Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Nephrol Dial Transplant. 2019 Dec 1;34(12):2051-2057. doi: 10.1093/ndt/gfy315.
Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin-angiotensin-aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients.
This was a cross-sectional study encompassing 180 CKD patients Stage 1-5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis.
The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman's rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship.
FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.
最近的研究表明，磷酸酯酶激素成纤维细胞生长因子 23（FGF23）参与了肾钠排泄和血压的调节。有证据表明，它可以通过调节远端肾小管中的钠-氯共转运体（NCC）发挥直接作用，也可以通过与肾素-血管紧张素-醛固酮系统相互作用发挥间接作用。然而，目前缺乏关于 FGF23 与肾钠调节之间关联的临床数据。在此，我们研究了非透析慢性肾脏病（CKD）患者中 FGF23 与肾钠处理和血压之间的关联。
这是一项横断面研究，纳入了 180 名接受肾活检的 CKD 患者（1 期-5 期）。在基线时测量了血浆完整 FGF23、24 小时尿钠排泄量、钠排泄分数（FENa）和血压。通过多元回归分析探讨了 FGF23 与肾钠处理之间的关系。
研究对象的中位年龄为 52.8 岁，60.6%为男性，中位估算肾小球滤过率（eGFR）为 50.6ml/min/1.73m2。在单变量分析中，FGF23 与 FENa 呈正相关（Spearman 相关系数为 0.47；P<0.001），与收缩压呈正相关（相关系数为 0.17，P<0.05），但与血浆钠、24 小时尿钠排泄量或平均动脉血压无关。在调整潜在混杂因素后，FGF23 与 FENa 的相关性仍然显著（多变量校正β系数为 0.60，P<0.001）。在 eGFR<60ml/min/1.73m2 的 107 名患者和使用利尿剂的 73 名患者中，这种相关性更强（β=0.47，P=0.04 和β=0.88，P<0.001）。用实测肾小球滤过率替代估算肾小球滤过率进行调整并未改变这种关系。
FGF23 与非透析 CKD 患者的 FENa 增加独立相关。这些数据不支持 FGF23 导致临床显著钠潴留的观点。需要进一步的研究来探索这种关联的潜在机制。
