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临床研究

血清成纤维细胞生长因子21与腹膜透析患者不同部位血管钙化的相关性研究

  • 张圆圆 ,
  • 刘天驰 ,
  • 陈香吟 ,
  • 曹婧媛 ,
  • 杨艳 ,
  • 卢国元 ,
  • 赵诗竹
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  • 215000 苏州,1苏州大学附属第一医院肾内科
    210000 南京,2东南大学医学院
    213000 常州,3常州市第一人民医院肾内科
    225300 泰州,4泰州市人民医院肾内科

收稿日期: 2024-08-19

  修回日期: 2025-05-12

  网络出版日期: 2025-08-12

基金资助


Correlation between serum fibroblast growth factor 21 and vascular calcification in different parts of peritoneal dialysis patients

  • ZHANG Yuan-Yuan ,
  • LIU Tian-Chi ,
  • CHEN Xiang-Yin ,
  • CAO Jing-Yuan ,
  • YANG Yan ,
  • LU Guo-Yuan ,
  • ZHAO Shi-Zhu
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  • Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China; 2School of Medicine, Southeast University, Nanjing 210000, China; 3Department of Nephrology, The First People’s Hospital of Changzhou, Changzhou 213000, China; 4Department of Nephrology, Taizhou People’s Hospital, Taizhou 225300, China

Received date: 2024-08-19

  Revised date: 2025-05-12

  Online published: 2025-08-12

摘要

目的 血管钙化与腹膜透析(peritoneal dialysis,PD)患者心血管疾病发生密切相关。成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)作为一种内分泌激素对心血管具有保护作用。本研究探究了PD患者血清FGF21与不同部位血管钙化的相关性。 方法 纳入2021年8月─2022年10月于苏州大学附属第一医院肾内科行腹膜透析充分性评估的PD患者,将其作为PD组,纳入同期于苏州大学附属第一医院体检的健康人群作为对照组。测定血清FGF21、FGF23水平。使用GE工作站处理PD组患者的胸腹部平扫CT,定量评估冠状动脉钙化(coronary artery calcification,CAC)及腹主动脉钙化(abdominal artery calcification,AAC)的体积。按照钙化发生与否进行分组,使用多因素Logistic回归分析FGF21与CAC及AAC的发生是否具有相关性。 结果 共纳入PD组患者136例,对照组20例,PD组患者血清FGF21高于对照组(Z=5.087,P<0.001)。随着年龄的增长(r=0.247,P=0.004)、透析龄的延长(r=0.306,P<0.001),PD组患者血清FGF21逐渐升高,血清FGF21水平与CAC体积(r=0.254,P=0.005)及AAC体积(r=0.354,P<0.001)呈正相关。不同部位血管钙化危险因素不同,FGF21升高与PD组患者AAC发生风险增加独立相关(OR=1.783,95% CI:1.251~2.541,P=0.001),而与CAC发生与否无关联。 结论 PD组患者血清FGF21较正常人显著升高,且FGF21增加与AAC发生风险增加有关。未来,FGF21可能作为血管钙化的生物标志物及潜在治疗靶点。

本文引用格式

张圆圆 , 刘天驰 , 陈香吟 , 曹婧媛 , 杨艳 , 卢国元 , 赵诗竹 . 血清成纤维细胞生长因子21与腹膜透析患者不同部位血管钙化的相关性研究[J]. 中国血液净化, 2025 , 24(08) : 653 -658 . DOI: 10.3969/j.issn.1671-4091.2025.08.007

