Division of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana.
Kidney360. 2022 Jul 5;3(9):1529-1541. doi: 10.34067/KID.0002192022. eCollection 2022 Sep 29.
Fibroblast growth factor 23 (FGF23) is a bone-derived phosphatonin that is elevated in chronic kidney disease (CKD) and has been implicated in the development of cardiovascular disease. It is unknown whether elevated FGF23 in CKD is associated with impaired cardiovascular functional capacity, as assessed by maximum exercise oxygen consumption (VOMax). We sought to determine whether FGF23 is associated with cardiovascular functional capacity in patients with advanced CKD and after improvement of VOMax by kidney transplantation.
We performed secondary analysis of 235 patients from the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) cohort, which recruited patients with stage 5 CKD who underwent kidney transplantation or were waitlisted and hypertensive controls. All patients underwent cardiopulmonary exercise testing (CPET) and echocardiography and were followed longitudinally for 1 year after study enrollment.
Patients across FGF23 quartiles differed in BMI (=0.004) and mean arterial pressure (<0.001) but did not significantly differ in sex (=0.5) or age (=0.08) compared with patients with lower levels of FGF23. Patients with higher FGF23 levels had impaired VOMax (Q1: 24.2±4.8 ml/min per kilogram; Q4: 18.6±5.2 ml/min per kilogram; <0.001), greater left ventricular mass index (LVMI; <0.001), reduced HR at peak exercise (<0.001), and maximal workload (<0.001). Kidney transplantation conferred a significant decline in FGF23 at 2 months (<0.001) before improvement in VOMax at 1 year (=0.008). Multivariable regression modeling revealed that changes in FGF23 was significantly associated with VOMax in advanced CKD (<0.001) and after improvement after kidney transplantation (=0.006). FGF23 was associated with LVMI before kidney transplantation (=0.003), however this association was lost after adjustment for dialysis status (=0.4). FGF23 was not associated with LVMI after kidney transplantation in all models.
FGF23 levels are associated with alterations in cardiovascular functional capacity in advanced CKD and after kidney transplantation. FGF23 is only associated with structural cardiac adaptations in advanced CKD but this was modified by dialysis status, and was not associated after kidney transplantation.
成纤维细胞生长因子 23（FGF23）是一种源于骨骼的磷酸激素，在慢性肾脏病（CKD）中升高，并与心血管疾病的发展有关。目前尚不清楚 CKD 中升高的 FGF23 是否与最大运动耗氧量（VOMax）评估的心血管功能能力受损有关。我们试图确定 FGF23 是否与晚期 CKD 患者的心血管功能能力有关，以及肾移植后 VOMax 改善后是否存在相关性。
我们对心肺运动试验在肾衰竭和肾移植后的（CAPER）队列中的 235 名患者进行了二次分析，该队列招募了接受肾移植或等待肾移植的 5 期 CKD 患者以及高血压对照组。所有患者均接受心肺运动测试（CPET）和超声心动图检查，并在研究入组后 1 年内进行纵向随访。
FGF23 四分位组患者的 BMI（=0.004）和平均动脉压（<0.001）不同，但与 FGF23 水平较低的患者相比，性别（=0.5）和年龄（=0.08）无显著差异。FGF23 水平较高的患者 VOMax 受损（Q1：24.2±4.8 ml/min/kg；Q4：18.6±5.2 ml/min/kg；<0.001）、左心室质量指数（LVMI）较大（<0.001）、运动峰值时 HR 降低（<0.001）、最大工作量降低（<0.001）。肾移植后 2 个月 FGF23 显著下降（<0.001），1 年后 VOMax 改善（=0.008）。多变量回归模型显示，在晚期 CKD 中，FGF23 的变化与 VOMax 显著相关（<0.001），在肾移植后改善时也显著相关（=0.006）。在肾移植前，FGF23 与 LVMI 相关（=0.003），但在调整透析状态后，这种相关性丧失（=0.4）。在所有模型中，肾移植后 FGF23 与 LVMI 均无相关性。
FGF23 水平与晚期 CKD 及肾移植后心血管功能能力的改变有关。在晚期 CKD 中，FGF23 仅与结构性心脏适应有关，但这种适应受透析状态的影响，肾移植后则无相关性。
