维持性血液透析患者高磷血症促动脉粥样硬化的机制及降磷治疗研究进展
Mechanisms of Arteriosclerosis Induced by Hyperphosphatemia in Maintenance Hemodialysis Patients and Research Progress of Phosphorus-Lowering Therapy
摘要: 高磷血症是慢性肾脏病(CKD)尤其是晚期血液透析患者常见的并发症,而高磷与动脉粥样硬化性心血管疾病(ASCVD)的发生发展密切相关。高磷血症可抑制内皮型一氧化氮合酶(eNOS)活性,导致内皮功能障碍;激活炎症小体,释放促炎因子,加剧血管炎症;扰乱胆固醇稳态,促进泡沫细胞形成。降磷治疗是改善CKD患者心血管预后的重要手段,非含钙磷结合剂在降低血磷的同时,部分研究表明,还可显著减少心血管事件和全因死亡率。本文综述了高磷血症促进动脉粥样硬化的机制,降磷药物的研究现状及减少CKD患者动脉粥样硬化发生率的机制,为维持性血液透析高磷血症患者心血管疾病防治提供理论依据。
Abstract: Hyperphosphatemia is a common complication in patients with chronic kidney disease (CKD), especially those undergoing hemodialysis in advanced stages. It is closely associated with the occurrence and progression of atherosclerotic cardiovascular disease (ASCVD). Hyperphosphatemia can inhibit the activity of endothelial nitric oxide synthase (eNOS), leading to endothelial dysfunction; activate inflammasomes, release pro-inflammatory factors, and exacerbate vascular inflammation; disrupt cholesterol homeostasis and promote foam cell formation. Phosphorus-lowering therapy is an important approach to improve the cardiovascular prognosis of CKD patients. Non-calcium-based phosphate binders not only reduce serum phosphorus levels but also significantly decrease cardiovascular events and all-cause mortality. This article reviews the mechanisms by which hyperphosphatemia promotes atherosclerosis, the current research status of phosphorus-lowering drugs, and the mechanisms underlying the reduction of atherosclerosis incidence in CKD patients, providing a theoretical basis for the prevention and treatment of cardiovascular diseases in maintenance hemodialysis patients with hyperphosphatemia.
文章引用:焦欣宇, 欧阳南. 维持性血液透析患者高磷血症促动脉粥样硬化的机制及降磷治疗研究进展[J]. 临床个性化医学, 2026, 5(1): 546-552. https://doi.org/10.12677/jcpm.2026.51075

参考文献

[1] Li, Y., Ning, Y., Shen, B., Shi, Y., Song, N., Fang, Y., et al. (2022) Temporal Trends in Prevalence and Mortality for Chronic Kidney Disease in China from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019. Clinical Kidney Journal, 16, 312-321. [Google Scholar] [CrossRef] [PubMed]
[2] Jankowski, J., Floege, J., Fliser, D., Böhm, M. and Marx, N. (2021) Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options. Circulation, 143, 1157-1172. [Google Scholar] [CrossRef] [PubMed]
[3] Global Burden of Disease Study 2017 Collaborators (2020) Global, Regional, and National Burden of Chronic Kidney Disease, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017. The Lancet, 395, 662-664.
[4] Rahman, M., Xie, D., Feldman, H.I., Go, A.S., He, J., Kusek, J.W., et al. (2014) Association between Chronic Kidney Disease Progression and Cardiovascular Disease: Results from the CRIC Study. American Journal of Nephrology, 40, 399-407. [Google Scholar] [CrossRef] [PubMed]
[5] Li, Y., Cui, R., Liu, K., Eshak, E.S., Cui, M., Dong, J., et al. (2021) Relationship between Endothelial Dysfunction and Prevalence of Chronic Kidney Disease: The Circulatory Risk in Communities Study (CIRCS). Journal of Atherosclerosis and Thrombosis, 28, 622-629. [Google Scholar] [CrossRef] [PubMed]
[6] Shah, A., et al. (2024) Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD). StatPearls.
[7] Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group (2017) KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney International Supplements, 7, 1-59.
