Klotho在血液净化患者中的研究进展
Research Progress of Klotho Gene in Blood Purification
DOI: 10.12677/acm.2026.161278, PDF,   
作者: 董晓辉, 张 静：同济大学附属东方医院胶州医院肾内科，山东 青岛；吕希峰*：同济大学附属东方医院胶州医院重症医学科，山东 青岛
关键词: Klotho；血液净化；血管钙化；矿物质代谢；氧化应激；Klotho Gene； Blood Purification； Vascular Calcification； Mineral Metabolism Disorders； Oxidative Stress
摘要: Klotho是一种抗衰老基因，主要表达于肾脏、脑组织和甲状旁腺；研究表明Klotho基因的许多生物学功能在血液净化患者中发挥重大作用。本文对该基因在血液净化患者中的作用进行了综述，探讨其在血液净化患者中的影响。
Abstract: The gene of klotho is associated with aging that is mainly expressed in the kidneys, brain tissues and parathyroid glands. The biological functions of Klotho gene have been demonstrated to play an important role in patients with blood purification. The review is about an effect of this gene on blood purification and explores its role in patients undergoing blood purification.
文章引用：董晓辉, 张静, 吕希峰. Klotho在血液净化患者中的研究进展[J]. 临床医学进展, 2026, 16(1): 2208-2214. https://doi.org/10.12677/acm.2026.161278

参考文献

[1] Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., et al. (1997) Mutation of the Mouse Klotho Gene Leads to a Syndrome Resembling Ageing. Nature, 390, 45-51. [Google Scholar] [CrossRef] [PubMed]
[2] Hu, M.C., Kuro-o, M. and Moe, O.W. (2013) Renal and Extrarenal Actions of Klotho. Seminars in Nephrology, 33, 118-129. [Google Scholar] [CrossRef] [PubMed]
[3] 袁群生, 李雪梅. 2017年KDIGO关于慢性肾脏病矿物质及骨异常临床实践指南更新与解读[J]. 协和医学杂志, 2018, 9(3): 213-218.
[4] Koh, N., Fujimori, T., Nishiguchi, S., Tamori, A., Shiomi, S., Nakatani, T., et al. (2001) Severely Reduced Production of Klotho in Human Chronic Renal Failure Kidney. Biochemical and Biophysical Research Communications, 280, 1015-1020. [Google Scholar] [CrossRef] [PubMed]
[5] Mitani, H., Ishizaka, N., Aizawa, T., Ohno, M., Usui, S., Suzuki, T., et al. (2002) In Vivo Klotho Gene Transfer Ameliorates Angiotensin II-Induced Renal Damage. Hypertension, 39, 838-843. [Google Scholar] [CrossRef] [PubMed]
[6] 林书典, 詹锋, 武伟, 等. 可溶性Klotho蛋白与慢性肾脏病患者体内氧化应激的关系研究[J]. 中国全科医学, 2016, 19(11): 1297-1300.
[7] Aizawa, H., Saito, Y., et al. (2005) Downregulation of the Klotho Gene in the Kidney under Sustained Circulatory Stress in Rats. Nephrol Dial Transplant, 101, 112-115.
[8] 张育安, 杨玉琼, 周盛, 等. 组合式透析与单纯透析对血液透析患者并发症及死亡率的影[J]. 中国中西医结合肾病杂志, 2021, 22(1): 66-68.
[9] 巩楠, 张学强, 袁铮, 等. 维持性血液透析患者全因死亡相关危险因素分析[J]. 中国中西医结合肾病杂志, 2021, 22(1): 62-63.
[10] 陈琰, 郑淑蓓, 金领微, 等. 维持性血液透析患者镁代谢紊乱与冠状动脉钙化的相关性分析[J]. 中华肾脏病杂志, 2017, 33(2): 106-111.
[11] 郑淑蓓, 郑育, 李占园, 等. 成纤维细胞生长因子23-Klotho蛋白与血液透析患者骨密度改变的关[J]. 中华肾脏病杂志, 2016, 32(5): 321-326.
