematologic manifestations of systemic lupus erythematosus[J]. Cureus, 2022, 14(3): e22938.
[16]	Fayyaz A, Igoe A, Kurien BT, et al. Haematological manifestations of lupus[J]. Lupus Sci Med, 2015, 2(1): e000078. doi: 10.1136/lupus-2014-000078
[17]	Kocheril AP, Vettiyil GI, George AS, et al. Pediatric systemic lupus erythematosus with lupus anticoagulant hypoprothrombinemia syndrome-a case series with review of literature[J]. Lupus, 2021, 30(4): 641-648. doi: 10.1177/0961203321988934 pmid: 33509039
[18]	Suyama Y, Okada M, Rokutanda R, et al. Safety and efficacy of upfront graded administration of trimethoprim-sulfamethoxazole in systemic lupus erythematosus: a retrospective cohort study[J]. Mod Rheumatol, 2016, 26(4): 557-561. doi: 10.3109/14397595.2015.1112467 pmid: 26587755
[19]	Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis[J]. Ann Rheum Dis, 2020, 79(6): 713-723. doi: 10.1136/annrheumdis-2020-216924 pmid: 32220834
[20]	Kidney Disease: Improving Global Outcomes KDIGO Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular Diseases[J]. Kidney Int, 2021, 100(4S): S1-S276. doi: 10.1016/j.kint.2021.05.021 pmid: 34556256
[21]	Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus[J]. Ann Rheum Dis, 2019, 78(9): 1151-1159. doi: 10.1136/annrheumdis-2018-214819 pmid: 31383717
[22]	中华医学会儿科分会肾脏学组. 儿童狼疮性肾炎诊治循证指南(2016)[J]. 中华儿科杂志, 2018, 56(2): 88-94.
[23]	Wakiguchi H, Takei S, Kubota T, et al. Treatable renal disease in children with silent lupus nephritis detected by baseline biopsy: association with serum C3 levels[J]. Clin Rheumatol, 2017, 36(2): 433-437. doi: 10.1007/s10067-016-3491-7 pmid: 27900491
[24]	Narváez J, Ricse M, Gomà M, et al. The value of repeat biopsy in lupus nephritis flares[J]. Medicine (Baltimore), 2017, 96(24): e7099. doi: 10.1097/MD.0000000000007099
[25]	Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited[J]. Kidney Int, 2004, 65(2): 521-530. doi: 10.1111/j.1523-1755.2004.00443.x pmid: 14717922
[26]	Bajema IM, Wilhelmus S, Alpers CE, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices[J]. Kidney Int, 2018, 93(4): 789-796. doi: S0085-2538(17)30859-1 pmid: 29459092
[27]	Hu W, Chen Y, Wang S, et al. Clinical-morphological features and outcomes of lupus podocytopathy[J]. Clin J Am Soc Nephrol, 2016, 11(4): 585-592. doi: 10.2215/CJN.06720615
[28]	Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis[J]. Nat Rev Nephrol, 2011, 7(12): 718-729. doi: 10.1038/nrneph.2011.150
