痛风性肾病致肾损伤的防治与研究
Research on Prevention and Treatment of Kidney Injury Caused by Gouty Nephropathy
DOI: 10.12677/tcm.2025.144184, PDF,   
作者: 史粮坤*, 黄 峥, 刘粮酺:广西中医药大学研究生院,广西 南宁;田君明#:广西中医药大学骨伤学院,广西 南宁
关键词: 尿酸痛风性肾病微分子机制肾纤维化Uric Acid Gouty Nephropathy Micromolecular Mechanism Renal Fibrosis
摘要: 近年来痛风的发病逐年增加,已成为人体代谢疾病的常客之一,对于其带来的肾脏方面的损害更是不容忽视。痛风性关节炎经久不治,或失治误治则会导致痛风性肾病的发生,而它的产生过程少不了高尿酸环境的影响,最终肾的损伤也与尿酸的影响关系密切。文章探究痛风所致肾损伤的相关研究,以期为临床和基础研究提供思路。
Abstract: In recent years, the incidence of gout has increased year by year, and it has become one of the most frequent cases of human metabolic diseases. The damage to the kidneys caused by gout cannot be ignored. Gouty arthritis can lead to the occurrence of gouty nephropathy if it is left untreated for a long time or improperly treated, and its production process is indispensable to the influence of a high uric acid environment. Finally, kidney damage is also closely related to the influence of uric acid. The article explores the relevant research on kidney injury caused by gout, aiming to provide ideas for clinical and basic research.
文章引用:史粮坤, 田君明, 黄峥, 刘粮酺. 痛风性肾病致肾损伤的防治与研究[J]. 中医学, 2025, 14(4): 1232-1240. https://doi.org/10.12677/tcm.2025.144184

参考文献

[1] Ponticelli, C., Podestà, M.A. and Moroni, G. (2020) Hyperuricemia as a Trigger of Immune Response in Hypertension and Chronic Kidney Disease. Kidney International, 98, 1149-1159. [Google Scholar] [CrossRef] [PubMed]
[2] 张玲, 黎颖, 张太君, 等. 慢性高尿酸血症肾病的中医防治研究进展[J]. 实用中西医结合临床, 2019, 19(6): 179-180.
[3] Bao, R., Liu, M., Wang, D., Wen, S., Yu, H., Zhong, Y., et al. (2019) Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice. Frontiers in Pharmacology, 10, Article No. 1464. [Google Scholar] [CrossRef] [PubMed]
[4] Li, X., Liu, J., Ma, L. and Fu, P. (2019) Pharmacological Urate-Lowering Approaches in Chronic Kidney Disease. European Journal of Medicinal Chemistry, 166, 186-196. [Google Scholar] [CrossRef] [PubMed]
[5] Xu, W., Huang, Y., Li, L., Sun, Z., Shen, Y., Xing, J., et al. (2016) Hyperuricemia Induces Hypertension through Activation of Renal Epithelial Sodium Channel (ENaC). Metabolism, 65, 73-83. [Google Scholar] [CrossRef] [PubMed]
[6] Ghasemi, A. (2021) Uric Acid‐Induced Pancreatic β-Cell Dysfunction. BMC Endocrine Disorders, 21, Article No. 24. [Google Scholar] [CrossRef] [PubMed]
[7] Zoccali, C. and Mallamaci, F. (2017) Uric Acid in Chronic Kidney Disease: The Quest for Causality Continues. Nephrology Dialysis Transplantation, 33, 193-195. [Google Scholar] [CrossRef] [PubMed]
[8] Liu, C., Ke, S., Tseng, G., Wu, Y. and Hwang, J. (2021) Elevated Serum Uric Acid Is Associated with Incident Hypertension in the Health According to Various Contemporary Blood Pressure Guidelines. Nutrition, Metabolism and Cardiovascular Diseases, 31, 1209-1218. [Google Scholar] [CrossRef] [PubMed]
[9] Kim, W., Go, T., Kang, D., Lee, J., et al. (2020) Age and Sex Dependent Association of Uric Acid and Incident Hypertension. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD, 31, 1200-1208.