Abstract

Objective  Vascular calcification is closely related to cardiovascular disease in patients with peritoneal dialysis (PD). Fibroblast growth factor 21 (FGF21) as an endocrine hormone has a protective effect on cardiovascular function. This study explored the correlation between serum FGF21 and vascular calcification in different parts of vessels in PD patients.  Methods  PD patients who were evaluated for adequacy of PD in the Department of Nephrology, The First Affiliated Hospital of Soochow University from August 2021 to October 2022 were included in this study. Healthy people who underwent physical examination during the same period were recruited as the controls. Fasting blood serum was collected from all subjects, and serum FGF21 and FGF23 levels were determined by enzyme-linked immunoassay. Chest and abdomen CT were conducted in PD patients and processed by the GE workstation. Volume of coronary artery calcification (CAC) and abdominal aortic calcification (AAC) was quantitatively assessed. PD patients were grouped according to the presence of CAC or AAC. Multivariate logistic regression was used to analyze the relationship between serum FGF21 level and the presence of CAC or AAC.  Results  A total of 136 PD patients and 20 healthy controls were included in this study. Serum FGF21 in PD patients was significantly higher than that in normal subjects [383.0 (110.3~767.9) vs. 13.3 (5.5~129.1) pg/mL, Z=5.087, P<0.001]. With the increase of age (r=0.247, P=0.004) and dialysis vintage (r=0.306, P<0.001), serum FGF21 in PD patients was gradually increased. FGF21 was positively correlated with CAC volume (r=0.254, P=0.005) and AAC volume (r=0.354, P<0.001). Furthermore, there were different risk factors for CAC and AAC. The increase of FGF21 was independently associated with the increased risk of AAC (OR=1.783, 95% CI: 1.251~2.541, P=0.001) rather than CAC in PD patients.  Conclusions  Serum FGF21 in PD patients is significantly higher than that in healthy people. The increase of FGF21 is associated with an increased risk of AAC. Therefore, FGF21 may serve as a biomarker and potential therapeutic target for vascular calcification.