[29]	Yusuf IH, Charbel Issa P, Ahn SJ. Hydroxychloroquine-induced retinal toxicity[J]. Front Pharmacol, 2023, 14: 1196783. doi: 10.3389/fphar.2023.1196783
[30]	Anders HJ, Loutan J, Bruchfeld A, et al. The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 2021[J]. Nephrol Dial Transplant, 2023, 38(3): 551-561. doi: 10.1093/ndt/gfab351
[31]	Houssiau FA, Vasconcelos C, D'Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide[J]. Ann Rheum Dis, 2010, 69(1): 61-64. doi: 10.1136/ard.2008.102533 pmid: 19155235
[32]	Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis[J]. J Am Soc Nephrol, 2009, 20: 1103-1112. doi: 10.1681/ASN.2008101028 pmid: 19369404
[33]	Yang TH, Wu TH, Chang YL, et al. Cyclosporine for the treatment of lupus nephritis in patients with systemic lupus erythematosus[J]. Clin Nephrol, 2018, 89: 277-285. doi: 10.5414/CN109325
[34]	Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis[J]. N Engl J Med, 2005, 353: 2219-2228. doi: 10.1056/NEJMoa043731
[35]	Chan TM, Tse KC, Tang CS, et al. Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine[J]. Lupus, 2005, 14: 265-272. doi: 10.1191/0961203305lu2081oa pmid: 15864912
[36]	Zhang M, Qi C, Zha Y, et al. Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial[J]. Clin Rheumatol, 2019, 38: 859-867. doi: 10.1007/s10067-018-4348-z pmid: 30426311
[37]	Furie R, Rovin BH, Houssiau F, et al. Safety and efficacy of belimumab in patients with lupus nephritis open-label extension of BLISS-LN study[J]. Clin J Am Soc Nephrol, 2022, 17: 1620-1630. doi: 10.2215/CJN.02520322
[38]	Austin HA, 3rd, Illei GG, Braun MJ, et al. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy[J]. J Am Soc Nephrol, 2009, 20: 901-911. doi: 10.1681/ASN.2008060665 pmid: 19297556
[39]	Wasik H, Chadha V, Galbiati S, et al. Dialysis outcomes for children with lupus nephritis compared to children with other forms of nephritis: a retrospective cohort study[J]. Am J Kidney Dis, 2022, 79(5): 626-634. doi: 10.1053/j.ajkd.2021.07.013
[40]	Mai K, Singer P, Fahmy AE, et al. Kidney transplant outcomes in children and adolescents with systemic lupus erythematosus[J]. Pediatr Transplant, 2022, 26(1): e14178. doi: 10.1111/petr.v26.1
[41]	Gipson DS, Ferris ME, Dooley MA, et al. Renal transplantation in children with lupus nephritis[J]. Am J Kidney Dis, 2003, 41(2): 455-463. pmid: 12552510
[42]	Rangoonwala S, Marks SD. Kidney transplantation outcomes for children and young people with lupus nephritis[J]. Pediatr Transplant, 2022, 26(1): e14193. doi: 10.1111/petr.v26.1

