成纤维细胞生长因子 23-klotho 轴与儿科慢性肾脏病患儿的组织多普勒超声心动图：一项前瞻性队列研究。
The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort study.
机构信息
Division of Pediatrics, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Astrid Lindgren Children's Hospital, Huddinge BUMM, Paradistorget 4, 5tr, S-141 47, Huddinge, Sweden.
出版信息
Pediatr Nephrol. 2018 Jan;33(1):147-157. doi: 10.1007/s00467-017-3766-5. Epub 2017 Aug 9.
BACKGROUND
Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD.
METHODS
This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI).
RESULTS
The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients (β = -0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (β = 1.8, p = 0.06). In addition, high log FGF23 (β = -0.43, p = 0.01) and low log Klotho (β = 0.44, p = 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e'/a') in CKD-T patients.
CONCLUSIONS
In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation.
背景
慢性肾脏病相关的矿物质和骨代谢紊乱（CKD-MBD）在儿科肾脏病患者中很常见，也是未来心血管疾病（CVD）的一个危险因素。成纤维细胞生长因子 23（FGF23）和 Klotho 是 CKD-MBD 的新的关键因子，并且被认为与 CVD 的发展有关。
方法
本前瞻性队列研究纳入了 74 名儿科患者，其中 31 名患有 CKD（年龄范围 0.8-18.8 岁，肾小球滤过率（GFR）范围 9-68 mL/min/1.73 m），43 名移植患者（CKD-T；年龄范围 3.3-17.7 岁，GFR 范围 10-99 mL/min/1.73 m），每年进行 3 年的检查。我们使用超声心动图脉冲波多普勒（PWD）和彩色组织多普勒成像（cc-TDI）评估 FGF23 和可溶性 Klotho 的纵向变化模式和预测因素，以及与心脏重构和功能的相关性。
结果
尽管存在低磷血症和正常的 Klotho 水平，CKD 患者的高 FGF23 水平（≥95 百分位）的患病率为 60%，而 CKD-T 患者的患病率为 42%。基线时的低 GFR 是 CKD 和 CKD-T 患者随访期间高平均 log FGF23 的预测因素（β=-0.2，p<0.001）。在 CKD 患者中，高 log FGF23 z 分数与左心室质量指数（LVMI）升高呈临界显著相关（β=1.8，p=0.06）。此外，高 log FGF23（β=-0.43，p=0.01）和低 log Klotho（β=0.44，p=0.006）与 CKD-T 患者左心室舒张功能恶化（cc-TDI e'/a'）相关。
结论
在儿科 CKD 和 CKD-T 患者中，尽管磷酸盐水平得到了很好的控制，但随着肾功能衰竭的进展，FGF23 水平升高，Klotho 水平下降。调整后，高 FGF23 和低 Klotho 水平与左心室舒张功能的纵向恶化密切相关。FGF23 和 Klotho 在儿科 CKD 患者心脏发病率中的潜在作用需要进一步研究。
Zotero 插件