[10] Cheung, K.W.K., van Groen, B.D., Spaans, E., van Borselen, M.D., de Bruijn, A.C.J.M., Simons‐Oosterhuis, Y., et al. (2019) A Comprehensive Analysis of Ontogeny of Renal Drug Transporters: mRNA Analyses, Quantitative Proteomics, and Localization. Clinical Pharmacology & Therapeutics, 106, 1083-1092. [Google Scholar] [CrossRef] [PubMed]
[11] Arakawa, H., Amezawa, N., Kawakatsu, Y. and Tamai, I. (2020) Renal Reabsorptive Transport of Uric Acid Precursor Xanthine by URAT1 and GLUT9. Biological and Pharmaceutical Bulletin, 43, 1792-1798. [Google Scholar] [CrossRef] [PubMed]
[12] Xin, Y., Wang, K., Jia, Z., Xu, T., Xu, Q., Zhang, C., et al. (2018) Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways. Cellular Physiology and Biochemistry, 47, 1074-1083. [Google Scholar] [CrossRef] [PubMed]
[13] Yong, T., Chen, S., Xie, Y., Chen, D., Su, J., Shuai, O., et al. (2018) Hypouricemic Effects of Ganoderma applanatum in Hyperuricemia Mice through OAT1 and GLUT9. Frontiers in Pharmacology, 8, Article No. 996. [Google Scholar] [CrossRef] [PubMed]
[14] Jin, Y., Lin, Z., Zhang, B. and Bai, Y. (2018) Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and in Vitro Verification with Cells. Evidence-Based Complementary and Alternative Medicine: eCAM, 2018, Article ID: 1764212. [Google Scholar] [CrossRef] [PubMed]
[15] Zhou, Y., Zhang, X., Li, C., Yuan, X., Han, L., Li, Z., et al. (2018) Research on the Pharmacodynamics and Mechanism of Fraxini Cortex on Hyperuricemia Based on the Regulation of URAT1 and GLUT9. Biomedicine & Pharmacotherapy, 106, 434-442. [Google Scholar] [CrossRef] [PubMed]
[16] Yu, X., Zhang, L., Zhang, P., Zhi, J., Xing, R. and He, L. (2020) Lycium barbarum Polysaccharides Protect Mice from Hyperuricaemia through Promoting Kidney Excretion of Uric Acid and Inhibiting Liver Xanthine Oxidase. Pharmaceutical Biology, 58, 944-949. [Google Scholar] [CrossRef] [PubMed]
[17] Deng, J., Jiang, W., Chen, C., Lee, L., Li, P., Huang, W., et al. (2020) Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-B/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 7912763. [Google Scholar] [CrossRef] [PubMed]
[18] Fan, Y., Liang, Z., Zhang, J. and You, G. (2021) Oral Proteasomal Inhibitors Ixazomib, Oprozomib, and Delanzomib Upregulate the Function of Organic Anion Transporter 3 (OAT3): Implications in OAT3-Mediated Drug-Drug Interactions. Pharmaceutics, 13, Article No. 314. [Google Scholar] [CrossRef] [PubMed]
[19] Kobayashi, M., Mizutani, A., Okamoto, T., Muranaka, Y., Nishi, K., Nishii, R., et al. (2021) Assessment of Drug Transporters Involved in the Urinary Secretion of [99mtc]dimercaptosuccinic Acid. Nuclear Medicine and Biology, 94, 92-97. [Google Scholar] [CrossRef] [PubMed]
[20] Chen, C., Tseng, C., Yen, J., Chang, J., Chou, W., Chu, H., et al. (2018) ABCG2 Contributes to the Development of Gout and Hyperuricemia in a Genome-Wide Association Study. Scientific Reports, 8, Article No. 3137. [Google Scholar] [CrossRef] [PubMed]
[21] Li, X., Chu, F., Jiang, S., et al. (2021) Preliminary Study on Effect of Phellinus igniarius Ethanol Extract on Serum Uric Acid Metabolism and Gut Microbiome in Rats. China Journal of Chinese Materia Medica, 46, 177-182.
