Education, Science, Technology, Innovation and Life
Open Access
Sign In
  1. Home
  2. Journals
  3. MEDS Clinical Medicine
  4. Vol 6, Issue 2, 2025

Advances in Uric Acid Metabolism Mechanisms under High-altitude Environments

Download as PDF

DOI: 10.23977/medsc.2025.060219 | Downloads: 11 | Views: 287

Author(s)

Yu He 1, Hong Liu 2, Run Ma 1, Weiji Yue 1

Affiliation(s)

1 Clinical Medical College, Dali University, Dali, Yunnan, China
2 The First Affiliated Hospital of Dali University, Dali, Yunnan, China

Corresponding Author

Hong Liu

ABSTRACT

Hyperuricemia (HUA) is a metabolic disease caused by disorders in purine metabolism, and its occurrence and progression are influenced by multiple factors including genetic and environmental factors. This article aims to review the impact of high-altitude environments on uric acid levels and the mechanisms of uric acid metabolism under such conditions.

KEYWORDS

High-altitude environments; Hyperuricemia; Uric acid

CITE THIS PAPER

Yu He, Hong Liu, Run Ma, Weiji Yue, Advances in Uric Acid Metabolism Mechanisms under High-altitude Environments. MEDS Clinical Medicine (2025) Vol. 6: 148-157. DOI: http://dx.doi.org/10.23977/medsc.2025.060219.