[12] Atapour, A., Eshaghian, A., Taheri, D. and Dolatkhah, S. (2015) Hemodialysis versus Peritoneal Dialysis, Which Is Cost-Effective? Saudi Journal of Kidney Diseases and Transplantation, 26, 962-965. [Google Scholar] [CrossRef] [PubMed]
[13] 贾琳, 陈文莉, 黎妮, 等. 可溶性Klotho蛋白对维持性血液透析患者血管硬化的影响[J]. 临床肾脏病杂志, 2015, 15(1): 30-34.
[14] 王玉英, 贾顺莲, 高新英, 等. 维持性透析患者血清FGF23和Klotho蛋白与钙磷代谢、动脉硬化和左心室肥厚的关系[J]. 江苏医药, 2017, 43(7): 21-24.
[15] Paloian, N.J. and Giachelli, C.M. (2014) A Current Understanding of Vascular Calcification in CKD. American Journal of Physiology-Renal Physiology, 307, F891-F900. [Google Scholar] [CrossRef] [PubMed]
[16] Esapa, C.T., Hannan, F.M., Babinsky, V.N., Potter, P., Thomas, G.P., Croucher, P.I., et al. (2015) N-Ethyl-N-Nitrosourea (ENU) Induced Mutations within the Klotho Gene Lead to Ectopic Calcification and Reduced Lifespan in Mouse Models. PLOS ONE, 10, e0122650. [Google Scholar] [CrossRef] [PubMed]
[17] Pavlatou, M.G., Remaley, A.T. and Gold, P.W. (2016) Klotho: A Humeral Mediator in CSF and Plasma That Influences Longevity and Susceptibility to Multiple Complex Disorders, Including Depression. Translational Psychiatry, 6, e876. [Google Scholar] [CrossRef] [PubMed]
[18] Oliveira, R.B.d., Okazaki, H., Stinghen, A.E.M., Drüeke, T.B., Massy, Z.A. and Jorgetti, V. (2013) Vascular Calcification in Chronic Kidney Disease: A Review. Jornal Brasileiro de Nefrologia, 35, 147-161. [Google Scholar] [CrossRef] [PubMed]
[19] Jasani, R., Hase, N., Kumar, R., Dedhia, P., Jamale, T. and Bajpai, D. (2018) Predictors of Coronary Calcification in Indian Hemodialysis Patients. Saudi Journal of Kidney Diseases and Transplantation, 29, 822-827. [Google Scholar] [CrossRef] [PubMed]
[20] Liberman, M., Pesaro, A.E.P., Carmo, L.S. and Serrano Jr, C.V. (2013) Calcificação vascular: fisiopatologia e implicações clínicas. Einstein (São Paulo), 11, 376-382. [Google Scholar] [CrossRef] [PubMed]
[21] 盛亚楠, 赵东明, 马千里, 等. 慢性肾脏疾病患者心外膜脂肪体积与冠状动脉钙化的相关性研究[J]. 中华心血管病杂志, 2017, 45(2): 121-125.
[22] 李瑞霞, 李亚峰, 李荣山. 继发性甲状旁腺功能亢进症与血管钙化研究进展[J]. 中国分子心脏病学杂志, 2018, 18(2): 2442-2446.
[23] Kunert, S.K., Hartmann, H., Haffner, D. and Leifheit-Nestler, M. (2016) Klotho and Fibroblast Growth Factor 23 in Cerebrospinal Fluid in Children. Journal of Bone and Mineral Metabolism, 35, 215-226. [Google Scholar] [CrossRef] [PubMed]
[24] Hu, M.C., Shiizaki, K., Kuro-o, M. and Moe, O.W. (2013) Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism. Annual Review of Physiology, 75, 503-533. [Google Scholar] [CrossRef] [PubMed]
[25] Lang, F., Leibrock, C., Pandyra, A.A., Stournaras, C., Wagner, C.A. and Föller, M. (2018) Phosphate Homeostasis, Inflammation and the Regulation of FGF-23. Kidney and Blood Pressure Research, 43, 1742-1748. [Google Scholar] [CrossRef] [PubMed]
[26] Disthabanchong, S. (2018) Phosphate and Cardiovascular Disease Beyond Chronic Kidney Disease and Vascular Calcification. International Journal of Nephrology, 2018, Article ID: 3162806. [Google Scholar] [CrossRef] [PubMed]
[27] 郑淑蓓, 金领微, 李占园. 维持性血液透析患者冠状动脉钙化的评价及影响因素分析[J]. 中华肾脏病杂志, 2015, 31(5): 339-344.
