摘要：据6月15日《美国医学会杂志》上的一则研究披露，那些内分泌激素成纤维细胞生长因子23 （它参与磷代谢调节）水平增加的处于早期慢性肾病的患者与其发生终末期肾病及死亡风险的增加有关。
成纤维细胞生长因子23 (FGF-23)在循环中的水平会随着肾功能的衰退而进行性地增加。根据文章的背景资料，FGF-23的高浓度与终末期肾病患者的死亡有关，但人们对 FGF-23与处于慢性肾病早期的较大病人群体的不良后果之间的关系所知甚少。
迈阿密大学米勒医学院的Tamara Isakova, M.D., M.M.Sc.及其同事对3879名处于第二期至第四期慢性肾病患者的FGF-23浓度的增加与死亡和终末期肾病风险之间的关系进行了调查。这些试验参与者在2003年6月至2008年9月间被纳入慢性肾功能不全的群组研究之中。
在刚加入该项研究的时候，这些患者的平均肾小球滤过率（GFR;这是对肾脏滤过并清除废物能力的测定）估算值为42.8 mL/min/1.73 m2。在中位数（中点）为3.5年的随访中，有266位参与者死亡，有410人进展到了终末期肾病。研究人员发现，那些死亡或进展到终末期肾病患者的FGF-23中位数水平显著高于那些无事件发生患者的FGF-23中位数水平。研究人员写道：“在经过人口学特征校正之后，GFR估算值和其它慢性肾病特异性风险因子不会改变在未经校正的分析中所观察到的FGF-23的浓度增加与死亡风险之间的关系。处于最高四分位的患者的死亡风险比最低四分位患者的死亡风险要高4.3倍，而中间两个四分位的患者的死亡风险则处于中间水平。”在经过充分校正的模型中，在整个FGF-23浓度范围内，死亡风险的梯度增加都持续存在。
在经过充分校正的分析中，GFR估算值的下降是终末期肾病的最强的预测因子，而GFR估算值可修正FGF-23与终末期肾病风险之间的关系。
“如果本研究的结果得到证实，而且实验性的研究支持FGF-23有直接毒性的假说的话，未来的研究应该评估降低FGF-23的治疗或预防性策略是否会改善病人的结果。”
FGF-23蛋白三维结构
生物探索推荐英文原文报道：
Patients with early-stage chronic kidney disease and elevated levels of certain hormone more likely to experience poorer outcomes
CHICAGO – Patients in the early stages of chronic kidney disease who had elevated levels of the endocrine hormone fibroblast growth factor 23 (that regulates phosphorus metabolism) had an associated increased risk of end-stage renal disease and death, according to a study in the June 15 issue of JAMA.
Circulating levels of fibroblast growth factor 23 (FGF-23) increase progressively as kidney function declines. A high level of 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 larger population of patients with earlier stages of chronic kidney disease, according to background information in the article.
Tamara Isakova, M.D., M.M.Sc., of the University of Miami Miller School of Medicine, and colleagues examined the relationship between elevated FGF-23 levels and risk of death and end-stage renal disease in 3,879 individuals with chronic kidney disease stages 2 through 4. The participants were enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.
At study enrollment, the average estimated glomerular filtration rate (GFR; measure of the kidneys' ability to filter and remove waste products) was 42.8 mL/min/1.73 m2. During a median (midpoint) follow-up of 3.5 years, 266 participants died and 410 reached end-stage renal disease. The researchers found that median FGF-23 levels were significantly higher in those who died or reached end-stage renal disease than in those who remained event-free. “Adjusting for demographic characteristics, estimated GFR and other chronic kidney disease-specific risk factors did not alter the relationship between elevated FGF-23 levels and risk of death observed in unadjusted analyses. Participants in the highest vs. the lowest quartile demonstrated a 4.3-fold greater risk of death, and the intermediate quartiles demonstrated intermediate risks,” the researchers write. In the fully adjusted models, the graded increase in risk of death persisted across the spectrum of FGF-23 levels.
Reduced estimated GFR was the strongest predictor of end-stage renal disease in fully adjusted analysis, and estimated GFR modified the relationship between FGF-23 and risk of end-stage renal disease.
“If the results of the current study are confirmed and experimental studies support the hypothesis of direct toxicity of FGF-23, future research should evaluate whether therapeutic or preventative strategies that lower FGF-23 can improve outcomes.”
生物探索推荐英文论文摘要：
Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney Disease
Context 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.
Objective 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 participantswith chronic kidney disease stages 2 through 4 who enrolled in the ChronicRenal Insufficiency Cohort between June 2003 and September 2008.
Main Outcome Measures All-cause mortality and end-stage renal disease.
Results At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m2, 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 m2 (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 m2 or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m2.
Conclusion Elevated FGF-23 is an independent risk factor for end-stage renaldisease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
KEYWORDS: fibroblast growth facto, r 23, kidney, disease, s, kidney, failure,chronic, , mortality, outcome assessment (health care), risk facto.rs.