参考文献

[1]. Cozzolino M, Mangano M, Stucchi A, et al. Cardiovascular disease in dialysis patients[J]. Nephrol Dial Transplant, 2018, 33(suppl_3): i28-i34.
[2]. Dialysis China CS, Yu XQ, Yang JW, et al. Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis: baseline results from a prospective cohort study[J]. Curr Med Res Opin, 2018, 34(8): 1491-1500.
[3]. Sorensen I, Saurbrey S, Hjortkjaer HO, et al. Regional distribution and severity of arterial calcification in patients with chronic kidney disease stages 1-5: a cross-sectional study of the Copenhagen chronic kidney disease cohort[J]. BMC Nephrol, 2020, 21(1): 534.
[4]. Zhang H, Li G, Yu X, et al. Progression of Vascular Calcification and Clinical Outcomes in Patients Receiving Maintenance Dialysis[J]. JAMA Netw Open, 2023, 6(5): e2310909.
[5.] Kaur R, Singh R. Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications[J]. Life Sci, 2022, 311(Pt B): 121148.
[6]. Kondo Y, Komaba H, Fukagawa M. Endocrine fibroblast growth factors as potential biomarkers for chronic kidney disease[J]. Expert Rev Mol Diagn, 2020, 20(7): 715-724.
[7]. Lewis JE, Ebling FJP, Samms RJ, et al. Going Back to the Biology of FGF21: New Insights[J]. Trends in Endocrinology & Metabolism, 2019, 30(8): 491-504.
[8]. Cao F, Wang S, Cao X, et al. Fibroblast growth factor 21 attenuates calcification of vascular smooth muscle cells in vitro[J]. J Pharm Pharmacol, 2017, 69(12): 1802-1816.
[9]. Liu C, Sch?nke M, Zhou E, et al. Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis[J]. Cardiovasc Res, 2021, 2(118): 489-502.
[10]. Wu L, Qian L, Zhang L,et al. Fibroblast Growth Factor 21 is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Atherosclerotic Cardiovascular Events[J]. J Am Heart Assoc, 2020, 9(11): e15226.
[11]. He Y, Li Y, Wei Z, et al. Pharmacokinetics, tissue distribution, and excretion of FGF-21 following subcutaneous administration in rats[J]. Drug Test Anal, 2018, doi:10.1002/dta.2365(257): 259-265.
[12]. Zhang R, Li Y, Zhou X, et al. Association of serum fibroblast growth factor 21 with kidney function in a population-based Chinese cohort[J]. Medicine, 2021, 100(50): e28238.
[13]. Anuwatmatee S, Allison MA, Shlipak MG, et al. Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis[J]. Nephrol Dial Transplant, 2019, 34(6): 1009-1016.
[14]. Stein S, Bachmann A, Lossner U, et al. Serum levels of the adipokine FGF21 depend on renal function[J]. Diabetes Care, 2009, 32(1): 126-128.
[15]. Han SH, Choi SH, Cho BJ, et al. Serum fibroblast growth factor-21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis[J]. Metabolism, 2010, 59(11): 1656-1662.
[16]. González E, Díez JJ, Bajo MA, et al. Fibroblast Growth Factor 21 (FGF-21) in Peritoneal Dialysis Patients: Natural History and Metabolic Implications[J]. Plos One, 2016, 11(3): e151698.
[17]. Lin Z, Pan X, Wu F, et al. Fibroblast Growth Factor 21 Prevents Atherosclerosis by Suppression of Hepatic Sterol Regulatory Element-Binding Protein-2 and Induction of Adiponectin in Mice[J]. Circulation, 2015, 131(21): 1861-1871.
[18]. Shi Y, Wang S, Peng H, et al. Fibroblast Growth Factor 21 Attenuates Vascular Calcification by Alleviating Endoplasmic Reticulum Stress Mediated Apoptosis in Rats[J]. Int J Biol Sci, 2019, 15(1): 138-147.
[19]. Jiang L, Yin Q, Yang M, et al. Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients[J]. Kidney diseases, 2021, 7(3): 227-240.
[20]. Chiu LT, Hung CD, Lin L, et al. Serum Fibroblast Growth Factor 21 Level Is Associated with Aortic Stiffness in Patients on Maintenance Hemodialysis[J]. Int J Hypertens, 2022, doi:10.1155/2022/7098458(2022): 7098458.
[21]. Matsui M, Kosaki K, Kuro-O M, Set al. Circulating fibroblast growth factor 21 links hemodynamics with kidney function in middle-aged and older adults: A mediation analysis[J]. Hypertens Res, 2022, 45(1): 125-134.
[22]. Shi Y, Lu W, Hou Y, et al. Fibroblast growth factor 21 ameliorates vascular calcification by inhibiting osteogenic transition in vitamin D3 plus nicotine-treated rats[J]. Biochem Biophys Res Commun, 2018, 495(4): 2448-2455.
[23]. Kokkinos J, Tang S, Rye K, et al. The role of fibroblast growth factor 21 in atherosclerosis[J]. Atherosclerosis, 2017, 257(doi:10.1016/j.atherosclerosis.2016.11.033): 259-265.
[24]. Schlieper G. Vascular calcification in chronic kidney disease: not all arteries are created equal[J]. Kidney Int, 2014, 85(3): 501-503.
[25]. Niu Q, Zhao H, Wu B, et al. Study on the Prevalence of Vascular Calcification in Different Types of Arteries and Influencing Factors in Maintenance Peritoneal Dialysis Patients[J]. Blood Purificat, 2019, 47(Suppl. 1): 8-16.
[26]. Fon TK, Bookout AL, Ding X,et al. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse[J]. Mol Endocrinol, 2010, 24(10): 2050-2064.
[27]. Gomel MA, Lee R, Grande-Allen KJ. Comparing the Role of Mechanical Forces in Vascular and Valvular Calcification Progression[J]. Front Cardiovasc Med, 2018, 197(5): 10-3389.
[28]. Sayanthan S, Allison MA, Budoff MJ, et al. Relationship of fibroblast growth factor 21 with the prevalence and progression of vascular and valvular calcification: Multi-ethnic study of atherosclerosis[J]. Int J Cardiol, 2023, doi:10.1016/j.ijcard.2022.10.145(370): 388-395.
[29]. Ong KL, Campbell S, Wu BJ, et al. Relationship of fibroblast growth factor 21 with subclinical atherosclerosis and cardiovascular events: Multi-Ethnic Study of Atherosclerosis[J]. Atherosclerosis, 2019, doi:10.1016/j.atherosclerosis.2019.06.898(287): 46-53.
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