[8] Vervloet, M.G. and van Ballegooijen, A.J. (2018) Prevention and Treatment of Hyperphosphatemia in Chronic Kidney Disease. Kidney International, 93, 1060-1072. [Google Scholar] [CrossRef] [PubMed]
[9] Foley, R.N., Collins, A.J., Herzog, C.A., Ishani, A. and Kalra, P.A. (2009) Serum Phosphorus Levels Associate with Coronary Atherosclerosis in Young Adults. Journal of the American Society of Nephrology, 20, 397-404. [Google Scholar] [CrossRef] [PubMed]
[10] Dhingra, R., Sullivan, L.M., Fox, C.S., et al. (2007) Relations of Serum Phosphorus and Calcium Levels to the Incidence of Cardiovascular Disease in the Community. Archives of Internal Medicine, 167, Article 879. [Google Scholar] [CrossRef] [PubMed]
[11] Jamal, S.A., Fitchett, D., Lok, C.E., Mendelssohn, D.C. and Tsuyuki, R.T. (2009) The Effects of Calcium-Based versus Non-Calcium-Based Phosphate Binders on Mortality among Patients with Chronic Kidney Disease: A Meta-Analysis. Nephrology Dialysis Transplantation, 24, 3168-3174. [Google Scholar] [CrossRef] [PubMed]
[12] Mason, D.L., Godugu, K., Nnani, D. and Mousa, S.A. (2022) Effects of Sevelamer Carbonate versus Calcium Acetate on Vascular Calcification, Inflammation, and Endothelial Dysfunction in Chronic Kidney Disease. Clinical and Translational Science, 15, 353-360. [Google Scholar] [CrossRef] [PubMed]
[13] Xu, J., Zeng, R., Liao, P. and Zhang, M. (2021) Effect of Lanthanum Carbonate on the Progression of Coronary Artery Calcification in Hemodialysis Patients: A Meta‐Analysis of Randomized Controlled Trials. Hemodialysis International, 26, 223-233. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, P.X., et al. (2022) Effect of Calcium-Based Phosphate Binders Versus Sevelamer on Mortality of Patients with Hemodialysis: A Meta-Analysis. Iranian Journal of Kidney Diseases, 16, 215-227.
[15] Gusev, E. and Sarapultsev, A. (2023) Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes. International Journal of Molecular Sciences, 24, Article 7910. [Google Scholar] [CrossRef] [PubMed]
[16] Bolignano, D., Greco, M., Arcidiacono, V., Presta, P., Caglioti, A., Andreucci, M., et al. (2022) Circulating Omentin-1, Sustained Inflammation and Hyperphosphatemia at the Interface of Subclinical Atherosclerosis in Chronic Kidney Disease Patients on Chronic Renal Replacement Therapy. Medicina, 58, Article 890. [Google Scholar] [CrossRef] [PubMed]
[17] Shuto, E., Taketani, Y., Tanaka, R., Harada, N., Isshiki, M., Sato, M., et al. (2009) Dietary Phosphorus Acutely Impairs Endothelial Function. Journal of the American Society of Nephrology, 20, 1504-1512. [Google Scholar] [CrossRef] [PubMed]
[18] Stevens, K.K., Patel, R.K., Mark, P.B., Delles, C. and Jardine, A.G. (2015) Phosphate as a Cardiovascular Risk Factor: Effects on Vascular and Endothelial Function. The Lancet, 385, S10. [Google Scholar] [CrossRef] [PubMed]
[19] Czaya, B., Heitman, K., Campos, I., Yanucil, C., Kentrup, D., Westbrook, D., et al. (2022) Hyperphosphatemia Increases Inflammation to Exacerbate Anemia and Skeletal Muscle Wasting Independently of FGF23-FGFR4 Signaling. eLife, 11, e74782. [Google Scholar] [CrossRef] [PubMed]
[20] Zhao, M., Xu, M., Cai, Y., Zhao, G., Guan, Y., Kong, W., et al. (2011) Mitochondrial Reactive Oxygen Species Promote P65 Nuclear Translocation Mediating High-Phosphate-Induced Vascular Calcification in Vitro and in Vivo. Kidney International, 79, 1071-1079. [Google Scholar] [CrossRef] [PubMed]
[21] Czaya, B., Faul, C., Kirsch, A., et al. (2020). FGF23-FGFR4 Signaling Is Dispensable for Hyperphosphatemia-Induced Inflammation and Hypoferremia in Chronic Kidney Disease. JCI Insight, 5(4), e132345.[CrossRef
[22] Jiang, H., et al. (2022) Role of Endothelial Cells in Vascular Calcification. Frontiers in Cardiovascular Medicine, 9, 895005. [Google Scholar] [CrossRef] [PubMed]
[23] Mironov, N., Atfi, A. and Razzaque, M.S. (2022) Phosphate Burden and Organ Dysfunction. Frontiers in Aging, 3, Article ID: 890985. [Google Scholar] [CrossRef] [PubMed]
