Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.
Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.
复制标题
DOI：
10.1056/nejmoa0706130
复制
发表时间：
2008-08-07
期刊：
影响因子：
--
通讯作者：
Wolf M
中科院分区：
文献类型：
--
作者：
Gutiérrez OM;Mannstadt M;Isakova T;Rauh-Hain JA;Tamez H;Shah A;Smith K;Lee H;Thadhani R;Jüppner H;Wolf M
成纤维细胞生长因子23（FGF-23）是一种激素，可增加磷酸盐的尿排泄率并抑制肾脏产生1，25-二羟维生素D，从而有助于缓解肾病患者的高磷酸盐血症。高磷酸盐血症和低1，25-二羟维生素D水平与慢性肾病患者的死亡率相关，但FGF-23水平对死亡率的影响尚不清楚。我们根据10，044例开始血液透析治疗的患者的血清磷酸盐水平检查了死亡率，然后分析了在血液透析治疗第一年期间死亡的200例受试者和存活的200例受试者的嵌套病例对照样本中的FGF-23水平和死亡率。我们假设血液透析开始时FGF-23水平升高与死亡率增加相关。与正常水平（3.5 ~ 4.5 mg/dl [1.1 ~ 1.4 mmol/L]）相比，血清磷水平最高四分位数（>5.5 mg/dl [1.8 mmol/L]）与多变量校正死亡风险增加20%相关（危险比，1.2; 95%置信区间[CI]，1.1 ~ 1.4）。病例组的C-末端FGF-23（cFGF-23）水平中位数显著高于对照组（2260 vs. 1406参考单位/毫升，P<0.001）。多变量校正分析显示，当在连续量表上检查时，FGF-23水平的增加与死亡风险的单调增加相关，（对数转换的cFGF-23值每单位增加的比值比为1.8; 95% CI，1.4 - 2.4）或四分位数，四分位数1作为参考类别（第2个四分位数的比值比为1.6 [95% CI，0.8 - 3.3];第3个四分位数的比值比为4.5 [95% CI，2.2 - 9.4];第4个四分位数的比值比为5.7 [95% CI，2.6 - 12.6]）。在开始血液透析治疗的患者中，FGF-23水平升高似乎与死亡率独立相关。未来的研究可能会调查FGF-23是否是一种潜在的生物标志物，可用于指导慢性肾病患者磷平衡的管理策略。
Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown. We examined mortality according to serum phosphate levels in a prospective cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case–control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment. We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality. Serum phosphate levels in the highest quartile (>5.5 mg per deciliter [1.8 mmol per liter]) were associated with a 20% increase in the multivariable adjusted risk of death, as compared with normal levels (3.5 to 4.5 mg per deciliter [1.1 to 1.4 mmol per liter]) (hazard ratio, 1.2; 95% confidence interval [CI], 1.1 to 1.4). Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in case subjects than in controls (2260 vs. 1406 reference units per milliliter, P<0.001). Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale (odds ratio per unit increase in log-transformed cFGF-23 values, 1.8; 95% CI, 1.4 to 2.4) or in quartiles, with quartile 1 as the reference category (odds ratio for quartile 2, 1.6 [95% CI, 0.8 to 3.3]; for quartile 3, 4.5 [95% CI, 2.2 to 9.4]; and for quartile 4, 5.7 [95% CI, 2.6 to 12.6]). Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment. Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease.