Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease
Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease
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DOI：
10.1681/asn.2005010052
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发表时间：
2005-07-01
影响因子：
13.6
通讯作者：
Wolf, M
中科院分区：
文献类型：
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作者：
Gutierrez, O;Isakova, T;Wolf, M
高磷血症、骨化三醇缺乏和继发性甲状旁腺功能亢进症（SHPT）是慢性肾脏病（CKD）的常见并发症。成纤维细胞生长因子-23 (FGF-23) 是一种新型磷酸盐激素，也能抑制肾 α-羟化酶活性，因此可能参与 SHPT 的发病机制。测试了几个假设：FGF-23 随着肾功能下降而增加；与血清磷酸盐水平呈线性相关；与磷酸尿增加相关，与甲状旁腺激素 (PTH) 无关；并且与骨化三醇水平降低相关，与肾功能、高磷血症和维生素 D 储存无关。在 80 名 CKD 患者中测量了 FGF-23、PTH、25(OH)D-3、骨化三醇、钙、磷酸盐和尿磷酸盐排泄分数 (Fe,,,)。使用多元线性回归来检验假设。 FGF-23 和 PTH 与估计 GFR (eGFR) 呈负相关，而骨化三醇水平与 eGFR 呈线性相关。仅 12% 和 6% 的患者存在高磷血症和低钙血症，所有 eGFR 均 < 30。Fe 增加与 eGFR 降低相关，FGF-23 和 PTH 增加与 Fe-PO4 增加独立相关。 FGF-23 增加和 25(OH)D-3 减少是骨化三醇减少的独立预测因素，但通过调整 FGF-23，肾功能本身和高磷酸盐血症对骨化三醇水平的影响被完全消除。结论是，FGF-23 水平在 CKD 早期出现血清矿物质异常之前升高，并且与血清磷酸盐、Fe-PO4 和骨化三醇缺乏独立相关。 FGF-23 增加可能有助于在进展的 CKD 中维持正常的血清磷酸盐水平，但可能会加剧骨化三醇缺乏，因此可能是 SHPT 早期发病机制的核心因素。
Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal la-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D-3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe,,,) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was < 30. Increased Fe,,, was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe-PO4. Increased FGF-23 and decreased 25(OH)D-3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe-PO4, and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.