[24] Ellam, T.J. and Chico, T.J.A. (2012) Phosphate: The New Cholesterol? The Role of the Phosphate Axis in Non-Uremic Vascular Disease. Atherosclerosis, 220, 310-318. [Google Scholar] [CrossRef] [PubMed]
[25] Tanaka, S., Yamamoto, H., Nakahashi, O., Kagawa, T., Ishiguro, M., Masuda, M., et al. (2013) Dietary Phosphate Restriction Induces Hepatic Lipid Accumulation through Dysregulation of Cholesterol Metabolism in Mice. Nutrition Research, 33, 586-593. [Google Scholar] [CrossRef] [PubMed]
[26] Zhou, C., He, Q., Gan, H., Zeng, T., Liu, Q., Moorhead, J.F., et al. (2021) Hyperphosphatemia in Chronic Kidney Disease Exacerbates Atherosclerosis via a Mannosidases-Mediated Complex-Type Conversion of SCAP N-glycans. Kidney International, 99, 1342-1353. [Google Scholar] [CrossRef] [PubMed]
[27] Yamada, S. and Nakano, T. (2023) Role of Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (MBD) in the Pathogenesis of Cardiovascular Disease in CKD. Journal of Atherosclerosis and Thrombosis, 30, 835-850. [Google Scholar] [CrossRef
[28] Zoccali, C. (2006) Traditional and Emerging Cardiovascular and Renal Risk Factors: An Epidemiologic Perspective. Kidney International, 70, 26-33. [Google Scholar] [CrossRef] [PubMed]
[29] Cernaro, V., Longhitano, E., Calabrese, V., Casuscelli, C., Di Carlo, S., Spinella, C., et al. (2023) Progress in Pharmacotherapy for the Treatment of Hyperphosphatemia in Renal Failure. Expert Opinion on Pharmacotherapy, 24, 1737-1746. [Google Scholar] [CrossRef] [PubMed]
[30] Zeng, Q., Zhong, Y. and Yu, X. (2023) Meta-Analysis of the Efficacy and Safety of Sevelamer as Hyperphosphatemia Therapy for Hemodialysis Patients. Renal Failure, 45, Article 2210230. [Google Scholar] [CrossRef] [PubMed]
[31] Floege, J. (2020) Phosphate Binders in Chronic Kidney Disease: An Updated Narrative Review of Recent Data. Journal of Nephrology, 33, 497-508. [Google Scholar] [CrossRef] [PubMed]
[32] Ogata, H., Takeshima, A. and Ito, H. (2022) An Update on Phosphate Binders for the Treatment of Hyperphosphatemia in Chronic Kidney Disease Patients on Dialysis: A Review of Safety Profiles. Expert Opinion on Drug Safety, 21, 947-955. [Google Scholar] [CrossRef] [PubMed]
[33] Hill Gallant, K.M., Sprague, S.M., Rosenbaum, D.P., Spiegel, D.M., Kozuka, K., Edelstein, S., et al. (2025) Tenapanor: A Phosphate Absorption Inhibitor for the Management of Hyperphosphatemia in Patients with Kidney Failure. Journal of Renal Nutrition, 35, 25-34. [Google Scholar] [CrossRef] [PubMed]
[34] Siasos, G., Tousoulis, D., Michalea, S., Oikonomou, E., Kolia, C., Kioufis, S., et al. (2012) Biomarkers Determining Cardiovascular Risk in Patients with Kidney Disease. Current Medicinal Chemistry, 19, 2555-2571. [Google Scholar] [CrossRef] [PubMed]
[35] Jovanovich, A., Struemph, T., You, Z., Wang, W., Farmer-Bailey, H., Bispham, N., et al. (2024) Effect of Lanthanum Carbonate on Serum Phosphate, Oxidative Stress, and Vascular Dysfunction in CKD. Kidney360, 5, 959-966. [Google Scholar] [CrossRef] [PubMed]
[36] Chaiyakittisopon, K., Pattanaprateep, O., Ponthongmak, W., Kunakorntham, P., Chuasuwan, A., Ingsathit, A., et al. (2025) Effectiveness of Phosphate Binders on Mortality and Cardiovascular Disease in End-Stage Renal Disease Patients with Hyperphosphatemia: A Multicenter Real-World Cohort Study. BMC Nephrology, 26, Article No. 131. [Google Scholar] [CrossRef] [PubMed]
[37] Rocha‐Singh, K.J., Zeller, T. and Jaff, M.R. (2014) Peripheral Arterial Calcification: Prevalence, Mechanism, Detection, and Clinical Implications. Catheterization and Cardiovascular Interventions, 83, E212-E220. [Google Scholar] [CrossRef] [PubMed]
[38] Ogata, H., Sugawara, H., Yamamoto, M. and Ito, H. (2024) Phosphate and Coronary Artery Disease in Patients with Chronic Kidney Disease. Journal of Atherosclerosis and Thrombosis, 31, 1-14. [Google Scholar] [CrossRef] [PubMed]
[39] Kutikhin, A.G., Feenstra, L., Kostyunin, A.E., Yuzhalin, A.E., Hillebrands, J. and Krenning, G. (2021) Calciprotein Particles. Arteriosclerosis, Thrombosis, and Vascular Biology, 41, 1607-1624. [Google Scholar] [CrossRef] [PubMed]