Division of Nephrology and Hypertension, Department of Medicine, University of Miami, Miller School of Medicine, 1120 NW 14th St, Miami, FL 33136, USA.
JAMA. 2011 Jun 15;305(23):2432-9. doi: 10.1001/jama.2011.826.
A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease.
To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.
DESIGN, SETTING, AND PARTICIPANTS: A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.
All-cause mortality and end-stage renal disease.
At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2).
Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
在终末期肾病患者中，高水平的磷酸盐调节激素成纤维细胞生长因子 23（FGF-23）与死亡率相关，但在慢性肾脏病早期阶段的更大患者人群中，其与不良结局的关系知之甚少。
评估 FGF-23 作为慢性肾脏病患者不良结局的危险因素。
设计、地点和参与者：一项对 2003 年 6 月至 2008 年 9 月期间参加慢性肾功能不全队列的 3879 名慢性肾脏病 2 至 4 期患者的前瞻性研究。
全因死亡率和终末期肾病。
在研究入组时，平均（SD）估算肾小球滤过率（GFR）为 42.8（13.5）mL/min/1.73 m2，中位数 FGF-23 水平为 145.5 RU/mL（四分位距 [IQR]，96-239 参考单位 [RU]/mL）。在中位数为 3.5 年（IQR，2.5-4.4 年）的随访期间，266 名患者死亡（20.3/1000 人年），410 名患者进入终末期肾病（33.0/1000 人年）。在调整后的分析中，较高水平的 FGF-23 与死亡风险增加独立相关（每自然对数转换 FGF-23 的标准差，危险比 [HR]，1.5；95%置信区间 [CI]，1.3-1.7）。死亡率按 FGF-23 的四分位值升高：第二四分位数的 HR 为 1.3（95%CI，0.8-2.2），第三四分位数为 2.0（95%CI，1.2-3.3），第四四分位数为 3.0（95%CI，1.8-5.1）。在估算肾小球滤过率为 30 至 44 mL/min/1.73 m2 之间的参与者中，升高的成纤维细胞生长因子 23 与终末期肾病风险显著增加相关（HR，每 SD 的 FGF-23 自然对数转换的 FGF-23；95%CI，1.04-1.6）和 45 mL/min/1.73 m2 或更高（HR，1.7；95%CI，1.1-2.4），但低于 30 mL/min/1.73 m2 时则不然。
在肾功能相对保留的患者中，升高的 FGF-23 是终末期肾病的独立危险因素，也是慢性肾脏病谱中死亡率的独立危险因素。
