背景:成纤维细胞生长因子23(FGF23)在慢性肾脏疾病(CKD)相关的矿物质和骨骼疾病中起重要作用。高FGF23水平与非血液透析CKD患者贫血风险增加相关。FGF23也负调节小鼠的红细胞生成。我们假设较高的FGF23水平与血液透析患者的促红细胞生成素低反应性增加有关。
方法:该研究包括来自日本透析结果和实践模式研究(J-DOPPS)5期(2012-2015)的1044名患者。结果是红细胞生成刺激剂低反应性(ESA-hypo),定义为FGF23测量后4个月内平均Hgb<10g/dL和标准化平均ESA剂量>6000u/周。使用多变量调整逻辑广义估计方程回归模型估计ESA-hypo和FGF23之间的关联。
结果:FGF23水平较高的患者年龄较小,血清白蛋白水平较高,肌酐,白蛋白校正钙,磷,PTH,25(OH)-维生素D,并有较高百分比的静脉(IV)铁,IV维生素D和西那卡塞的使用。144例患者(13.8%)存在ESA-hypo。与FGF23水平的第三个五分之一相比,ESA-hypo的比值比(95%CI)为2.14(0.99,4.62)和1.74(0.74,4.11),分别。
结论:在维持性血液透析患者中,最低和最高水平的FGF23与较高的ESA-hypo几率相关,尽管这些关联没有统计学意义.FGF23与贫血的关系,特别是在低FGF23水平下ESA-hypo的风险增加,这可能是节能的结果,必须在更大的临床研究中证实。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.