[28] 王婷. 慢性肾脏病3-5期血清Klotho蛋白及1,25(OH)2D3水平的变化及其与钙磷代谢的关系[D]: [硕士学位论文]. 福州: 福建中医药大学, 2018.
[29] Razzaque, M.S. (2009) The FGF23-Klotho Axis: Endocrine Regulation of Phosphate Homeostasis. Nature Reviews Endocrinology, 5, 611-619. [Google Scholar] [CrossRef] [PubMed]
[30] Quarles, L.D. (2009) Endocrine Functions of Bone in Mineral Metabolism Regulation. Journal of Clinical Investigation, 119, 421-421. [Google Scholar] [CrossRef] 
[31] Shimada, T., Yamazaki, Y., Takahashi, M., Hasegawa, H., Urakawa, I., Oshima, T., et al. (2005) Vitamin D Receptor-Independent FGF23 Actions in Regulating Phosphate and Vitamin D Metabolism. American Journal of Physiology-Renal Physiology, 289, F1088-F1095. [Google Scholar] [CrossRef] [PubMed]
[32] Bahar, G.D., Siren, S., Saliha, U.Y., et al. (2018) FGF23, NGAL, and Endostatin: The Predictors of Allograft Function in Renal Transplant Recipients. Experimental and Clinical Transplantation, 16, 136-139.
[33] Kuro-o, M. (2018) Klotho and Endocrine Fibroblast Growth Factors: Markers of Chronic Kidney Disease Progression and Cardiovascular Complications? Nephrology Dialysis Transplantation, 34, 15-21. [Google Scholar] [CrossRef] [PubMed]
[34] Xu, R., Han, Q., Zhu, T., Ren, Y., Chen, J., Zhao, H., et al. (2012) Impact of Individual and Environmental Socioeconomic Status on Peritoneal Dialysis Outcomes: A Retrospective Multicenter Cohort Study. PLOS ONE, 7, e50766. [Google Scholar] [CrossRef] [PubMed]
[35] Isakova, T., Cai, X., Lee, J., Xie, D., Wang, X., Mehta, R., et al. (2018) Longitudinal FGF23 Trajectories and Mortality in Patients with CKD. Journal of the American Society of Nephrology, 29, 579-590. [Google Scholar] [CrossRef] [PubMed]
[36] Shalhoub, V., Shatzen, E.M., Ward, S.C., Davis, J., Stevens, J., Bi, V., et al. (2012) FGF23 Neutralization Improves Chronic Kidney Disease-Associated Hyperparathyroidism Yet Increases Mortality. Journal of Clinical Investigation, 122, 2543-2553. [Google Scholar] [CrossRef] [PubMed]
[37] 程虹, 李颖霞, 王小琴, 等. 慢性肾脏病3-5期患者病情程度与α-Klotho、FGF23及钙、磷相关性研究[J]. 中国医药导报, 2020, 17(22): 78-81.
[38] 贺西南, 石宏斌. 慢性肾脏病继发性甲状旁腺功能亢进的研究进展[J]. 中国中西医结合肾病杂志, 2019, 20(5): 456-459.
[39] 李贺, 张东亮. FGF23/klotho系统参与慢性肾脏病矿物质骨异常的研究进展[J]. 中国医师杂志, 2014, 16(4): 559-561.
[40] Hu, M.C., Kuro-o, M. and Moe, O.W. (2012) Secreted Klotho and Chronic Kidney Disease. In: Kuro-o, M., Ed., Endocrine FGFs and Klothos, Springer, 126-157. [Google Scholar] [CrossRef] [PubMed]
[41] Drüeke, T.B. (2010) Klotho, FGF23, and FGF Receptors in Chronic Kidney Disease: A Yin-Yang Situation? Kidney International, 78, 1057-1060. [Google Scholar] [CrossRef] [PubMed]
[42] 施丽丽, 任明山, 吴元洁. 糖尿病周围神经病变与氧化应激研究现状[J]. 安徽医科大学学报, 2012, 47(1): 94-96.
