【摘要】目的探讨维持性血液透析(maintenance hemodialysis patients,MHD)患者血清成纤维细胞生长因子-23(fibroblast growth factor-23,FGF-23)及可溶性klotho 蛋白(soluble Klotho protein,sKL)与心脏瓣膜钙化(cardiac valve calcification,CVC)的关系。方法收集山东第一医科大学附属莱钢医院肾内科透析中心100 例维持性血液透析患者的临床资料。采用酶联免疫吸附法测定患者血清FGF-23 和sKL 浓度,超声心动图评估患者心脏瓣膜钙化情况。结果观察组的CVC 比例、FGF-23水平高于对照组,而sKL 水平低于对照组(t 值分别为8.820, 16.642, - 2.583, P 值分别为<0.001,<0.001, 0.012)。多因素Logistic 回归分析显示,血清FGF-23 水平、血磷升高是MHD 患者心脏瓣膜钙化的独立危险因素(OR 值分别为2.375,1.642,95%CI 值分别为1.527~3.884,1.232~1.912,P 值分别为<0.001, 0.023),血清sKL 水平升高是MHD 患者心脏瓣膜钙化的保护因素(OR=0.334, 95%CI 值为0.044~0.621, P=0.032)。结论血清FGF-23、sKL 是MHD 患者发生心脏瓣膜钙化的独立影响因素,二者联合检测对MHD患者发生心脏瓣膜钙化具有较高的预测价值。
【Abstract】Objective To explore the relationship between serum levels of fibroblast growth factor- 23(FGF- 23) and soluble klotho (sKL) and cardiac valve calcification (CVC) in maintenance hemodialysis (MHD) patients. Methods A total of 100 MHD patients treated in the Blood Purification Center of Laigang Hospital were enrolled in this study as the observation group. The serum concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assay. CVC was detected by color Doppler ultrasonography. Results The incidence of CVC and serum level of FGF-23 were higher in observation group than in control group (t=8.820 and 16.642 respectively; P<0.001), while serum level of sKL was lower in observation group than in control group (t= -2.583, P=0.012). The higher levels of serum phosphorus and serum FGF-23 were the independent risk factors for CVC in MHD patients (OR = 2.375 and 1.642 respectively; 95% CI = 1.527 ~ 3.884 and 1.232 ~ 1.912 respectively; P<0.001 and 0.023 respectively). The higher level of sKL was a protective factor for CVC (OR=0.334, 95% CI=0.044~0.621, P<0.05). Conclusion Serum levels of FGF-23 and sKL were the independent influencing factors for CVC in MHD patients. Therefore, combined detection
of serum FGF-23 and sKL can be used to predict CVC in MHD patients.
1 Drew, D. A. et al. Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition Study. J Am Soc Nephrol 28, 1859-1866, doi:10.1681/ASN.2016080828 (2017).
2 Navarro-Gonzalez, J. F. et al. Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease. Diabetes Care 41, 1817-1820, doi:10.2337/dc18-0078 (2018).
3 Kobayashi, S. Cardiovascular Events in Hemodialysis Patients: Challenging against Vascular Calcification. Ann Vasc Dis 10, 1-7, doi:10.3400/avd.ra.17-00006 (2017).
4 Choi, H. M., Kwon, Y. E., Kim, S. & Oh, D. J. Changes in FGF-23, Neutrophil/Platelet Activation Markers, and Angiogenin in Advanced Chronic Kidney Disease and Their Effect on Arterial Stiffness. Kidney Blood Press Res 44, 1166-1178, doi:10.1159/000502526 (2019).
5 Gu, Y., Ren, K., Wang, L. & Yao, Q. Loss of Klotho contributes to cartilage damage by derepression of canonical Wnt/beta-catenin signaling in osteoarthritis mice. Aging (Albany NY) 11, 12793-12809, doi:10.18632/aging.102603 (2019).
6 Minisola, S., Colangelo, L., Cipriani, C. & Pepe, J. FGF 23 and trabecular microarchitecture. Osteoporos Int 30, 2357, doi:10.1007/s00198-019-05123-2 (2019).
7 Zou, X. R. et al. Influence of the Klotho/FGF23/Egr1 signaling pathway on calcium-phosphorus metabolism in diabetic nephropathy and the intervention of Shenyuan granules. J Biol Regul Homeost Agents 33, 1695-1702, doi:10.23812/19-207-A (2019).
8 Brandenburg, V. M., Schuh, A. & Kramann, R. Valvular Calcification in Chronic Kidney Disease. Adv Chronic Kidney Dis 26, 464-471, doi:10.1053/j.ackd.2019.10.004 (2019).
9 Kidney Disease: Improving Global Outcomes, C. K. D. M. B. D. W. G. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl, S1-130, doi:10.1038/ki.2009.188 (2009).
10 Tian, Y. et al. Risk Factors for New-Onset Cardiac Valve Calcification in Patients on Maintenance Peritoneal Dialysis. Cardiorenal Med 6, 150-158, doi:10.1159/000443620 (2016).
11 Avila-Diaz, M. et al. De novo development of heart valve calcification in incident peritoneal dialysis patients. Arch Med Res 44, 638-644, doi:10.1016/j.arcmed.2013.10.015 (2013).
12 Wang, C. et al. Risk factor analysis of calcification in aortic and mitral valves in maintenance peritoneal dialysis patients. Kidney Blood Press Res 37, 488-495, doi:10.1159/000355729 (2013).
13 Zapolski, T. Malnutrition-inflammation complex syndrome: link between end-stage renal disease, atherosclerosis and valvular calcification. Hypertens Res 33, 541-543, doi:10.1038/hr.2010.50 (2010).
14 Gallieni, M. et al. Prevalence and progression of cardiovascular calcifications in peritoneal dialysis patients: A prospective study. Bone 51, 332-337, doi:10.1016/j.bone.2012.06.002 (2012).
15 Ding, H. Y. & Ma, H. X. Significant roles of anti-aging protein klotho and fibroblast growth factor23 in cardiovascular disease. J Geriatr Cardiol 12, 439-447, doi:10.11909/j.issn.1671-5411.2015.04.017 (2015).
16 John, G. B., Cheng, C. Y. & Kuro-o, M. Role of Klotho in aging, phosphate metabolism, and CKD. Am J Kidney Dis 58, 127-134, doi:10.1053/j.ajkd.2010.12.027 (2011).