Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan.
Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.
Nephrology (Carlton). 2021 Jan;26(1):46-53. doi: 10.1111/nep.13765. Epub 2020 Aug 20.
Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)-related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non-haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients.
The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phase 5 (2012-2015). The outcome was erythropoiesis-stimulating agent hyporesponsiveness (ESA-hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA-hypo and FGF23 was estimated using multivariable-adjusted logistic generalized estimating equation regression models.
Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, 25(OH)-vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA-hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA-hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively.
The lowest and highest levels of FGF23 were associated with higher odds of ESA-hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA-hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies.
成纤维细胞生长因子 23（FGF23）在慢性肾脏病（CKD）相关的矿物质和骨代谢紊乱中起着重要作用。非血液透析 CKD 患者中，FGF23 水平升高与贫血风险增加相关。FGF23 还在小鼠中负向调节红细胞生成。我们假设，血液透析患者中 FGF23 水平升高与促红细胞生成素反应性降低有关。
本研究纳入了日本透析结局和实践模式研究（J-DOPPS）第 5 期（2012-2015 年）的 1044 例患者。研究结局为促红细胞生成素反应性降低（ESA-hypo），定义为 FGF23 检测后 4 个月内平均 Hgb<10g/dL 且标准化平均 ESA 剂量>6000u/周。采用多变量调整后的逻辑广义估计方程回归模型评估 ESA-hypo 与 FGF23 之间的关系。
FGF23 水平较高的患者年龄较小，血清白蛋白、肌酐、校正钙、磷、PTH、25（OH）-维生素 D 水平较高，静脉（IV）铁、IV 维生素 D 和西那卡塞使用率较高。144 例患者（13.8%）存在 ESA-hypo。与 FGF23 水平的第三五分位相比，FGF23 水平最低和最高五分位的 ESA-hypo 比值比（95%CI）分别为 2.14（0.99，4.62）和 1.74（0.74，4.11）。
在维持性血液透析患者中，FGF23 水平最低和最高五分位与 ESA-hypo 的发生几率较高相关，但相关性无统计学意义。FGF23 与贫血的关系，尤其是 FGF23 水平较低时 ESA-hypo 风险增加，可能是节能的结果，这一结果必须在更大的临床研究中得到证实。