治疗	方案	LN Ⅰ、Ⅱ型	LN Ⅲ、Ⅳ（±Ⅴ）型	LN Ⅴ型
初始治疗	常用方案	①非肾病范围蛋白尿：肾外表现来决定免疫抑制剂 ②肾病范围蛋白尿：GC ③镜下血尿：不需要针对肾病治疗 ④足细胞病：GC	①GC+MPAA ②GC+CTX ③GC+贝利尤单抗+MPAA或低剂量CTX ④GC+MPAA+CNIs	①非肾病范围蛋白尿：肾外表现来决定免疫抑制剂 ②肾病范围蛋白尿：GC+MPAA或GC+CTX（<6个月）或GC+CNIs或GC+利妥昔单抗（RTX）或GC+AZA
初始治疗	替代方案		GC+AZA GC+来氟米特
维持治疗		MPAA/AZA/贝利尤单抗
基础治疗	羟氯喹

儿童狼疮性肾炎分型及治疗策略

Renal pathologic classification and treatment strategy in children with lupus nephritis

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

图/表 1

参考文献 42

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	林锦凤, 陈伊, 邓燕, 冯爱, 黄隽, 陈丽珠, 谢靖麒, 聂晓晶. 化学发光法与细胞间接免疫荧光法检测儿童肾病综合征血清抗Nephrin抗体的比较研究[J]. 临床儿科杂志, 2026, 44(8): 682-689.
[2]	郑方圆, 王淼, 丁明明, 陆爱东, 贾月萍, 曾慧敏, 张乐萍. 儿童费城染色体阳性急性淋巴细胞白血病二代测序基因变异及预后意义的回顾性队列研究[J]. 临床儿科杂志, 2026, 44(8): 690-697.
[3]	张晓, 方红军, 旷小军, 王丽娟, 吴照, 蒋莎, 李佩, 吴丽文. 儿童失张力发作的临床与电生理特征分析[J]. 临床儿科杂志, 2026, 44(8): 698-704.
[4]	王梦倩, 杨辉. 儿童肠型贝赫切特综合征13例病例系列分析[J]. 临床儿科杂志, 2026, 44(8): 705-711.
[5]	吴喜蓉, 高琦, 郭思远, 尹青琴, 秦强, 殷菊, 焦安夏, 陈诚豪, 吴迪, 王蓓, 段晓岷, 彭芸, 徐保平, 高立伟. 儿童糖尿病合并肺毛霉病患者临床特征及预后分析[J]. 临床儿科杂志, 2026, 44(8): 712-720.
[6]	韩亚男, 葛兰兰, 崔洁媛. 1例EYA1基因变异所致鳃-耳-肾综合征患儿的6年诊治及随访报告[J]. 临床儿科杂志, 2026, 44(8): 721-726.
[7]	时嘉仪, 高春林, 贾丽丽, 陆云云, 孙涛, 朱小东, 夏正坤, 张沛. COQ2基因复合杂合突变致儿童孤立性肾病综合征1家系表型特征与预后分析[J]. 临床儿科杂志, 2026, 44(8): 727-732.
[8]	林罗娜, 刘娟娟, 王红玉, 胡波飞, 徐翼, 黄丽素. 儿童流感肺外综合征的发病机制、临床特征与防治：从异位感染到免疫介导损伤[J]. 临床儿科杂志, 2026, 44(8): 733-739.
[9]	贾世辰, 徐国锋. 胱氨酸尿症的诊治进展[J]. 临床儿科杂志, 2026, 44(8): 740-746.
[10]	程于恒, 徐子朝, 陈颖. X-连锁低磷性佝偻病诊疗新进展[J]. 临床儿科杂志, 2026, 44(8): 747-754.
[11]	Rachel Rosen, Osvaldo Borrelli, Christophe Faure, Katja Karrento, Usha Krishnan, Samuel Nurko, Nathalie Rommel, Alan Silverman, Michiel van Wijk, Marc Benninga (著), 中华医学会肠外肠内营养学分会儿科学组, 中华医学会儿科学分会消化学组, 中国医师协会儿科医师分会消化学组（译）. 罗马Ⅴ诊断标准核心释义与解读：肠-脑互动异常的儿童与青少年上消化道疾病[J]. 临床儿科杂志, 2026, 44(7): 595-608.
[12]	Carlo Di Lorenzo, Miguel Saps, Bruno P. Chumpitazi, Shaman Rajindrajith, Annamaria Staiano, Nikhil Thapar, Miranda van Tilburg, Carlos Velasco-Benítez, Arine Vlieger（著）, 中华医学会肠外肠内营养学分会儿科学组, 中华医学会儿科学分会消化学组, 中国医师协会儿科医师分会消化学组（译）. 罗马Ⅴ诊断标准核心释义与解读：肠-脑互动异常的儿童与青少年下消化道及胆道疾病[J]. 临床儿科杂志, 2026, 44(7): 609-621.
[13]	李旭峰, 唐浩勋, 李兴军, 张立泽, 高晨晴, 赵顺英, 刘建华. 儿童肺炎衣原体肺炎76例临床特点及影像学分型与预后相关性分析[J]. 临床儿科杂志, 2026, 44(7): 622-627.
[14]	王真, 邵静波, 张娜, 夏敏, 朱嘉莳, 杜成坎, 李红. 初诊低危组儿童急性淋巴细胞白血病远期复发影响因素：基于单中心254例患儿的5年随访分析[J]. 临床儿科杂志, 2026, 44(7): 628-635.
[15]	郭雪梅, 薛瑶, 王永韧, 戎留成, 方拥军, 林如峰. 伴CBFA2T3::GLIS2融合基因的儿童急性髓系白血病临床特征及预后分析[J]. 临床儿科杂志, 2026, 44(7): 636-643.