REFERENCES

[1] Arestegui, A.H., Fuquay, R., Sirota, J., Swenson, E.R., Schoene, R.B., Jefferson, J.A., Chen, W., Yu, X.Q., Kelly, J.P., Johnson, R.J., and Escudero, E. (2011). High altitude renal syndrome (HARS). J Am Soc Nephrol 22, 1963-1968. 10.1681/asn.2010121316.
[2] Wang, S.Y., Liang, J., and Zhao, J.H. (2024). A Case of High-Altitude Renal Syndrome. High Alt Med Biol 25, 149-151. 10.1089/ham.2023.0077. 
[3] Zhang, M., Zhu, X., Wu, J., Huang, Z., Zhao, Z., Zhang, X., Xue, Y., Wan, W., Li, C., Zhang, W., et al. (2021). Prevalence of Hyperuricemia among Chinese Adults: Findings From Two Nationally Representative Cross-Sectional Surveys in 2015-16 and 2018-19. Front Immunol 12, 791983. 10.3389/fimmu.2021.791983.
[4] Huang, J., Ma, Z.F., Zhang, Y., Wan, Z., Li, Y., Zhou, H., Chu, A., and Lee, Y.Y. (2020). Geographical distribution of hyperuricemia in Chinese mainland: a comprehensive systematic review and meta-analysis. Glob Health Res Policy 5, 52. 10.1186/s41256-020-00178-9.
[5] Yuan, Z., Zou, Y., Liu, X., Wang, L., and Chen, C. (2023). Longitudinal study on blood and biochemical indexes of Tibetan and Han in high altitude area. Front Public Health 11, 1282051. 10.3389/fpubh.2023.1282051.
[6] Zhao, W. J., Liu, L. J., Li, X. H., Wang, P. L., Jia, P., and Wang, Y. F. (2022). Epidemiological characteristics and risk factors of hyperuricemia and gout among adults in Inner Mongolia. Journal of Applied Preventive Medicine, 28(05), 421-425, 431.
[7] Zhang, H., Ma, L. F., Zhang, Z. Y., Jiang, Y. Q., Zhao, Y. D., Yang, L. H., Liang, T., Dong, W. X., Liu, L. J., Zhao, F. C., and Kang, L. L. (2020). Distribution characteristics of hypertension, fatty liver disease, and hyperuricemia among adult Tibetan residents: A community-based survey in Lhasa. Journal of Environmental and Occupational Medicine, 37(12), 1182-1187.
[8] Dong, J. H., Pang, H. and Zhao, L. Y. (2022). Status and related factors of hyperuricemia among Mongolian adults in Inner Mongolia from 2018 to 2020. Journal of Health Research, 51(6), 940-946.
[9] Wang, Y., Wang, H., Chen, Y., Xu, N., Lee, W., and Lam, W.K. (2022). Pulmonary Capacity, Blood Composition and Metabolism among Coal Mine Workers in High- and Low-Altitude Aboveground and Underground Workplaces. Int J Environ Res Public Health 19. 10.3390/ijerph19148295.
[10] Tang, Z. W., Liu, F. Y., Xu, G., Jiang, C. H., Guan, L. B., Huang, Q. Y. and Gao Y. Q. (2016). Epidemiological characteristics and genetic susceptibility of hyperuricemia among Han Chinese young males migrating to a plateau (4520 m). Medical Journal of the Chinese People's Liberation Army, 41(10), 859-864.
[11] Han, D., Yao, Y., Wang, F., He, W., Sun, T., and Li, H. (2024). A study on the correlation between hyperuricemia and TG/HDL-c ratio in the Naxi ethnic group at high-altitude regions of Yunnan. Front Med (Lausanne) 11, 1416021. 10.3389/fmed.2024.1416021. 
[12] Zhang, X., Meng, Q., Feng, J., Liao, H., Shi, R., Shi, D., Renqian, L., Langtai, Z., Diao, Y., and Chen, X. (2018). The prevalence of hyperuricemia and its correlates in Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China. Lipids Health Dis 17, 235. 10.1186/s12944-018-0882-6.
[13] Zila-Velasque, J.P., Grados-Espinoza, P., Challapa-Mamani, M.R., Sánchez-Alcántara, F., Cedillo-Balcázar, J., Cs, A.D., Hernandez-Bustamante, E.A., Tejada-Flores, J., Piano Suárez, A., Pacheco-Mendoza, J., and Benites-Zapata, V.A. (2024). Prevalence of metabolic syndrome and its components according to altitude levels: a systematic review and meta-analysis. Sci Rep 14, 27581. 10.1038/s41598-024-77928-z.
[14] Gao, C., Chen, Z., Ma, J., Xie, J., Zhang, W., Ren, H., and Chen, X. (2021). Prevalence of and risk factors for high-altitude hyperuricaemia in Bai individuals: a cross-sectional study. J Int Med Res 49, 3000605211028140. 10.1177/03000605211028140. 
