黄秀荣,马 静

IgA肾病（IgAN）是最常见的原发性肾小球肾炎，临床表现多样，病理异质性强，约20%–40%的患者在10–20年内进展至终末期肾病。维生素D缺乏在IgAN患者中普遍存在，近年来大量研究显示血清25-羟基维生素D水平与蛋白尿、肾功能、贫血等临床指标密切相关，并与肾小管萎缩/间质纤维化（T病变）等牛津分型指标显著相关。本文系统综述维生素D与IgAN临床病理相关性的研究进展，重点阐述维生素D缺乏的流行病学、影响因素及其与临床指标和病理改变的关系，总结维生素D补充治疗的临床证据，并探讨维生素D受体（VDR）表达下调及TGF-β1/Smad、IL-23/IL-17等信号通路在其中的分子机制。现有证据支持将血清25(OH)D检测纳入IgAN常规评估，对缺乏者尤其是合并T病变的患者积极补充维生素D可能延缓肾脏病进展，但未来仍需高质量随机对照试验明确最佳干预方案。

IgA肾病；维生素D；25-羟基维生素D；临床病理；肾纤维化；维生素D受体

[1] Lee M,Suzuki H,Nihei Y,et al.Ethnicity and IgA nephropathy:worldwide differences in epidemiology,timing of diagnosis,clinical manifestations,management and prognosis.Clin Kidney J.2023;16(Suppl 2):ii1-ii8. [2] Kostadinova I,Lyubomirova M,Bogov B,et al.Clinical and epidemiological study of IgA nephropathy in the Bulgarian population: insights into disease presentation and potential biomarkers.J Pers Med.2024;14(3):231. [3] Glassock RJ.IgA nephropathy:"The times they are a-changin".Glomerular Dis.2022;2(1):4-14. [4] Filippone EJ,Gulati R,Farber JL.Contemporary review of IgA nephropathy.Front Immunol.2024;15:1436923. [5] Howie AJ,Lalayiannis AD.Systematic review of the Oxford classification of IgA nephropathy:reproducibility and prognostic value.Kidney360.2023;4(8):1103-1111. [6] Haussler MR,Haussler CA,Jurutka PW.Genomically anchored vitamin D receptor mediates an abundance of bioprotective actions elicited by its 1,25-dihydroxyvitamin D hormonal ligand.Vitam Horm.2023;123:313-383. [7] Chen S,Chen H,Chen X,et al.Bidirectional Mendelian randomization analysis of the causal associations between serum vitamin D levels and multiple kidney diseases.Sci Rep.2025;15(1):23908. [8] Gembillo G,Siligato R,Amatruda M,et al.Vitamin D and glomerulonephritis.Medicina(Kaunas).2021;57(2):164. [9] 邓梅秋.IgA肾病患者血清25(OH)D水平及其影响因素研究[D].广西医科大学,2019. [10] 苏长权,罗美华,尤燕华,等.维生素D₂肌注治疗IgA肾病患者维生素D缺乏的临床观察[J].中国中西医结合肾病杂志,2022,23(3):212-215. [11] L u F,Liu C,Song D,et al.Effect of time-weighted average 25(OH)D on the occurrence of major adverse kidney events in IgA nephropathy—from a 10-year population-based cohort study.Front Nutr.2025;12:1576488. [12] Farooqui N,Subbiah A,Chaturvedi P,et al.Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy.BMC Nephrol.2023;24(1):15. [13] Abilov T,Ismailova I,Shaimbetov Z,et al.Impact of vitamin D metabolism disorders on the development of autoimmune kidney diseases:a systematic review.Georgian Med News.2024;(363):23-30. [14] ArapovićA,VukojevićK,Glavina Durdov M,et al.Expression of renal vitamin D receptors and metabolizing enzymes in IgA nephropathy.Acta Histochem.2021;123(5):151740. [15] Takiguchi R,Nishi S,Goto S,et al.Effect of bisphosphonate and active vitamin D analog on glucocorticoid-induced osteoporosis in patients with IgA nephropathy:a retrospective observational study.Kobe J Med Sci.2023;69(1):E9-E15. [16] 宋丹丹,孙连芹,朱敬凤,等.维生素D缺乏与IgA肾病患者肾脏预后的关系[J].