风湿免疫性疾病肾脏受累的临床表现

doi:10.16138/j.1673-6087.2025.05.12

摘要/Abstract

摘要：

风湿免疫性疾病常累及多系统、多器官，肾脏是常见的受累器官。不同风湿病引起的肾脏临床表现多样，轻重不一，可表现为无症状性血尿、蛋白尿，也可进展为急进性肾炎甚至肾功能衰竭等。不同临床表现对应的治疗策略和预后不同。本文通过回顾国内外相关文献，总结常见风湿免疫性疾病肾脏受累的临床和病理表现，旨在提高临床医师对这类疾病的认识，及早采取相应措施，改善患者预后。

关键词: 风湿免疫性疾病, 肾小管间质性肾炎, 肾小球肾炎, 流行病学

Abstract:

Rheumatic autoimmune diseases are characterized by the involvement of multiple systems and organs, and the kidney is a common and critical target. The clinical manifestations of kidney diseases caused by different rheumatic diseases are diverse, ranging from asymptomatic hematuria and proteinuria to rapidly progressive glomerulonephritis and renal failure, and vary in severity. The treatment strategies and prognosis differ depending on the specific clinical manifestation. This article reviews relevant domestic and international literature, summarizing the renal manifestations associated with common rheumatic diseases. The aim is to improve clinicians’ understanding of the diseases, enabling them to intervene early to improve patient outcomes.

Key words: Rheumatic autoimmune diseases, Tubulointerstitial nephritis, Glomerulonephritis, Epidemiology

中图分类号:

R593.2

张小艳, 李慧凛. 风湿免疫性疾病肾脏受累的临床表现[J]. 内科理论与实践, 2025, 20(05): 410-414.

ZHANG Xiaoyan, LI Huilin. Renal manifestations of rheumatic autoimmune diseases[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(05): 410-414.