[43] Tettamanti, C., Hervet, T., Grabherr, S. and Palmiere, C. (2016) Elevation of NT-proBNP and Cardiac Troponins in Sepsis-Related Deaths: A Forensic Perspective. International Journal of Legal Medicine, 130, 1035-1043. [Google Scholar] [CrossRef] [PubMed]
[44] Tetta, C., Biasioli, S., Schiavon, R., Inguaggiato, P., David, S., Panichi, V., et al. (1999) An Overview of Haemodialysis and Oxidant Stress. Blood Purification, 17, 118-126. [Google Scholar] [CrossRef] [PubMed]
[45] Kayabasi, H., Sit, D., Atay, A.E., Yilmaz, Z., Kadiroglu, A.K. and Yilmaz, M.E. (2010) Parameters of Oxidative Stress and Echocardiographic Indexes in Patients on Dialysis Therapy. Renal Failure, 32, 328-334. [Google Scholar] [CrossRef] [PubMed]
[46] 梁敏, 侯凡凡, 田建伟, 等. 急性肾损伤生物标志物的研究进展[J]. 解放军医学杂志, 2003, 28(6): 540-541.
[47] Flessner, M.F. (2007) Inflammation from Sterile Dialysis Solutions and the Longevity of the Peritoneal Barrier. Clinical Nephrology, 68, 341-348. [Google Scholar] [CrossRef] [PubMed]
[48] Noh, H., Kim, J.S., Han, K., Lee, G.T., Song, J.S., Chung, S.H., et al. (2006) Oxidative Stress during Peritoneal Dialysis: Implications in Functional and Structural Changes in the Membrane. Kidney International, 69, 2022-2028. [Google Scholar] [CrossRef] [PubMed]
[49] Yamamoto, M., Clark, J.D., Pastor, J.V., Gurnani, P., Nandi, A., Kurosu, H., et al. (2005) Regulation of Oxidative Stress by the Anti-Aging Hormone Klotho. Journal of Biological Chemistry, 280, 38029-38034. [Google Scholar] [CrossRef] [PubMed]
[50] 刘爱英, 冯国徵, 孙秀丽. 血液透析与腹膜透析对终末期肾病患者血脂、氧化应激及炎症因子的影响[J]. 中国煤炭工业医学杂志, 2023, 23(1): 57-61.
[51] 徐庆东, 郭焕开, 陈小荷, 等. 腹膜透析和血液透析对终末期肾脏疾病患者钙磷代谢及炎症因子的影响[J]. 临床肾脏病杂志, 2017, 17(4): 226-229.
[52] 费丹峰, 朱鸣, 任凌燕, 等. 不同透析方式对终末期糖尿病肾病患者Klotho蛋白、FGF-23及颈动脉内膜中层厚度的影响[J]. 广东医学, 2022, 41(21): 2192-2195.
[53] 刘艾芹, 于磊, 朱立革, 等. 慢性肾脏病不同分期血清Klotho蛋白水平的变化及其意义[J]. 中国综合临床, 2019, 35(6): 536-537.
[54] Yang, K., Yang, J., Bi, X., Yu, Z., Xiao, T., Huang, Y., et al. (2020) Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease. Cardiorenal Medicine, 10, 175-187. [Google Scholar] [CrossRef] [PubMed]
[55] Lacroix, J.S. and Urena-Torres, P. (2020) Potentielle Application de l’axe Fibroblast Growth Factor 23-Klotho dans la maladie rénale chronique. Néphrologie & Thérapeutique, 16, 83-92. [Google Scholar] [CrossRef] [PubMed]
[56] 蔡宏, 张伟明, 祝旭颖, 等. 血清可溶性Klotho水平与维持性血液透析患者预后的关系[J]. 中华肾脏病杂志, 2017, 33(5): 334-341.
[57] 邓晓风, 代青, 万莉, 等. 多模式组合透析对维持性血液透析患者Klotho蛋白、FGF-23和BNP的影响[J]. 中华危重病急救医学杂志, 2017, 29(7): 636-639.
[58] Bello, A.K., Okpechi, I.G., Osman, M.A., Cho, Y., Htay, H., Jha, V., et al. (2022) Epidemiology of Haemodialysis Outcomes. Nature Reviews Nephrology, 18, 378-395. [Google Scholar] [CrossRef] [PubMed]

为你推荐