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Clin J Am Soc Nephrol. 2018 Apr 6;13(4):531-541. doi: 10.2215/CJN.10810917. Epub 2018 Mar 8.
Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured plasma FGF23 and other mineral metabolite levels in two cohorts of critically ill patients (=1527). We included 817 patients with AKI requiring RRT who enrolled in the ARF Trial Network (ATN) study, and 710 patients with and without AKI who enrolled in the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study. We hypothesized that higher FGF23 levels at enrollment are independently associated with higher 60-day mortality.
In the ATN study, patients in the highest compared with lowest quartiles of C-terminal (cFGF23) and intact FGF23 (iFGF23) had 3.84 (95% confidence interval, 2.31 to 6.41) and 2.08 (95% confidence interval, 1.03 to 4.21) fold higher odds of death, respectively, after adjustment for demographics, comorbidities, and severity of illness. In contrast, plasma/serum levels of parathyroid hormone, vitamin D metabolites, calcium, and phosphate were not associated with 60-day mortality. In the VALID study, patients in the highest compared with lowest quartiles of cFGF23 and iFGF23 had 3.52 (95% confidence interval, 1.96 to 6.33) and 1.93 (95% confidence interval, 1.12 to 3.33) fold higher adjusted odds of death.
Higher FGF23 levels are independently associated with greater mortality in critically ill patients.
矿物质代谢紊乱是危重病的一种常见且潜在的适应性特征，尤其是在急性肾损伤（AKI）患者中，但它与死亡的关系尚未得到全面研究。我们试图确定在需要肾脏替代治疗（RRT）的 AKI 危重病患者以及在伴有或不伴有 AKI 的一般危重病患者中，成骨细胞衍生的维生素 D 调节激素成纤维细胞生长因子 23（FGF23）的血浆水平升高是否与死亡有前瞻性关联。
设计、地点、参与者和测量方法：我们测量了两个危重病患者队列（=1527 例）的血浆 FGF23 和其他矿物质代谢物水平。我们纳入了 817 例需要 RRT 的 AKI 患者，他们参加了急性肾损伤试验网络（ATN）研究，以及 710 例伴有或不伴有 AKI 的患者，他们参加了急性肺损伤生物标志物验证用于诊断（VALID）研究。我们假设在入组时更高的 FGF23 水平与更高的 60 天死亡率独立相关。
在 ATN 研究中，与最低四分位数相比，最高四分位数的 C 端（cFGF23）和完整 FGF23（iFGF23）的患者死亡的优势比分别为 3.84（95%置信区间，2.31 至 6.41）和 2.08（95%置信区间，1.03 至 4.21）。调整了人口统计学、合并症和疾病严重程度后，差异仍然显著。相比之下，甲状旁腺激素、维生素 D 代谢物、钙和磷酸盐的血浆/血清水平与 60 天死亡率无关。在 VALID 研究中，与最低四分位数相比，最高四分位数的 cFGF23 和 iFGF23 的患者死亡的调整优势比分别为 3.52（95%置信区间，1.96 至 6.33）和 1.93（95%置信区间，1.12 至 3.33）。
更高的 FGF23 水平与危重病患者的死亡率增加独立相关。