[15] Cui, D., Huang, R., Yongzong, D., Lin, B., Huang, X., Ciren, Q., and Zhou, X. (2024). Gender-specific association between blood cell parameters and hyperuricemia in high-altitude areas. Front Public Health 12, 1336674. 10.3389/fpubh.2024.1336674.
[16] Jefferson, J.A., Escudero, E., Hurtado, M.E., Kelly, J.P., Swenson, E.R., Wener, M.H., Burnier, M., Maillard, M., Schreiner, G.F., Schoene, R.B., et al. (2002). Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis 39, 1135-1142. 10.1053/ajkd.2002.33380.
[17] Ouyang, Y., Zhang, Y., Li, H., Ma, L.B.Z., De Ji, C.R., Qiao, C., Dun, B., Gao, X., Zhu, J., Xu, P., et al. (2024). Effect of therapeutic erythrocytapheresis on outcomes and renal benefit in patients with high-altitude polycythemia: a real-world study. Sci Rep 14, 29081. 10.1038/s41598-024-80609-6.
[18] Sinha, S., Singh, S.N., and Ray, U.S. (2009). Total antioxidant status at high altitude in lowlanders and native highlanders: role of uric acid. High Alt Med Biol 10, 269-274. 10.1089/ham.2008.1082.
[19] Dong, H. M., Tian, G., Wang, Z. Q. and He, W. Y. (2020). Protective role of Klotho in adaptive responses of cardiomyocytes to chronic hypoxia at high altitude. Journal of Preventive Medicine of Chinese People's Liberation Army, 38(11), 95-97.
[20] Yang, G. Y., Xiong, Y. Z., Li, Y. Y., Ma,Y. C. and Liu, Z. L. (2010). Comparison of gastric mucosal XOD activity between indigenous Han populations in plateau and plain regions. Journal of Clinical Gastroenterology, 22(02), 74-75.
[21] Pu, L., Xu, H., Wang, Z., Li, R., Ai, C., Song, X., Zhang, L., Cheng, X., Wang, G., Wang, X., et al. (2024). Intermittent high altitude hypoxia induced liver and kidney injury leading to hyperuricemia. Arch Biochem Biophys 758, 110078. 10.1016/j.abb.2024.110078.
[22] Liu, H. F., Xia, Y., Xu, Q., Xiong, J. C., Zhao, J. H. and Li, Y. N. (2017). Role of hyperuricemia in inducing epithelial-mesenchymal transition of renal tubular epithelial cells via the TLR4/NF-κB signaling pathway. Journal of the Third Military Medical University, 39(19), 1919-1925.
[23] Dang, W., Li, F., Gao, R., Zhang, C., Cheng, H., Wu, Z., Yang, T., Pan, J., Tang, X., and Gao, Y. (2024). Protective Effects of Dioscin and Diosgenin on Plateau Hyperuricemia by Attenuating Renal Inflammation via EPHX2. Int J Mol Sci 25. 10.3390/ijms252413399.
[24] Miao, C. X., and Leng, J. H. (2024). Research progress on pharmacological effects and mechanisms of dioscin. Chinese Archives of Traditional Chinese Medicine, 42(11), 113-118.
[25] Brooks, G.A. (2020). Lactate as a fulcrum of metabolism. Redox Biol 35, 101454. 10.1016/j.redox.2020.101454.
[26] Dong, S., Qian, L., Cheng, Z., Chen, C., Wang, K., Hu, S., Zhang, X., and Wu, T. (2021). Lactate and Myocardiac Energy Metabolism. Front Physiol 12, 715081. 10.3389/fphys.2021.715081.
[27] Brooks, G.A. (2018). The Science and Translation of Lactate Shuttle Theory. Cell Metab 27, 757-785. 10.1016/j.cmet.2018.03.008.
[28] Su, Q., Li, Y.C., Zhuang, D.H., Liu, X.Y., Gao, H., Li, D., Chen, Y., Ge, M.X., Han, Y.M., Gao, Z.L., et al. (2024). Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans. Mol Biol Evol 41. 10.1093/molbev/msae233.
[29] Zhang, D., Tang, Z., Huang, H., Zhou, G., Cui, C., Weng, Y., Liu, W., Kim, S., Lee, S., Perez-Neut, M., et al. (2019). Metabolic regulation of gene expression by histone lactylation. Nature 574, 575-580. 10.1038/s41586-019-1678-1.
[30] Chen, X., Liu, L., Kang, S., Gnanaprakasam, J.R., and Wang, R. (2023). The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation. Sci Adv 9, eadd9554. 10.1126/sciadv.add9554.
[31] Lopez Krol, A., Nehring, H.P., Krause, F.F., Wempe, A., Raifer, H., Nist, A., Stiewe, T., Bertrams, W., Schmeck, B., Luu, M., et al. (2022). Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells. EMBO Rep 23, e54685. 10.15252/embr.202254685.
[32] Lv, J., Qi, P., Yan, X., Bai, L., and Zhang, L. (2023). Structure and Metabolic Characteristics of Intestinal Microbiota in Tibetan and Han Populations of Qinghai-Tibet Plateau and Associated Influencing Factors. Microorganisms 11. 10.3390/microorganisms11112655.
[33] Zhang, X., Xu, W., Zhong, W., Zhang, W., Yang, C., Duan, L., Niu, H., Dong, Y., Liu, T., Xia, S., and Wang, B. (2023). Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau. J Zhejiang Univ Sci B 24, 823-838. 10.1631/jzus.B2200509.
[34] Jia, Z., Zhao, X., Liu, X., Zhao, L., Jia, Q., Shi, J., Xu, X., Hao, L., Xu, Z., Zhong, Q., et al. (2020). Impacts of the Plateau Environment on the Gut Microbiota and Blood Clinical Indexes in Han and Tibetan Individuals. mSystems 5. 10.1128/mSystems.00660-19. 
[35] Wang, J., Chen, Y., Zhong, H., Chen, F., Regenstein, J., Hu, X., Cai, L., and Feng, F. (2022). The gut microbiota as a target to control hyperuricemia pathogenesis: Potential mechanisms and therapeutic strategies. Crit Rev Food Sci Nutr 62, 3979-3989. 10.1080/10408398.2021.1874287. 
[36] Hussain, A., Rui, B., Ullah, H., Dai, P., Ahmad, K., Yuan, J., Liu, Y., and Li, M. (2024). Limosilactobacillus reuteri HCS02-001 Attenuates Hyperuricemia through Gut Microbiota-Dependent Regulation of Uric Acid Biosynthesis and Excretion. Microorganisms 12. 10.3390/microorganisms12040637.
[37] Ni, C., Li, X., Wang, L., Li, X., Zhao, J., Zhang, H., Wang, G., and Chen, W. (2021). Lactic acid bacteria strains relieve hyperuricaemia by suppressing xanthine oxidase activity via a short-chain fatty acid-dependent mechanism. Food Funct 12, 7054-7067. 10.1039/d1fo00198a.
[38] Shen, Y., Wang, Y., Chang, C., Li, S., Li, W., and Ni, B. (2019). Prevalence and risk factors associated with hyperuricemia among working population at high altitudes: a cross-sectional study in Western China. Clin Rheumatol 38, 1375-1384. 10.1007/s10067-018-4391-9.
[39] Du, Y., Qi, M., Wang, W., and Chen, B. (2022). Effect of High-altitude Hypoxia Environment on Uric Acid Excretion, Desmin Protein Level in Podocytes, and Na+-K+- ATPase Activity. Cell Mol Biol (Noisy-le-grand) 68, 84-91. 10.14715/cmb/2022.68.6.14.
[40] Hu, H., Li, W., Hao, Y., Peng, Z., Zou, Z., Wei, J., Zhou, Y., Liang, W., and Cao, Y. (2024). The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy. Cell Rep Med 5, 101690. 10.1016/j.xcrm.2024.101690. 
[41] Liu, L., Zhao, T., Shan, L., Cao, L., Zhu, X., and Xue, Y. (2021). Estradiol regulates intestinal ABCG2 to promote urate excretion via the PI3K/Akt pathway. Nutr Metab (Lond) 18, 63. 10.1186/s12986-021-00583-y.
[42] Jung, J.H., Song, G.G., Lee, Y.H., Kim, J.H., Hyun, M.H., and Choi, S.J. (2018). Serum uric acid levels and hormone therapy type: a retrospective cohort study of postmenopausal women. Menopause 25, 77-81. 10.1097/gme.0000000000000953.
[43] Wan, H., Zhang, K., Wang, Y., Chen, Y., Zhang, W., Xia, F., Zhang, Y., Wang, N., and Lu, Y. (2020). The Associations between Gonadal Hormones and Serum Uric Acid Levels in Men and Postmenopausal Women with Diabetes. Front Endocrinol (Lausanne) 11, 55. 10.3389/fendo.2020.00055.
[44] Jiang, Y. M., Qiu, K. L., & Liao, Y. F. (2024). Research progress on the relationship between sex hormones, sex hormone-binding globulin, and hyperuricemia/gout. Journal of Huazhong University of Science and Technology (Medical Sciences), 53(3), 389-393.

Subscription
E-Mail Alert
Most popular papers
Call for Special Issue
Publication Ethics & OA Statement
Plagiarism Policy
Contact Us
Downloads: 9214
Visits: 555890

Sponsors, Associates, and Links

All published work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright © 2016 - 2031 Clausius Scientific Press Inc. All Rights Reserved.