Division of Nephrology, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea,
Kidney Blood Press Res. 2019;44(5):1166-1178. doi: 10.1159/000502526. Epub 2019 Sep 25.
The aims of this study were to measure changes in fibroblast growth factor 23 (FGF-23), neutrophil (elastase, lactoferrin)/platelet activation marker (mean platelet volume-to-platelet count ratio [MPR]), and angiogenin according to the stage of chronic kidney disease (CKD), and to evaluate the association of FGF-23, elastase, lactoferrin, MPR, and angiogenin with arterial stiffness using brachial-ankle pulse wave velocity (ba-PWV) in CKD patients.
According to the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the patients were allocated to five groups: (1) normal controls (eGFR ≥90 mL/min/1.73 m2 without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60-89 mL/min/1.73 m2; n = 17); (3) CKD stage 3 (eGFR 30-59 mL/min/1.73 m2; n = 22); (4) CKD stage 4 (eGFR 15-30 mL/min/1.73 m2; n = 17); and (5) CKD stage 5-hemodialysis (HD) (n = 30). All the patients were free of clinically apparent cardiovascular disease. Serum FGF-23, elastase, lactoferrin, and angiogenin concentrations and the MPR were measured to study the association of the above parameters with the clinical (age, sex, presence of diabetes mellitus, and blood pressure), biochemical (calcium, phosphorus, uric acid, intact parathyroid hormone [PTH], low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein), and ba-PWV values of the CKD patients.
(1) The mean ba-PWV values were 1,497.2 ± 206.4 cm/s in the controls, 1,649.0 ± 247.9 cm/s in the CKD stage 2 group (p < 0.05 vs. controls), 1,655.8 ± 260.3 cm/s in the CKD stage 3 group (p < 0.05 vs. controls), 1,823.0 ± 402.4 cm/s in the CKD stage 4 group (p < 0.05 vs. controls and CKD stages 2 and 3), and 1,905.2 ± 374.1 cm/s in the CKD stage 5-HD group (p < 0.05 vs. controls and CKD stage 2). (2) The mean log10(FGF-23) concentration values were 0.77 ± 0.27, 0.97 ± 0.48, 1.10 ± 0.35 (p < 0.05 vs. controls and CKD stage 2), 1.35 ± 0.48 (p < 0.05 vs. controls and CKD stages 2 and 3), and 2.12 ± 0.82 (p < 0.05 vs. controls and CKD stages 2-4); the mean angiogenin levels were 230.6 ± 70.5 pg/mL, 283.0 ± 53.5 pg/mL (p < 0.05 vs. controls), 347.3 ± 76.9 pg/mL (p < 0.05 vs. controls and CKD stage 2), 445.9 ± 90.6 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3), and 370.9 ± 142.4 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3). (3) In the stage 3-4 CKD/HD patients, the mean elastase-to-neutrophil and lactoferrin-to-neutrophil ratios were significantly lower than in the controls and the stage 2 CKD patients. (4) Our multivariate linear regression analyses showed that age, pulse pressure, mean arterial pressure, PTH, and FGF-23 were independently associated with ba-PWV values.
Circulating FGF-23 and angiogenin concentrations gradually increased as CKD advanced, whereas neutrophil activation markers were significantly lower in the stage 3-4 CKD/HD patients than in the controls and stage 2 CKD patients. FGF-23 was weakly associated with ba-PWV values in patients with CKD/HD and no previous cardiovascular disease.
本研究旨在测量成纤维细胞生长因子 23（FGF-23）、中性粒细胞（弹性蛋白酶、乳铁蛋白）/血小板活化标志物（血小板平均体积与血小板计数的比值[MPR]）和血管生成素在慢性肾脏病（CKD）各阶段的变化，并评估 FGF-23、弹性蛋白酶、乳铁蛋白、MPR 和血管生成素与 CKD 患者肱踝脉搏波速度（ba-PWV）的动脉僵硬度的相关性。
根据慢性肾脏病流行病学合作（CKD-EPI）方程计算的估计肾小球滤过率（eGFR），将患者分为五组：（1）正常对照组（eGFR≥90 mL/min/1.73 m2，无病理、尿液[蛋白尿]、血液[电解质]和影像学异常；n=22）；（2）CKD 期 2 组（eGFR 60-89 mL/min/1.73 m2；n=17）；（3）CKD 期 3 组（eGFR 30-59 mL/min/1.73 m2；n=22）；（4）CKD 期 4 组（eGFR 15-30 mL/min/1.73 m2；n=17）；（5）CKD 期 5 组-血液透析（HD）组（n=30）。所有患者均无明显的心血管疾病。测量血清 FGF-23、弹性蛋白酶、乳铁蛋白和血管生成素浓度，并研究上述参数与 CKD 患者的临床（年龄、性别、糖尿病和血压）、生化（钙、磷、尿酸、全段甲状旁腺激素[PTH]、低密度脂蛋白胆固醇和高敏 C 反应蛋白）和 ba-PWV 值的相关性。
（1）对照组的平均 ba-PWV 值为 1497.2±206.4 cm/s，CKD 期 2 组为 1649.0±247.9 cm/s（p<0.05 与对照组），CKD 期 3 组为 1655.8±260.3 cm/s（p<0.05 与对照组），CKD 期 4 组为 1823.0±402.4 cm/s（p<0.05 与对照组和 CKD 期 2 和 3 组），CKD 期 5-HD 组为 1905.2±374.1 cm/s（p<0.05 与对照组和 CKD 期 2）。（2）log10（FGF-23）浓度的平均数值分别为 0.77±0.27、0.97±0.48、1.10±0.35（p<0.05 与对照组和 CKD 期 2）、1.35±0.48（p<0.05 与对照组和 CKD 期 2 和 3）和 2.12±0.82（p<0.05 与对照组和 CKD 期 2-4）；血管生成素的平均水平分别为 230.6±70.5 pg/mL、283.0±53.5 pg/mL（p<0.05 与对照组）、347.3±76.9 pg/mL（p<0.05 与对照组和 CKD 期 2）、445.9±90.6 pg/mL（p<0.05 与对照组和 CKD 期 2 和 3）和 370.9±142.4 pg/mL（p<0.05 与对照组和 CKD 期 2 和 3）。（3）在 CKD 期 3-4/HD 患者中，弹性蛋白酶/中性粒细胞和乳铁蛋白/中性粒细胞的比值明显低于对照组和 CKD 期 2 患者。（4）我们的多元线性回归分析表明，年龄、脉压、平均动脉压、PTH 和 FGF-23 与 ba-PWV 值独立相关。
随着 CKD 的进展，循环中 FGF-23 和血管生成素的浓度逐渐升高，而 CKD 期 3-4/HD 患者的中性粒细胞活化标志物明显低于对照组和 CKD 期 2 患者。在无先前心血管疾病的 CKD/HD 患者中，FGF-23 与 ba-PWV 值的相关性较弱。