图/表 2

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参考文献 37

[1]	Hanly JG, O’Keeffe AG, Su L, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study[J]. Rheumatology (Oxford), 2016, 55(2): 252-262. doi: 10.1093/rheumatology/kev311
[2]	Mohan C, Zhang T, Putterman C. Pathogenic cellular and molecular mediators in lupus nephritis[J]. Nat Rev Nephrol, 2023, 19(8): 491-508. doi: 10.1038/s41581-023-00722-z
[3]	Parodis I, Rovin BH, Tektonidou MG, et al. Lupus nephritis[J]. Nat Rev Dis Primers, 2025, 11(1): 69. doi: 10.1038/s41572-025-00653-y
[4]	Mahajan A, Amelio J, Gairy K, et al. Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression[J]. Lupus, 2020, 29(9): 1011-1020. doi: 10.1177/0961203320932219
[5]	Gisca E, Duarte L, Farinha F, et al. Assessing outcomes in a lupus nephritis cohort over a 40-year period[J]. Rheumatology (Oxford), 2021, 60(4): 1814-1822. doi: 10.1093/rheumatology/keaa491
[6]	Saxena R. Predicting kidney survival in lupus nephritis by adding clinical data to pathologic features[J]. Kidney360, 2022, 3(1): 5-7. doi: 10.34067/KID.0007082021
[7]	Gasparotto M, Gatto M, Binda V, et al. Lupus nephritis: clinical presentations and outcomes in the 21st century[J]. Rheumatology (Oxford), 2020, 59(Suppl 5): v39-v51.
[8]	Vazzana KM, Daga A, Goilav B, et al. Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort[J]. Lupus, 2021, 30(10): 1660-1670.
[9]	Yap DYH, Xu X, Juliao PC, et al. Long-term kidney outcome of lupus nephritis by renal response status[J]. Kidney Int Rep, 2024, 9(12): 3532-3541. doi: 10.1016/j.ekir.2024.09.028
[10]	Parikh SV, Almaani S, Brodsky S, et al. Update on lupus nephritis: Core Curriculum 2020[J]. Am J Kidney Dis, 2020, 76(2): 265-281. doi: 10.1053/j.ajkd.2019.10.017
[11]	Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update[J]. Ann Rheum Dis, 2024, 83(1): 15-29. doi: 10.1136/ard-2023-224762
[12]	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.
[13]	Anders HJ, Saxena R, Zhao MH, et al. Lupus nephritis[J]. Nat Rev Dis Primers, 2020, 6(1): 7.
[14]	Parodis I, Adamichou C, Aydin S, et al. Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis[J]. Rheumatology (Oxford), 2020, 59(11): 3424-3434. doi: 10.1093/rheumatology/keaa129
[15]	Louis Sam Titus ASC, Tan Y, Tran P, et al. Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics[J]. Clin Immunol, 2023, 254: 109713. doi: 10.1016/j.clim.2023.109713
[16]	Paul M, Addya S, Sengupta M, et al. Spectrum of renal vascular lesions among patients with lupus nephritis: an experience from a tertiary care center[J]. Indian J Pathol Microbiol, 2023, 66(4): 751-757. doi: 10.4103/ijpm.ijpm_327_22
[17]	Xia W, Deng J, Zhuang L, et al. Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy[J]. Clin Kidney J, 2024, 17(6): sfae148. doi: 10.1093/ckj/sfae148
[18]	Jasiek M, Karras A, Le Guern V, et al. A multicentre study of 95 biopsy-proven cases of renal disease in primary Sjögren's syndrome [J]. Rheumatology (Oxford), 2017, 56(3): 362-370.
[19]	Yang HX, Wang J, Wen YB, et al. Renal involvement in primary Sjögren's syndrome: A retrospective study of 103 biopsy-proven cases from a single center in China[J]. Int J Rheum Dis, 2018, 21(1): 223-229. doi: 10.1111/1756-185X.13182
[20]	Chatterjee R, Balakrishnan A, Kharbanda R, et al. Renal involvement in Sjőgren's syndrome: predictors and impact on patient outcomes[J]. Rheumatol Int, 2023, 43(7): 1297-1306. doi: 10.1007/s00296-022-05242-w
[21]	Aiyegbusi O, McGregor L, McGeoch L, et al. Renal disease in primary Sjogren’s syndrome[J]. Rheumatol Ther, 2021, 8(1): 63-80. doi: 10.1007/s40744-020-00264-x
[22]	Maleki-Fischbach M, Kastsianok L, Koslow M, et al. Manifestations and management of Sjogren's disease[J]. Arthritis Res Ther, 2024, 26(1): 43. doi: 10.1186/s13075-024-03262-4
[23]	Brito-Zerón P, Acar-Denizli N, Ng WF, et al. Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome[J]. Rheumatology (Oxford), 2020, 59(9): 2350-2359. doi: 10.1093/rheumatology/kez578
[24]	Trevisani VFM, Pugliesi A, Pasoto SG, et al. Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal)[J]. Adv Rheumatol, 2022, 62(1): 18. doi: 10.1186/s42358-022-00248-1
[25]	Luo J, Xu S, Lv Y, et al. Clinical features and potential relevant factors of renal involvement in primary Sjogren’s syndrome[J]. Int J Rheum Dis, 2019, 22(2): 182-190. doi: 10.1111/1756-185X.13429
[26]	Baldini C, Fulvio G, La Rocca G, et al. Update on the pathophysiology and treatment of primary Sjogren syndrome[J]. Nat Rev Rheumatol, 2024, 20(8): 473-491. doi: 10.1038/s41584-024-01135-3
[27]	Goules A, Geetha D, Arend LJ , et al. Renal involvement in primary Sjögren’s syndrome:natural history and treatment outcome [J]. Clin Exp Rheumatol, 2019, 37 Suppl 118(3):123-132.
[28]	Hanberg JS, Cook C, Fu X, et al. Longitudinal patterns of renal function in antineutrophil cytoplasmic antibody-associated vasculitis[J]. Arthritis Care Res (Hoboken), 2023, 75(10): 2190-2198. doi: 10.1002/acr.25100
[29]	Guo Q, Yu L, Zhang X, et al. Analysis of the risk factors for end-stage renal disease and mortality in ANCA-associated vasculitis: a study from a single center of the Chinese Rheumatism Data Center[J]. Clin Rheumatol, 2023, 42(2): 489-499. doi: 10.1007/s10067-022-06419-1
[30]	Trivioli G, Gopaluni S, Urban ML, et al. Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome[J]. Clin Kidney J, 2020, 14(1): 332-340.
[31]	Christodoulou M, Moysidou E, Lioulios G, et al. The prognostic value of two histopathologic classification models of ANCA-associated glomerulonephritis: a prospective study[J]. J Nephrol, 2024, 37(4): 941-950. doi: 10.1007/s40620-023-01855-x
[32]	Boud'hors C, Copin MC, Wacrenier S, et al. Histopathological prognostic factors in ANCA-associated glomerulonephritis[J]. Autoimmun Rev, 2022, 21(9): 103139. doi: 10.1016/j.autrev.2022.103139
[33]	Hudson M, Ghossein C, Steen V. Scleroderma renal crisis[J]. Presse Med, 2021, 50(1): 104063. doi: 10.1016/j.lpm.2021.104063
[34]	莫颖倩, 严青, 叶霜, 等. 未分化结缔组织病和混合性结缔组织病的诊疗规范[J]. 中华内科杂志, 2022, 61(10): 1119-1127. doi: 10.3760/cma.j.cn112138-20220104-00009
	Mo YQ, Yan Q, Ye S, et al. Standardized diagnosis and treatment of undifferentiated connective tissue disease and mixed connective tissue disease[J]. Chin J Intern Med, 2022, 61(10): 1119-1127. doi: 10.3760/cma.j.cn112138-20220104-00009
[35]	Madieh J, Khamayseh I, Hrizat A, et al. Scleroderma renal crisis in a case of mixed connective tissue disease treated successfully with angiotensin-converting enzyme inhibitors [J]. Case Rep Nephrol, 2021, 2021: 8862405.
[36]	Kawano M, Saeki T, Ubara Y, et al. Recent advances in IgG4-related kidney disease [J]. Mod Rheumatol, 2023, 33(2): 242-251.
[37]	黄烽, 朱剑, 王玉华, 等. 强直性脊柱炎诊疗规范[J]. 中华内科杂志, 2022, 61(8): 893-900.
	Huang F, Zhu J. Wang YH, et al. Recommendations for diagnosis and treatment of ankylosing spondylitis [J]. Chin J Intern Med, 2022, 61(8): 893-900.

