Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D.
Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D.
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成纤维细胞生长因子23（FGF 23）是一种激素，已知可控制体内维生素D，磷酸盐和钙的水平。有证据表明，慢性肾脏疾病患者的高水平FGF 23可能会增加死亡风险。这项研究的目的是看看那些身体极度不适（被送进重症监护室）的患者，如果FGF 23水平高，是否比FGF 23水平低的患者更容易死亡。我们调查了两项重症监护研究的患者。我们发现，与FGF 23水平较低的患者相比，入院时FGF 23水平较高的患者死亡风险较高。这适用于没有慢性肾脏疾病的患者以及维生素D水平正常或低的患者。这可能意味着FGF 23可以以一种以前未探索的方式影响我们免疫系统的工作方式。随着更多的研究，治疗FGF 23水平可能是提高重症监护患者生存率的一种方法。背景：成纤维细胞生长因子（FGF 23）是一种内分泌激素，与维生素D、磷酸盐和钙的稳态有关。升高的血清FGF 23是已知的慢性肾病（CKD）患者死亡率的独立危险因素。我们的目的是确定FGF 23水平与危重患者死亡率之间是否存在类似的关系。研究方法：在接受维生素D补充的两个单独的患者组中通过ELISA测量血浆FGF 23水平：危重病患者（VITdAL-ICU试验，n = 475）和择期食管切除术患者（VINDALOO试验，n = 76）。分别在30天和180天或2年时记录死亡率数据。还测量了健康对照组中的FGF 23水平（n = 27）。结果如下：FGF 23升高（四分位数4与四分位数1-3）与危重病患者短期（30和180天）死亡率增加（p < 0.001）和食管切除术患者长期（2年）死亡率增加（p = 0.0149）相关。死亡患者的FGF 23水平显著高于存活患者：在危重病队列中，死亡患者的FGF 23水平为1194.6 pg/mL（范围为0- 14，000），而存活患者的FGF 23水平为120.4 pg/mL（范围= 15- 14，000）（p = 0.0462）。在食管切除术队列中，死亡者的水平为1304 pg/mL（范围= 154- 77，800），而存活者的水平为644 pg/mL（范围= 179- 54，894）（p < 0.001）。发现这与维生素D或CKD状态无关（危重病p = 0.3507;食管切除术p = 0.3800）。健康对照中的FGF 23水平与食管切除术患者中观察到的水平相似（p = 0.4802）。结论：在食管切除术后队列和需要重症监护的危重病患者队列中，基线血清FGF 23升高与死亡率增加相关。这与维生素D状态、补充剂或CKD状态无关，这表明在危重病的急性和恢复期存在不依赖维生素D的FGF 23作用机制，需要进一步研究。
Fibroblast Growth Factor 23 (FGF23) is a hormone which is known to control the levels of vitamin D, phosphate, and calcium in the body. There is evidence that high levels of FGF23 in patients with chronic kidney disease may increase the risk of death. The aim of this study is to see if patients who are extremely unwell (admitted to intensive care) with high levels of FGF23 are more likely to die than patients with lower levels. We investigated patients from two intensive care studies. We showed that patients who had higher FGF23 levels when they were admitted had a higher risk of death compared to patients with lower FGF23 levels. This applied to patients without chronic kidney disease as well as those with normal or low vitamin D levels. This may mean that FGF23 can affect the way our immune system works in a previously unexplored way. With more research, treating FGF23 levels might be a way to improve the survival of intensive care patients. Background: Fibroblast Growth Factor (FGF23) is an endocrine hormone classically associated with the homeostasis of vitamin D, phosphate, and calcium. Elevated serum FGF23 is a known independent risk factor for mortality in chronic kidney disease (CKD) patients. We aimed to determine if there was a similar relationship between FGF23 levels and mortality in critically ill patients. Methods: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 76). Mortality data were recorded at 30 and 180 days or at two years, respectively. FGF23 levels in a healthy control cohort were also measured (n = 27). Results: Elevated FGF23 (quartile 4 vs. quartiles 1–3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients (p < 0.001) and long-term (two-year) mortality in oesophagectomy patients (p = 0.0149). Patients who died had significantly higher FGF23 levels than those who survived: In the critical illness cohort, those who died had 1194.6 pg/mL (range 0–14,000), while those who survived had 120.4 pg/mL (range = 15–14,000) (p = 0.0462). In the oesophagectomy cohort, those who died had 1304 pg/mL (range = 154–77,800), while those who survived had 644 pg/mL (range = 179–54,894) (p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients (p = 0.4802). Conclusions: Elevated baseline serum FGF23 is correlated with increased mortality in both the post-oesophagectomy cohort and the cohort of patients with critical illness requiring intensive care admission. This was independent of vitamin D status, supplementation, or CKD status, which suggests the presence of vitamin D-independent mechanisms of FGF23 action during the acute and convalescent stages of critical illness, warranting further investigation.
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影响因子：
13.6
作者：
Leaf, David E.;Jacob, Kirolos A.;Waikar, Sushrut S.
通讯作者：
Waikar, Sushrut S.
影响因子：
3
作者：
Matthews, L. Ray;Ahmed, Yusuf;Wilson, Kenneth L.;Griggs, Diane D.;Danner, Omar K.
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Danner, Omar K.
影响因子：
3.2
作者：
Feng JQ;Ye L;Schiavi S
通讯作者：
Schiavi S
影响因子：
1.1
作者：
Lima F;El-Husseini A;Monier-Faugere MC;David V;Mawad H;Quarles D;Malluche HH
通讯作者：
Malluche HH
影响因子：
19.6
作者：
Leaf DE;Christov M;Jüppner H;Siew E;Ikizler TA;Bian A;Chen G;Sabbisetti VS;Bonventre JV;Cai X;Wolf M;Waikar SS
通讯作者：
Waikar SS