原发性膜性肾病生物标志物的研究进展
Research Progress on Biomarkers of Primary Membranous Nephropathy
摘要: 原发性膜性肾病(membranous nephropathy, PMN)是一种自身免疫性疾病。其临床表现多样，疾病进程不一，部分患者可自发缓解，而部分进展至肾衰竭。传统的诊断依赖于肾活检病理，但肾活检具有侵入性，且难以实时动态监测病情变化。生物标志物的探寻为PMN的诊疗开辟了新途径，能辅助早期无创诊断、预测疾病转归，优化个体化治疗策略。本文综合阐述了近年来PMN相关的各类生物标志物，分析其研究现状、临床应用价值及局限性，旨在为临床实践与进一步研究提供全面参考，推动PMN精准医疗的发展。
Abstract: Primary membranous nephropathy (PMN) is an autoimmune disease. Its clinical manifestations are diverse, and the disease course varies, with some patients resolving spontaneously and some progressing to renal failure. Traditional diagnosis relies on kidney biopsy pathology, but kidney biopsy is invasive and difficult to dynamically monitor changes in real time. The exploration of biomarkers has opened up new avenues for the diagnosis and treatment of PMN, which can assist in early non-invasive diagnosis, predict disease outcome, and optimize individualized treatment strategies. This paper comprehensively describes various biomarkers related to PMN in recent years, analyzes their research status, clinical application value and limitations, aiming to provide a comprehensive reference for clinical practice and further research, and promote the development of PMN precision medicine.
文章引用：袁满, 魏明明. 原发性膜性肾病生物标志物的研究进展[J]. 临床个性化医学, 2026, 5(2): 154-160. https://doi.org/10.12677/jcpm.2026.52113

参考文献

[1] 张传磊, 高刘传, 徐莹莹. 尿CXCL10、CXCL16在特发性膜性肾病患者中的表达及临床意义[J]. 现代生物医学进展, 2025, 25(16): 2689-2697.
[2] 李文丽, 王蔚. 原发性膜性肾病的遗传学研究进展[J]. 实用医院临床杂志, 2025, 22(3): 189-192.
[3] Couser, W.G. (2017) Primary Membranous Nephropathy. Clinical Journal of the American Society of Nephrology, 12, 983-997. [Google Scholar] [CrossRef] [PubMed]
[4] Wang, X., Song, X., Sun, N. and Chang, W. (2025) Efficacy and Safety of Ripertamab for Treating Primary Membranous Nephropathy among Adults: A Multicenter, Retrospective, Real-World Study. Frontiers in Immunology, 16, Article ID: 1540694. [Google Scholar] [CrossRef] [PubMed]
[5] 张富玥, 严瑞. 原发性膜性肾病治疗的研究进展[J]. 重庆医学, 2025, 54(8): 1930-1935.
[6] 胡晓帆, 徐静. 原发性膜性肾病诊治的新进展[J]. 诊断学理论与实践, 2025, 24(3): 249-254.
[7] Murtas, C., Bruschi, M., Spinelli, S., Kajana, X., Verrina, E.E., Angeletti, A., et al. (2023) Novel Biomarkers and Pathophysiology of Membranous Nephropathy: PLA2R and Beyond. Clinical Kidney Journal, 17, sfad228. [Google Scholar] [CrossRef] [PubMed]
[8] 郭晓琴, 于为民, 任小军. 膜性肾病诊断和治疗的研究进展[J]. 实用医学杂志, 2021, 37(12): 1636-1640.
[9] 袁文明, 程根阳, 李炎生, 等. PLA2R和IgG4对老年原发性膜性肾病的诊断价值[J]. 解放军医学杂志, 2017, 42(9): 810-814.
[10] 邵丹丹, 何伟春. 原发性膜性肾病自身抗原的研究进展[J]. 中国医药, 2024, 19(5): 787-792.
[11] 钟兰星, 梁新华. 血清PLA2R抗体与原发性膜性肾病临床病理的关系[J]. 海南医学, 2025, 36(2): 176-180.
[12] Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group (2021) KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International, 100, S1-S276.
[13] Passerini, P., Malvica, S., Tripodi, F., Cerutti, R. and Messa, P. (2019) Membranous Nephropathy (MN) Recurrence after Renal Transplantation. Frontiers in Immunology, 10, Article No. 1326. [Google Scholar] [CrossRef] [PubMed]
[14] Ragy, O., Abass, W., Kanigicherla, D.A.K., Shinkins, B., Bestall, J., King, N., et al. (2025) PLA2R Autoantibodies, a Multifaceted Biomarker in Nephrotic Syndrome and Membranous Nephropathy. Nephrology Dialysis Transplantation, 40, 1458-1469. [Google Scholar] [CrossRef] [PubMed]
[15] 李佳, 邓榕, 黄清水. 膜性肾病相关自身抗体检测的临床意义[J]. 中华检验医学杂志, 2024, 47(9): 993-998.