疾病类型	肾受累率	临床表现	病理表现	ANCA阳性
MPO：髓过氧化物酶（myeloperoxidase）；p-ANCA:核周型ANCA（perinuclear ANCA）；PR3-ANCA: 蛋白酶3ANCA（proteinase 3 ANCA）
MPA	80%	急进性肾小球肾炎、无症状性血尿、不同程度蛋白尿及肾功能不全	寡免疫复合物沉积、轻度局灶节段性肾小球肾炎、弥漫坏死性新月体性肾小球肾炎、间质性肾炎	60%~80%，主要为MPO-ANCA及p-ANCA阳性
GPA	60%~80%	急进性肾小球肾炎、无症状性血尿、不同程度蛋白尿及肾功能不全	寡免疫复合物沉积、轻度局灶节段性肾小球肾炎、弥漫坏死性新月体性肾小球肾炎，偶见肉芽肿	70%~90%为PR3-ANCA阳性，少数为MPO-ANCA阳性
EGPA	20%	急进性肾小球肾炎、无症状性血尿、不同程度蛋白尿及肾功能不全	坏死性新月体性肾小球肾炎、嗜酸性粒细胞性间质性肾炎、膜性肾小球肾炎、局灶节段性肾小球硬化	1/3患者ANCA阳性，多为p-ANCA
大动脉炎	78.1%	高血压、蛋白尿、肾功能不全、ESKD	肾动脉狭窄	/
结节性多动脉炎	不详	急进性肾衰竭，镜下血尿甚至肉眼血尿、细胞管型、蛋白尿、肾性高血压、肾病综合征	缺血性肾病、肾微动脉瘤、输尿管周围组织血管炎及继发纤维化	/

	肾受累率	临床表现	病理表现	鉴别诊断
SSc	35%~40%^[33]	50%的SSc患者表现为轻度蛋白尿、血肌酐升高和(或)高血压, 6%发生硬皮病肾危象^[33]	血管腔狭窄堵塞的内膜增殖和增厚，伴向心性“葱皮样”肥大、血栓性微血管病	其他原因所致的肾功能不全、硬皮病肾危象需要与其他血栓性微血管病相鉴别
MCTD	25%^[34]	肾小球肾炎、肾病综合征、肾小管酸中毒、肾脏浓缩功能受损、肾结石或间质性肾炎^[35]，少数可发生肾危象	膜性肾病、TIN、系膜增生性肾小球肾炎	原发性膜性肾病、其他原因引起的肾小管及肾间质炎
IgG4-RD	7.0%~24.6%^[36]	肾功能不全、尿检异常、尿路梗阻、肾盂占位	TIN、膜性肾病	药物性间质性肾炎、慢性肾盂肾炎、多中心型淋巴结增生症、其他自身免疫性疾病相关间质性肾炎
AS	10%~35%^[37]	尿检异常	非特异性肾小球病、IgA肾病、淀粉样变性	与原发性肾小球病较难鉴别，需从临床表现、全面体检、辅助检查等鉴别
RA	很少直接导致	尿检异常	系膜增生性或膜性肾小球肾炎、淀粉样变性	与原发性肾小球病及药物引起的肾损伤相鉴别，控制RA可改善淀粉样变