PDF(Pubmed)
Abstract：
UNASSIGNED: Previous work has identified two AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes using biospecimens collected in the emergency department and test for differential response to restrictive versus liberal fluid strategy in sepsis-induced hypotension in the CLOVERS trial.
UNASSIGNED: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction.
UNASSIGNED: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen\'s Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03).
UNASSIGNED: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.
UNASSIGNED: We applied a previously validated 3-biomarker model using plasma angiopietin-1 and 2, and soluble tumor necrosis factor receptor-1 to classify sub-phenotypes in patients with kidney dysfunction (AKI or end-stage kidney disease [ESKD]). We also compared a de novo latent class analysis (LCA) to the 3-biomarker based sub-phenotypes. Kaplan-Meier estimates were used to test for differences in outcomes and sub-phenotype by treatment interaction.
UNASSIGNED: Among 1289 patients, 846 had kidney dysfunction on enrollment and the 3-variable prediction model identified 605 as SP1 and 241 as SP2. The optimal LCA model identified two sub-phenotypes with high correlation with the 3-biomarker model (Cohen\'s Kappa 0.8). The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and SOFA scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had a reduction in 28-day mortality with a restrictive fluid strategy versus a liberal fluid strategy (26% vs 41%), while patients with SP1 had no difference in 28-day mortality (10% vs 11%) (p-value-for-interaction = 0.03).
UNASSIGNED: Sub-phenotypes can be identified in the emergency department that respond differently to fluid strategy in sepsis. Identification of these sub-phenotypes could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.
摘要：
以前的工作已经确定了两种AKI亚表型（SP1和SP2），其特征在于炎症和内皮功能障碍的差异。在这里，我们使用在急诊科收集的生物标本鉴定了这些亚表型，并在CLOVERS试验中测试了对脓毒症诱导的低血压的限制性和宽松性液体策略的差异反应。方法我们应用先前验证的3-生物标志物模型，使用血浆血管色素-1和2以及可溶性肿瘤坏死因子受体-1对肾功能不全（AKI或终末期肾病[ESKD]）患者的亚表型进行分类。我们还将从头潜在类别分析(LCA)与基于3-生物标志物的亚表型进行了比较。Kaplan-Meier估计用于通过治疗相互作用检验结果和亚表型的差异。结果1289例患者中,846在登记时具有肾功能障碍,并且3变量预测模型将605鉴定为SP1,并且将241鉴定为SP2。最佳LCA模型确定了与3-生物标志物模型(Cohen'sKappa0.8)高度相关的两个亚表型。与AKI分期和SOFA评分无关，SP2中28天和90天死亡率的风险高于SP1。SP2患者，以更严重的内皮损伤和炎症为特征，限制性液体策略与自由液体策略相比，28天死亡率降低（26％vs41％），而SP1患者的28天死亡率无差异(10%vs11%)(p-value-for-interaction=0.03).结论在急诊科可以识别出对脓毒症液体治疗策略有不同反应的亚表型。这些亚表型的鉴定可以为脓毒症诱导的低血压和肾损伤患者提供精确指导的治疗方法。
