Background

Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the association of Syndecan-1 (SDC-1), Angiopoetin-2 (Ang-2), soluble thrombomodulin (sTM), vascular adhesion protein-1 (VAP-1) and interleukin-6 (IL-6) with fluid administration and balance among septic critical care patients and their association with development of acute kidney injury (AKI) and 90-day mortality.

Results

SDC-1, Ang-2, sTM, VAP-1 and IL-6 levels were measured at ICU admission from 619 patients with sepsis. VAP-1 decreased (p < 0.001) and IL-6 increased (p < 0.001) with increasing amounts of administered fluid, but other biomarkers did not show differences according to fluid administration. In linear regression models adjusted for IL-6, only VAP-1 was significantly associated with fluid administration on day 1 (p < 0.001) and the cumulative fluid balance on day 5/ICU discharge (p = 0.001). Of 415 patients admitted without AKI, altogether 112 patients (27.0%) developed AKI > 12 h from ICU admission (AKI_>12 h). They had higher sTM levels than patients without AKI, and after multivariable adjustment log, sTM level was associated with AKI_>12 h with OR (95% CI) of 12.71 (2.96–54.67), p = 0.001). Ninety-day non-survivors (n = 180; 29.1%) had higher SDC-1 and sTM levels compared to survivors. After adjustment for known confounders, log SDC-1 (OR [95% CI] 2.13 [1.31–3.49], p = 0.002), log sTM (OR [95% CI] 7.35 [2.29–23.57], p < 0.001), and log Ang-2 (OR [95% CI] 2.47 [1.44–4.14], p = 0.001) associated with an increased risk for 90-day mortality. Finally, patients who had high levels of all three markers, namely, SDC-1, Ang-2 and sTM, had an adjusted OR of 5.61 (95% CI 2.67–11.79; p < 0.001) for 90-day mortality.

Conclusions

VAP-1 and IL-6 associated with fluid administration on the first ICU day. After adjusting for confounders, sTM was associated with development of AKI after 12 h from ICU admission. SDC-1, Ang-2 and sTM were independently associated with an increased risk for 90-day mortality.

中文翻译：

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内皮和糖萼损伤生物标志物与输液，急性肾损伤的发生和90天死亡率的关联：来自FINNAKI观察性研究的数据。

背景

内皮和糖萼的损伤易导致血管渗漏，随后可能导致体液需求增加和预后不良。在这项对17个芬兰重症监护病房进行的多中心观察性芬兰急性肾损伤（FINNAKI）前瞻性队列研究中，我们研究了Syndecan-1（SDC-1），Angiopoetin-2（Ang-2），可溶性血栓调节蛋白（sTM），血管粘附蛋白1（VAP-1）和白细胞介素6（IL-6）在脓毒症重症监护患者中进行输液和平衡，并与急性肾损伤（AKI）和90-日死亡率。

结果

在ICU入院时对619名脓毒症患者的SDC-1，Ang-2，sTM，VAP-1和IL-6水平进行了测量。 随着液量的增加，VAP-1降低（p  <0.001），IL-6升高（p <0.001），但是根据液剂的使用，其他生物标志物未显示差异。在针对IL-6进行了调整的线性回归模型中，只有VAP-1与第1天输液显着相关（p  <0.001）和第5天/ ICU排出时的累积体液平衡（p  = 0.001）。在415例无AKI的患者中，共有112例（27.0％）从ICU入院_{> 12 h出现}AKI（AKI _{> 12 h}）。与没有AKI的患者相比，他们的sTM水平更高，经过多变量校正对数后，sTM水平与AKI _{> 12 h相关}，OR（95％CI）为12.71（2.96-54.67），p  = 0.001）。 与幸存者相比，有90天的非幸存者（n = 180； 29.1％）的SDC-1和sTM水平更高。调整已知混杂因素后，对数SDC-1（OR [95％CI] 2.13 [1.31-3.49]，p  = 0.002），对数sTM（OR [95％CI] 7.35 [2.29-23.57]，p  <0.001），和对数Ang-2（OR [95％CI] 2.47 [1.44-4.14]，p  = 0.001）与90天死亡率增加相关。最后，那些同时具有SDC-1，Ang-2和sTM这三种标记物的患者，其校正后的OR为5.61（95％CI 2.67-11.79； MS = 95）。p  <0.001）90天死亡率。

结论

VAP-1和IL-6在ICU第一天与输液有关。调整混杂因素后，sTM与ICU入院12小时后的AKI发生有关。SDC-1，Ang-2和sTM分别与90天死亡率增加的风险相关。