[22] Gao, Y., Sun, J., Zhang, Y., Shao, T., Li, H., Wang, M., et al. (2020) Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria. Evidence-Based Complementary and Alternative Medicine: eCAM, 2020, Article ID: 8831937. [Google Scholar] [CrossRef] [PubMed]
[23] Xiong, C., Deng, J., Wang, X., Shao, X., Zhou, Q., Zou, H., et al. (2021) Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats. Frontiers in Pharmacology, 12, Article ID: 636154. [Google Scholar] [CrossRef] [PubMed]
[24] Leask, M.P., Sumpter, N.A., Lupi, A.S., Vazquez, A.I., Reynolds, R.J., Mount, D.B., et al. (2020) The Shared Genetic Basis of Hyperuricemia, Gout, and Kidney Function. Seminars in Nephrology, 40, 586-599. [Google Scholar] [CrossRef] [PubMed]
[25] Otani, N., Kurata, Y., Maharani, N., Kuwabara, M., Ikeda, N., Notsu, T., et al. (2020) Evidence for Urate Uptake through Monocarboxylate Transporter 9 Expressed in Mammalian Cells and Its Enhancement by Heat Shock. Circulation Reports, 2, 425-432. [Google Scholar] [CrossRef] [PubMed]
[26] Kasahara, M., Kuwabara, Y., Moriyama, T., Tanabe, K., Satoh-Asahara, N., Katsuya, T., et al. (2019) Intensive Uric Acid-Lowering Therapy in CKD Patients: The Protocol for a Randomized Controlled Trial. Clinical and Experimental Nephrology, 24, 235-241. [Google Scholar] [CrossRef] [PubMed]
[27] Martinon, F. (2009) Mechanisms of Uric Acid Crystal‐Mediated Autoinflammation. Immunological Reviews, 233, 218-232. [Google Scholar] [CrossRef] [PubMed]
[28] Amaral, F.A., Costa, V.V., Tavares, L.D., Sachs, D., Coelho, F.M., Fagundes, C.T., et al. (2012) NLRP3 Inflammasome-Mediated Neutrophil Recruitment and Hypernociception Depend on Leukotriene B4 in a Murine Model of Gout. Arthritis & Rheumatism, 64, 474-484. [Google Scholar] [CrossRef] [PubMed]
[29] Chen, Z., Sun, X., Li, X., Xu, Z., Yang, Y., Lin, Z., et al. (2020) Polydatin Attenuates Renal Fibrosis in Diabetic Mice through Regulating the Cx32-Nox4 Signaling Pathway. Acta Pharmacologica Sinica, 41, 1587-1596. [Google Scholar] [CrossRef] [PubMed]
[30] Chen, X., Ge, H., Lei, S., Jiang, Z., Su, J., He, X., et al. (2020) Dendrobium officinalis Six Nostrum Ameliorates Urate Under-Excretion and Protects Renal Dysfunction in Lipid Emulsion-Induced Hyperuricemic Rats. Biomedicine & Pharmacotherapy, 132, Article ID: 110765. [Google Scholar] [CrossRef] [PubMed]
[31] Piani, F. and Johnson, R.J. (2021) Does Gouty Nephropathy Exist, and Is It More Common than We Think? Kidney International, 99, 31-33. [Google Scholar] [CrossRef] [PubMed]
[32] Lu, X., Zeng, R., Lin, J., Hu, J., Rong, Z., Xu, W., et al. (2019) Pharmacological Basis for Use of Madecassoside in Gouty Arthritis: Anti-Inflammatory, Anti-Hyperuricemic, and NLRP3 Inhibition. Immunopharmacology and Immunotoxicology, 41, 277-284. [Google Scholar] [CrossRef] [PubMed]
[33] Ma, C., Kang, L., Ren, H., Zhang, D. and Kong, L. (2015) Simiao Pill Ameliorates Renal Glomerular Injury via Increasing Sirt1 Expression and Suppressing NF-κB/NLRP3 Inflammasome Activation in High Fructose-Fed Rats. Journal of Ethnopharmacology, 172, 108-117. [Google Scholar] [CrossRef] [PubMed]
[34] Lv, Y., Bing, Q., Lv, Z., Xue, J., Li, S., Han, B., et al. (2020) Imidacloprid-Induced Liver Fibrosis in Quails via Activation of the TGF-Beta1/Smad Pathway. Science of the Total Environment, 705, Article ID: 135915. [Google Scholar] [CrossRef] [PubMed]
[35] Kim, S., Lee, S., Kim, Y., Kim, S., Seo, J., Choi, Y., et al. (2015) Hyperuricemia-Induced NLRP3 Activation of Macrophages Contributes to the Progression of Diabetic Nephropathy. American Journal of Physiology-Renal Physiology, 308, F993-F1003. [Google Scholar] [CrossRef] [PubMed]
[36] Tan, J., Wan, L., Chen, X., Li, X., Hao, X., Li, X., et al. (2019) Conjugated Linoleic Acid Ameliorates High Fructose‐Induced Hyperuricemia and Renal Inflammation in Rats via NLRP3 Inflammasome and TLR4 Signaling Pathway. Molecular Nutrition & Food Research, 63, e1801402. [Google Scholar] [CrossRef] [PubMed]
[37] Zhao, H., Xu, J., Wang, R., Tang, W., Kong, L., Wang, W., et al. (2021) Plantaginis Semen Polysaccharides Ameliorate Renal Damage through Regulating NLRP3 Inflammasome in Gouty Nephropathy Rats. Food & Function, 12, 2543-2553. [Google Scholar] [CrossRef] [PubMed]
[38] Grainger, R., McLaughlin, R.J., Harrison, A.A. and Harper, J.L. (2012) Hyperuricaemia Elevates Circulating CCL2 Levels and Primes Monocyte Trafficking in Subjects with Inter-Critical Gout. Rheumatology, 52, 1018-1021. [Google Scholar] [CrossRef] [PubMed]
[39] Bahadoran, Z., Mirmiran, P., Kashfi, K. and Ghasemi, A. (2021) Hyperuricemia-Induced Endothelial Insulin Resistance: The Nitric Oxide Connection. Pflügers ArchivEuropean Journal of Physiology, 474, 83-98. [Google Scholar] [CrossRef] [PubMed]
[40] 中华医学会内分泌学分会. 中国高尿酸血症与痛风诊疗指南(2019) [J]. 中华内分泌代谢杂志, 2020, 36(1): 1-13.
