Stevens Kathryn K, McQuarrie Emily P, Sands William, Hillyard Dianne Z, Patel Rajan K, Mark Patrick B, Jardine Alan G
Renal Research Group, ICAMS, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Int J Nephrol. 2011;2011:297070. doi: 10.4061/2011/297070. Epub 2011 Aug 9.
Elevated FGF-23 is a predictor of mortality and is associated with LVH in CKD. It may be a biomarker or a direct toxin. We assessed the relationship between FGF-23 and LVH in CKD using CMRI. In vitro we studied the effect of phosphate, FGF-23, and Klotho on E-selectin and VCAM production in HUVECs. FGF-23 concentration correlates negatively with eGFR and positively with LVMI. FGF-23 was an independent predictor of LVH in CKD. E-selectin and VCAM production was elevated in HUVECs cultured in high phosphate with FGF-23 or Klotho. This effect was attenuated in cells exposed to both FGF-23 and Klotho. FGF-23 is an independent predictor of LVH as measured by CMRI. We show preliminary data which supports that FGF-23 is toxic resulting in activation of the vascular endothelium. We do not prove causality with elevated FGF-23 and LVH. Further research should ascertain if lowering levels of FGF-23 translates to improved clinical outcomes.
FGF-23升高是死亡率的预测指标,且与慢性肾脏病(CKD)患者的左心室肥厚(LVH)相关。它可能是一种生物标志物或直接毒素。我们使用心脏磁共振成像(CMRI)评估了CKD患者中FGF-23与LVH之间的关系。在体外实验中,我们研究了磷酸盐、FGF-23和α-klotho对人脐静脉内皮细胞(HUVECs)中E-选择素和血管细胞黏附分子(VCAM)产生的影响。FGF-23浓度与估算肾小球滤过率(eGFR)呈负相关,与左心室质量指数(LVMI)呈正相关。FGF-23是CKD患者LVH的独立预测指标。在添加FGF-23或α-klotho的高磷培养基中培养的HUVECs中,E-选择素和VCAM的产生增加。在同时暴露于FGF-23和α-klotho的细胞中,这种效应减弱。通过CMRI测量,FGF-23是LVH的独立预测指标。我们展示的初步数据支持FGF-23具有毒性,可导致血管内皮激活。我们并未证实FGF-23升高与LVH之间存在因果关系。进一步的研究应确定降低FGF-23水平是否能改善临床结局。