Brighton and Sussex Medical School, Brighton, UK.
Nephrol Dial Transplant. 2012 Feb;27(2):727-33. doi: 10.1093/ndt/gfr316. Epub 2011 Jul 12.
Extra-skeletal calcification and disordered phosphate metabolism are hallmarks of chronic kidney disease-mineral bone disorder (CKD-MBD). Osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23) are increased in chronic kidney disease (CKD) and have been associated with arterial and cardiac dysfunction and reduced survival. Troponin T (cTnT) is released from cardiac myocytes under conditions of stress and is predictive of mortality across a range of renal functions. However, the utility of this biomarker was formerly limited by the lower limit of assay detection. The introduction of a high-sensitivity assay has enabled more detailed study of myocyte stress below the previous limit of detection. We studied the association of mediators of CKD-MBD with arterial stiffness and also of these mediators and arterial stiffness with myocardial damage in patients with CKD stages 3-4.
OPG and FGF-23 were measured in 200 CKD stages 3-4 patients. cTnT was measured using a high-sensitivity assay. Aortic stiffness was assessed using aortic pulse wave velocity (APWV).
Mean age was 69 ± 11 years, mean systolic and diastolic blood pressure was 151 ± 22/81 ± 11 mmHg and renal function was 33 ± 11 mL/min/1.73 m(2). OPG, FGF-23, high-sensitivity troponin T (hs-cTnT) and APWV all correlated with renal function. After multivariate analysis, OPG and age remained independently associated with aortic stiffness. OPG and FGF-23 were independently associated with hs-cTnT in addition to other non-traditional risk factors (Model R(2) = 0.596).
We have shown that changes in bone mediators and phosphate metabolism induced by CKD are independently associated with vascular and cardiomyocyte dysfunction. Our findings suggest that cardiac dysfunction may be specifically associated with such abnormalities in addition to recognized increases in vascular stiffness.
骨外钙化和磷酸盐代谢紊乱是慢性肾脏病-矿物质骨异常（CKD-MBD）的标志。骨保护素（OPG）和成纤维细胞生长因子 23（FGF-23）在慢性肾脏病（CKD）中增加，并与动脉和心脏功能障碍以及存活率降低有关。肌钙蛋白 T（cTnT）在心肌细胞受到应激时从心肌细胞中释放出来，可预测各种肾功能下的死亡率。然而，该生物标志物的实用性以前受到检测下限的限制。高敏检测方法的引入使我们能够在以前的检测限以下更详细地研究心肌细胞的应激情况。我们研究了 CKD-MBD 介质与动脉僵硬的关系，以及这些介质与 CKD 3-4 期患者心肌损伤的关系。
检测了 200 名 CKD 3-4 期患者的 OPG 和 FGF-23。使用高敏检测法测量 cTnT。采用主动脉脉搏波速度（APWV）评估主动脉僵硬程度。
平均年龄为 69 ± 11 岁，平均收缩压和舒张压为 151 ± 22/81 ± 11mmHg，肾功能为 33 ± 11mL/min/1.73m²。OPG、FGF-23、高敏肌钙蛋白 T（hs-cTnT）和 APWV 均与肾功能相关。多变量分析后，OPG 和年龄与主动脉僵硬仍独立相关。除其他非传统危险因素外，OPG 和 FGF-23 还与 hs-cTnT 独立相关（模型 R²=0.596）。
我们表明，CKD 引起的骨介质和磷酸盐代谢变化与血管和心肌细胞功能障碍独立相关。我们的发现表明，心脏功能障碍可能与血管僵硬的增加有关，也可能与这些异常有关。