[16] 李珺, 王艳艳, 程虹. Ⅰ型血小板反应蛋白7A域及其抗体在特发性膜性肾病中的研究进展[J]. 临床肾脏病杂志, 2019, 19(8): 624-627.
[17] Liu, Y., Zheng, S., Ma, C., Lian, Y., Zheng, X., Guan, P., et al. (2020) Meta‐Analysis of the Diagnostic Efficiency of THSD7A‐AB for the Diagnosis of Idiopathic Membranous Nephropathy. Global Challenges, 4, Article ID: 1900099. [Google Scholar] [CrossRef] [PubMed]
[18] Zaghrini, C., Seitz-Polski, B., Justino, J., Dolla, G., Payré, C., Jourde-Chiche, N., et al. (2019) Novel ELISA for Thrombospondin Type 1 Domain-Containing 7A Autoantibodies in Membranous Nephropathy. Kidney International, 95, 666-679. [Google Scholar] [CrossRef] [PubMed]
[19] 彭珊, 刘维萍. Nel样1型分子基因的研究现状及最新进展[J]. 中华肾病研究电子杂志, 2020, 9(6): 272-274.
[20] Hasebe, A., Tashima, H., Ide, T., Iijima, M., Yoshimoto, N., Ting, K., et al. (2011) Efficient Production and Characterization of Recombinant Human NELL1 Protein in Human Embryonic Kidney 293-F Cells. Molecular Biotechnology, 51, 58-66. [Google Scholar] [CrossRef] [PubMed]
[21] Wang, G., Sun, L., Dong, H., Wang, Y., Xu, X., Zhao, Z., et al. (2021) Neural Epidermal Growth Factor-Like 1 Protein-Positive Membranous Nephropathy in Chinese Patients. Clinical Journal of the American Society of Nephrology, 16, 727-735. [Google Scholar] [CrossRef] [PubMed]
[22] Sethi, S., Debiec, H., Madden, B., Charlesworth, M.C., Morelle, J., Gross, L., et al. (2020) Neural Epidermal Growth Factor-Like 1 Protein (NELL-1) Associated Membranous Nephropathy. Kidney International, 97, 163-174. [Google Scholar] [CrossRef] [PubMed]
[23] Caza, T.N., Hassen, S.I., Dvanajscak, Z., Kuperman, M., Edmondson, R., Herzog, C., et al. (2021) NELL1 Is a Target Antigen in Malignancy-Associated Membranous Nephropathy. Kidney International, 99, 967-976. [Google Scholar] [CrossRef] [PubMed]
[24] Sethi, S., Debiec, H., Madden, B., Vivarelli, M., Charlesworth, M.C., Ravindran, A., et al. (2020) Semaphorin 3b-Associated Membranous Nephropathy Is a Distinct Type of Disease Predominantly Present in Pediatric Patients. Kidney International, 98, 1253-1264. [Google Scholar] [CrossRef] [PubMed]
[25] Huang, G., Liu, F., Yu, L., Wang, J., Chen, J. and Mao, J. (2022) Pediatric Membranous Nephropathy: In the Novel Antigens Era. Frontiers in Immunology, 13, Article ID: 962502. [Google Scholar] [CrossRef] [PubMed]
[26] Fila, M., Debiec, H., Perrochia, H., Djouadi, N., Verpont, M., Buob, D., et al. (2022) Recurrence of Anti-Semaphorin 3B-Mediated Membranous Nephropathy after Kidney Transplantation. Journal of the American Society of Nephrology, 33, 503-509. [Google Scholar] [CrossRef] [PubMed]
[27] Wang, C., Chen, A., Ruan, B., Niu, Z., Su, Y., Qin, H., et al. (2020) PCDH7 Inhibits the Formation of Homotypic Cell-In-Cell Structure. Frontiers in Cell and Developmental Biology, 8, Article No. 329. [Google Scholar] [CrossRef] [PubMed]
[28] Sethi, S., Madden, B., Debiec, H., Morelle, J., Charlesworth, M.C., Gross, L., et al. (2021) Protocadherin 7-Associated Membranous Nephropathy. Journal of the American Society of Nephrology, 32, 1249-1261. [Google Scholar] [CrossRef] [PubMed]
[29] Machalitza, M., Debiec, H., Krümpelmann, B., Ferru, N., Kilictas, M.E., Huber, T.B., et al. (2025) PCDH7-Antibodies and PCDH7 Immune Deposits Are Mostly Found in Patients with PLA2R1-or NELL1-Associated Membranous Nephropathy. Kidney International, 107, 188-191. [Google Scholar] [CrossRef] [PubMed]
[30] 王清艳. Omi/HtrA2抑制剂对大鼠肾脏缺血/再灌注损伤诱导的肾小管上皮细胞凋亡的影响[D]: [硕士学位论文]. 晋中: 山西医科大学, 2009.
[31] Al-Rabadi, L.F., Caza, T., Trivin-Avillach, C., Rodan, A.R., Andeen, N., Hayashi, N., et al. (2021) Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy. Journal of the American Society of Nephrology, 32, 1666-1681. [Google Scholar] [CrossRef] [PubMed]