南京医科大学学报(自然科学版),2023,43(1):53-59. [17] Cimini FA,Sentinelli F,Oldani A,et al.Adipose tissue dysfunction and metabolic diseases:the role of vitamin D/vitamin D receptor axis.Int J Mol Sci.2025;26(21):10112. [18] Melguizo-Rodríguez L,Costela-Ruiz VJ,García-Recio E,et al.Role of vitamin D in the metabolic syndrome.Nutrients.2021;13(3):830. [19] Hajare AD,Dagar N,Gaikwad AB.Klotho antiaging protein:molecular mechanisms and therapeutic potential in diseases.Mol Biomed.2025;6(1):19. [20] Charoenngam N,Holick MF.Immunologic effects of vitamin D on human health and disease.Nutrients.2020;12(7):2097. [21] Zhang Q,Jiang X,Wen D,et al.Vitamin D receptor/vitamin D response element directly modulate Nestin transcription to ameliorate PAN-induced podocyte morphological changes.Nephron.2022;146(6):624-636. [22] 周苏雅,王昱,陈凯,等.维生素D受体在IgA肾病患者肾脏中的表达及其与肾纤维化的关系[J].中国中西医结合肾病杂志,2024, 25(6):498-502. [23] Wanyan X,Xu J.Clinical efficacy of vitamin D supplements for the treatment of anemia in patients with chronic kidney disease:a systematic review and meta-analysis.Hemodial Int.2026;30(2):170-180. [24] 李敬,李鹤,赵婷.慢性肾脏病患者血清维生素D水平在整体营养状况评价中的应用及其意义[J].吉林大学学报(医学版),2019, 45(5):1147-1152. [25] 彭莉.1,25-二羟维生素D₃对IgA肾病大鼠中IL-23/IL-17轴的调节作用[D].山西医科大学,2016. [26] 何国华,容丽萍,姜梦婕,等.IgA肾病大鼠尿维生素D结合蛋白与肾脏纤维化关系的研究[J].中国现代医学杂志,2018,28(24):1-5. [27] 孙达,王娇姣,王力宁,等.25羟基维生素D₃与IgA肾病临床病理关系研究[J].中国实用内科杂志,2016,36(6):472-475. [28] 李优.维生素D联合羟氯喹对IgA肾病大鼠的治疗作用研究[D].中国医科大学,2020. [29] Xiong XR,Tian XL,Huo RJ,et al.1α,25-dihydroxyvitamin D3 inhibits transforming growth factorβ1-induced epithelial-mesenchymal transition viaβ-catenin pathway.Chin Med J.2020;133(11):1298-1303. [30] Zhang C,Tong T,Miao DC,et al.Vitamin D inhibits TNF-αinduced apoptosis of human nucleus pulposus cells through regulation of NF-κB signaling pathway.J Orthop Surg Res.2021;16(1):411. [31] Ali A,Shah SA,Zaman N,et al.Vitamin D exerts neuroprotection via SIRT1/nrf-2/NF-κB signaling pathways against D-galactose- induced memory impairment in adult mice.Neurochem Int.2021;142:104893. [32] Krebs CF,Turner JE,Riedel JH,et al.Tissue-specific therapy in immune-mediated kidney diseases:new ARGuments for targeting the IL-23/IL-17 axis.J Clin Invest.2021;131(12):e150588. [33] Nakhoul N,Thawko T,Farber E,et al.The therapeutic effect of active vitamin D supplementation in preventing the progression of diabetic nephropathy in a diabetic mouse model.J Diabetes Res.2020;2020:7907605. [34] Metin H,Ertan P,Keskinoğlu A,et al.Effect of vitamin D analogues calcitriol and paricalcitol in a rat model of puromycin aminonucleoside-induced nephrotic syndrome.Paediatr Indones.2022;62(6):382-389. [35] 师旭辉,于建军.活性维生素D(VD₃)+厄贝沙坦对IgA肾病患者肾功能及Nephrin､Podocin表达调控作用[J].临床研究,2020, 28(10):118-119. [36] Zhang X,Zhang L,Wen Y,et al.Vitamin D ameliorates podocyte injury by enhancing autophagy activity in diabetic kidney disease.Kidney Blood Press Res.2023;48(1):314-325. [37] Shi L,Xiao C,Zhang Y,et al.Vitamin D/vitamin D receptor/Atg16L1 axis maintains podocyte autophagy and survival in diabetic kidney disease.Ren Fail.2022;44(1):694-705. [38] Abo-Zaid MA,Hamdi HA,Elashmawy NF.Vitamin D and immunity:a comprehensive review of its impact on autoimmunity,allergy suppression,antimicrobial defense,and cancer inhibition.Egypt J Immunol.2023;30(4):47-66. [39] 张婷.活性维生素D､血管紧张素受体拮抗剂联合治疗IgA肾病的疗效及安全性[J].中国社区医师,2018,34(30):79-81. [40] 叶琨,彭小梅,韦俏宇,等.活性维生素D联合厄贝沙坦治疗IgA肾病的疗效及其对T细胞亚群的影响:随机对照试验[J].中国全科医学,2013,16(26):2327-2330.

点击下载PDF