Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients
Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients
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DOI：
10.1186/s13054-020-02888-5
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发表时间：
2020-04-22
期刊：
影响因子：
15.1
通讯作者：
Legrand, Matthieu
中科院分区：
文献类型：
--
作者：
Depret, Francois;Amzallag, Juliette;Legrand, Matthieu
背景二肽基肽酶3（Dipeptidyl peptidase-3，DPP 3）是一种金属肽酶，其裂解生物活性肽，特别是血管紧张素II，并参与炎症调节。DPP 3被认为是一种心肌收缩因子，并参与急性疾病的循环衰竭，可能是由于血管紧张素II裂解。在这项研究中，我们评估了严重烧伤患者血浆DPP 3水平与预后（死亡率和血流动力学衰竭）之间的关系。方法在这项前瞻性队列研究的生物标志物分析中，我们纳入了两个三级烧伤重症监护病房的重症成人烧伤患者。在入院时（DPP 3（给药））和3天后测量DPP 3。主要终点为90天死亡率。次要终点为血流动力学衰竭和急性肾损伤（阿基）。结果111例患者连续入组。中位年龄为48（32.5-63）岁，烧伤总表面积的中位值为35%（25-53.5），烧伤严重程度指数（ABSI）为8（7-11）。90天死亡率为32%。非存活者的中位DPP 3（给药）显著高于存活者（53.3 ng/mL [IQR 28.8-103.5] vs 27.1 ng/mL [IQR 19.4-38.9]; p < 0.0001）。与高DPP 3（给药）但在第3天水平降低的患者相比，DPP 3持续升高的患者死亡风险增加。循环衰竭患者的DPP 3（给药）（39.2 ng/mL [IQR 25.9-76.1] vs 28.4 ng/mL [IQR 19.8-39.6]; p = 0.001）以及阿基患者（49.7 ng/mL [IQR 30.3-87.3] vs 27.6 ng/mL [IQR 19.4-41.4]; p = 0.001）更高。DPP 3（给药）在ABSI（添加chi（2）12.2，p = 0.0005）、入院时序贯器官衰竭评估（SOFA）评分（添加chi（2）4.9，p = 0.0268）和入院时血浆乳酸（添加chi（2）6.9，p = 0.0086）的基础上增加了预测值，以预测前48小时内的循环衰竭。结论严重烧伤患者入院时血浆DPP 3浓度与死亡、循环衰竭和阿基风险增加相关。应探讨DPP 3血浆水平是否可以识别对替代血流动力学支持策略（如静脉内血管紧张素II）有反应的患者。
Background Dipeptidyl peptidase-3 (DPP3) is a metallopeptidase which cleaves bioactive peptides, notably angiotensin II, and is involved in inflammation regulation. DPP3 has been proposed to be a myocardial depressant factor and to be involved in circulatory failure in acute illnesses, possibly due to angiotensin II cleavage. In this study, we evaluated the association between plasmatic DPP3 level and outcome (mortality and hemodynamic failure) in severely ill burn patients. Methods In this biomarker analysis of a prospective cohort study, we included severely ill adult burn patients in two tertiary burn intensive care units. DPP3 was measured at admission (DPP3(admin)) and 3 days after. The primary endpoint was 90-day mortality. Secondary endpoints were hemodynamic failure and acute kidney injury (AKI). Results One hundred and eleven consecutive patients were enrolled. The median age was 48 (32.5-63) years, with a median total body surface area burned of 35% (25-53.5) and Abbreviated Burn Severity Index (ABSI) of 8 (7-11). Ninety-day mortality was 32%. The median DPP3(admin) was significantly higher in non-survivors versus survivors (53.3 ng/mL [IQR 28.8-103.5] versus 27.1 ng/mL [IQR 19.4-38.9]; p < 0.0001). Patients with a sustained elevated DPP3 had an increased risk of death compared to patients with high DPP3(admin) but decreased levels on day 3. Patients with circulatory failure had higher DPP3(admin) (39.2 ng/mL [IQR 25.9-76.1] versus 28.4 ng/mL [IQR 19.8-39.6]; p = 0.001) as well as patients with AKI (49.7 ng/mL [IQR 30.3-87.3] versus 27.6 ng/mL [IQR 19.4-41.4]; p = 0.001). DPP3(admin) added prognostic value on top of ABSI (added chi(2) 12.2, p = 0.0005), Sequential Organ Failure Assessment (SOFA) score at admission (added chi(2) 4.9, p = 0.0268), and plasma lactate at admission (added chi(2) 6.9, p = 0.0086) to predict circulatory failure within the first 48 h. Conclusions Plasma DPP3 concentration at admission was associated with an increased risk of death, circulatory failure, and AKI in severely burned patients. Whether DPP3 plasma levels could identify patients who would respond to alternative hemodynamic support strategies, such as intravenous angiotensin II, should be explored.