Komaba Hirotaka, Fuller Douglas S, Taniguchi Masatomo, Yamamoto Suguru, Nomura Takanobu, Zhao Junhui, Bieber Brian A, Robinson Bruce M, Pisoni Ronald L, Fukagawa Masafumi
Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan.
The Institute of Medical Sciences, Tokai University, Isehara, Japan.
Kidney Int Rep. 2020 Aug 20;5(11):1956-1964. doi: 10.1016/j.ekir.2020.08.013. eCollection 2020 Nov.
Elevated fibroblast growth factor 23 (FGF23) levels have been strongly associated with mortality in the predialysis and incident hemodialysis populations, but few studies have examined this relationship in a large cohort of prevalent hemodialysis patients and in particular among persons with high dialysis vintage. To address this, we analyzed data from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS).
We included 1122 prevalent hemodialysis patients from the J-DOPPS phase 5 (2012-2015) who had FGF23 measurements. We evaluated the association of FGF23 levels with all-cause mortality and cardiovascular composite outcome using Cox regression adjusted for potential confounders.
At study enrollment, median dialysis vintage was 5.8 years (interquartile range, 2.7-12.4 years) and median FGF23 level was 2113 pg/ml (interquartile range, 583-6880 pg/ml). During 3-year follow-up, 154 of the 1122 participants died. In adjusted analyses, higher FGF23 was associated with a greater hazard of death (hazard ratio per doubling of FGF23, 1.12; 95% confidence interval, 1.03-1.21); however, the association became weaker as the dialysis vintage increased and finally disappeared in the highest tertile (>9.4 years). Similar patterns of effect modification by dialysis vintage were observed for cardiovascular composite outcome and in time-dependent models.
Elevated FGF23 was associated with mortality and cardiovascular events in prevalent hemodialysis patients, but the association was attenuated at longer dialysis vintages. This novel finding suggests that long-term hemodialysis patients may be less susceptible to the detrimental effects of FGF23 or correlated biological processes, and additional studies are needed to gain understanding of these possibilities.
成纤维细胞生长因子23（FGF23）水平升高与透析前和新进入血液透析人群的死亡率密切相关，但很少有研究在大量的维持性血液透析患者队列中，特别是在透析龄较长的患者中研究这种关系。为了解决这个问题，我们分析了日本透析结果和实践模式研究（J-DOPPS）的数据。
我们纳入了J-DOPPS第5阶段（2012 - 2015年）的1122名接受维持性血液透析且进行了FGF23检测的患者。我们使用针对潜在混杂因素进行调整的Cox回归评估FGF23水平与全因死亡率和心血管复合结局之间的关联。
在研究入组时，中位透析龄为5.8年（四分位间距，2.7 - 12.4年），中位FGF23水平为2113 pg/ml（四分位间距，583 - 6880 pg/ml）。在3年的随访期间，1122名参与者中有154人死亡。在调整分析中，较高的FGF23与更高的死亡风险相关（FGF23每增加一倍，风险比为1.12；95%置信区间，1.03 - 1.21）；然而，随着透析龄的增加，这种关联变得更弱，最终在最高三分位数组（>9.4年）中消失。对于心血管复合结局和时间依赖性模型，观察到了类似的透析龄效应修正模式。
FGF23升高与维持性血液透析患者的死亡率和心血管事件相关，但在透析龄较长时这种关联减弱。这一新发现表明，长期血液透析患者可能对FGF23或相关生物学过程的有害影响不太敏感，需要进一步研究以了解这些可能性。
