Department of Medicine, Tokyo Women's Medical University Medical Center, East Tokyo 2-1-10, Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan.
Department of Nephrology, Heisei-Hidaka Clinic, Takasaki, Gunma, Japan.
Heart Vessels. 2021 Mar;36(3):414-423. doi: 10.1007/s00380-020-01704-y. Epub 2020 Sep 30.
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. High circulating FGF23 levels are associated with increased mortality in patients with chronic kidney disease and those on dialysis. Current data also suggest higher circulating levels of FGF23 are associated with cardiovascular mortality, vascular calcification, and left ventricular hypertrophy; however, evidence on the role of FGF23 in patients on dialysis is incomplete, and some of the data, especially those on cardiovascular disease (CVD), are controversial. This study aimed to evaluate factors associated with FGF23 in hemodialysis patients with or without CVD. Randomly selected 76 patients on maintenance hemodialysis at a single hemodialysis center were enrolled. After the exclusion of eight patients with extremely outlying FGF23 levels, 68 patients, including 48 males and 46 patients with a CVD history, were included in the study. The mean age was 64.4 ± 12.1 years, and the mean dialysis duration was 12.7 ± 7.1 years. Dialysis duration, time-averaged concentration of urea (TAC-urea), ultrafiltration rate (UFR), blood pressure during hemodialysis session, laboratory data, and echocardiographic parameters including interventricular septum thickness (IVST), left ventricular mass indices (LVMI), and ejection fraction were included in univariate and multivariate analyses. The median lgFGF23 levels in the overall cohort and in those with and without CVD were 2.14 (interquartile range, IQR - 0.43 to - 4.23), 2.01 (- 0.52 to 4.12), and 2.59 (0.07 to 4.32), respectively, and there was no difference between the patients with and without CVD (p = 0.14). The univariate analysis revealed that FGF23 was significantly associated with age (r = - 0.12, p < 0.01), duration of hemodialysis (r = - 0.11, p < 0.01), TAC-urea (r = 0.29, p = 0.01), UFR (r = 0.26, p = 0.04), alkaline phosphatase (ALP; r = - 0.27, p = 0.03), corrected serum calcium (cCa; r = 0.32, p < 0.01), serum phosphate (iP, r = 0.57, p < 0.01), intact parathyroid hormone (iPTH; r = 0.38, p < 0.01), IVST (r = 0.30, p = 0.01), and LVMI (r = 0.26, p = 0.04). In multivariate regression analysis, FGF23 was significantly associated with cCa (F = 25.6, p < 0.01), iP (F = 22.5, p < 0.01), iPTH (F = 19.2, p < 0.01), ALP (F = 5.34, p = 0.03), and UFR (F = 3.94, p = 0.05). In addition, the univariate analysis after the categorization of patients according to CVD indicated that FGF23 was significantly associated with cCa (r = 0.34, p = 0.02), iP (r = 0.41, p < 0.01), iPTH (r = 0.39, p = 0.01), and TAC-urea (r = 0.45, p < 0.01) in patients with CVD, whereas only IVST (r = 0.53, p = 0.04) was associated with FGF23 in those without CVD. FGF23 levels in hemodialysis patients were extremely high and associated not only with mineral bone disease-related factors but also with UFR. Additionally, dialysis efficacy might be associated with lower FGF23 levels in patients with CVD.
成纤维细胞生长因子 23(FGF23)是一种骨源性激素,可调节肾脏近端小管中的磷重吸收和维生素 D 合成。高循环 FGF23 水平与慢性肾脏病患者和透析患者的死亡率增加有关。目前的数据还表明,较高的循环 FGF23 水平与心血管死亡率、血管钙化和左心室肥厚有关;然而,关于透析患者中 FGF23 的作用的证据尚不完全,一些数据,尤其是关于心血管疾病(CVD)的数据,存在争议。本研究旨在评估伴有或不伴有 CVD 的血液透析患者中与 FGF23 相关的因素。在单一血液透析中心随机选择 76 名维持性血液透析患者。排除 8 名 FGF23 水平极高的患者后,纳入 68 名患者,其中 48 名男性和 46 名有 CVD 病史。患者的平均年龄为 64.4±12.1 岁,透析时间平均为 12.7±7.1 年。透析时间、平均尿素浓度(TAC-urea)、超滤率(UFR)、血液透析期间的血压、实验室数据和超声心动图参数,包括室间隔厚度(IVST)、左心室质量指数(LVMI)和射血分数均纳入单变量和多变量分析。在总队列和伴有或不伴有 CVD 的患者中,中位数 lgFGF23 水平分别为 2.14(四分位距,IQR-0.43 至-4.23)、2.01(-0.52 至 4.12)和 2.59(0.07 至 4.32),两组间无差异(p=0.14)。单变量分析显示,FGF23 与年龄(r=-0.12,p<0.01)、透析时间(r=-0.11,p<0.01)、TAC-urea(r=0.29,p=0.01)、UFR(r=0.26,p=0.04)、碱性磷酸酶(ALP;r=-0.27,p=0.03)、校正血清钙(cCa;r=0.32,p<0.01)、血清磷(iP,r=0.57,p<0.01)、全段甲状旁腺激素(iPTH;r=0.38,p<0.01)、IVST(r=0.30,p=0.01)和 LVMI(r=0.26,p=0.04)显著相关。多变量回归分析显示,FGF23 与 cCa(F=25.6,p<0.01)、iP(F=22.5,p<0.01)、iPTH(F=19.2,p<0.01)、ALP(F=5.34,p=0.03)和 UFR(F=3.94,p=0.05)显著相关。此外,根据 CVD 对患者进行分类后的单变量分析表明,FGF23 与 cCa(r=0.34,p=0.02)、iP(r=0.41,p<0.01)、iPTH(r=0.39,p=0.01)和 TAC-urea(r=0.45,p<0.01)显著相关,而在无 CVD 的患者中,仅 IVST(r=0.53,p=0.04)与 FGF23 相关。血液透析患者的 FGF23 水平极高,不仅与矿物质骨病相关因素有关,而且与 UFR 有关。此外,在伴有 CVD 的患者中,透析疗效可能与较低的 FGF23 水平有关。