[41] Khanna, P., Johnson, R.J., Marder, B., LaMoreaux, B. and Kumar, A. (2020) Systemic Urate Deposition: An Unrecognized Complication of Gout? Journal of Clinical Medicine, 9, Article No. 3204. [Google Scholar] [CrossRef] [PubMed]
[42] 万学红, 卢雪峰. 诊断学[M]. 第9版. 北京: 人民卫生出版社, 2018: 341-345.
[43] Stamp, L.K., Chapman, P.T., Barclay, M.L., Horne, A., Frampton, C., Tan, P., et al. (2017) A Randomised Controlled Trial of the Efficacy and Safety of Allopurinol Dose Escalation to Achieve Target Serum Urate in People with Gout. Annals of the Rheumatic Diseases, 76, 1522-1528. [Google Scholar] [CrossRef] [PubMed]
[44] 徐佩, 魏雪菲, 李菡, 等. 不同肾小球滤过率估算公式对估算慢性肾脏病患者肾小球滤过率的差异比较[J]. 现代医学, 2018, 46(9) : 978-983.
[45] 周妍, 李靖, 赵鑫宇, 等. 中西医结合治疗尿酸性肾病的随机对照试验中结局指标的选择[J]. 世界中医药, 2023, 18(9): 1260-1264.
[46] 邵忠林. 针药联合治疗湿热内蕴、肝肾不足型慢性尿酸性肾病的临床观察[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2020.
[47] 陈松鹤, 俞鸿晖, 方芝嫔, 等. 中医药治疗痛风性肾病的进展概述[J]. 中国中医急症, 2020, 29(10): 1877-1880.
[48] 林志帅, 鲁盈. 痛风性肾病中医辨治浅述[J]. 浙江中医杂志, 2019, 54(5): 382.
[49] 回鲁金, 董志刚. 董志刚辨治痛风性肾病经验[J]. 湖南中医杂志, 2016, 32(4): 32-33.
[50] 李春胜, 李卫东, 刘燕. 非布司他治疗G3期慢性肾脏病伴无症状高尿酸血症的临床效果及对患者肾功能的保护作用[J]. 中国临床药学杂志, 2021, 30(1): 1-4.
[51] Tien, Y., Shih, M., Tien, C., Huang, H. and Tu, Y. (2022) To Treat or Not to Treat? Effect of Urate-Lowering Therapy on Renal Function, Blood Pressure and Safety in Patients with Asymptomatic Hyperuricemia: A Systematic Review and Network Meta-Analysis. The Journal of the American Board of Family Medicine, 35, 140-151. [Google Scholar] [CrossRef] [PubMed]
[52] Waheed, Y., Yang, F. and Sun, D. (2021) Role of Asymptomatic Hyperuricemia in the Progression of Chronic Kidney Disease and Cardiovascular Disease. The Korean Journal of Internal Medicine, 36, 1281-1293. [Google Scholar] [CrossRef] [PubMed]
[53] 安琦, 王珂, 史恒军. 痛风辨证施治中顾护脾胃的探讨[J]. 陕西中医, 2015, 36(3): 385.
[54] 郝晓娟, 姜星, 范军. 中医治疗尿酸性肾病相关研究进展[J]. 中国现代医药杂志, 2020, 22(11): 100-103.
[55] 魏若妍, 张源, 张复亮, 等. 上海市徐家汇街道老年人高尿酸血症、痛风患病状况及影响因素研究[J]. 中国全科医学, 2019, 22(16): 1954-1959, 1972.
[56] Rodenbach, K.E., Schneider, M.F., Furth, S.L., Moxey-Mims, M.M., Mitsnefes, M.M., Weaver, D.J., et al. (2015) Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study. American Journal of Kidney Diseases, 66, 984-992. [Google Scholar] [CrossRef] [PubMed]
[57] Aiumtrakul, N., Wiputhanuphongs, P., Supasyndh, O. and Satirapoj, B. (2020) Hyperuricemia and Impaired Renal Function: A Prospective Cohort Study. Kidney Diseases, 7, 210-218. [Google Scholar] [CrossRef] [PubMed]
[58] Fukuda, A., Wickman, L.T., Venkatareddy, M.P., Wang, S.Q., Chowdhury, M.A., Wiggins, J.E., et al. (2012) Urine Podocin: Nephrin mRNA Ratio (PNR) as a Podocyte Stress Biomarker. Nephrology Dialysis Transplantation, 27, 4079-4087. [Google Scholar] [CrossRef] [PubMed]