Identification of Acute Kidney Injury Subphenotypes with Differing Molecular Signatures and Responses to Vasopressin Therapy

作者：Pavan K. Bhatraju, Leila R. Zelnick, Jerald R. Herting, Ronit Katz, Carmen Mikacenic, Susanna Kosamo, Eric D. Morrell, Cassianne Robinson‐Cohen, Carolyn S. Calfee, Jason D. Christie, Kathleen D. Liu, Michael A. Matthay, William O. Hahn, Victoria Dmyterko, Natalie S. J. Slivinski, Jim Russell, Keith R. Walley, David C. Christiani, W. Conrad Liles, Jonathan Himmelfarb, Mark M. Wurfel · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2018 · DOI：10.1164/rccm.201807-1346oc · 被引用次数：217 · 研究领域：Acute Kidney Injury Research、Sepsis Diagnosis and Treatment、Trauma, Hemostasis, Coagulopathy, Resuscitation

RATIONALE: Currently, no safe and effective pharmacologic interventions exist for acute kidney injury (AKI). One reason may be that heterogeneity exists within the AKI population, thereby hampering the identification of specific pathophysiologic pathways and therapeutic targets. OBJECTIVE: The aim of this study was to identify and test whether AKI subphenotypes have prognostic and therapeutic implications. METHODS: First, latent class analysis methodology was applied independently in two critically ill populations (discovery [n = 794] and replication [n = 425]) with AKI. Second, a parsimonious classification model was developed to identify AKI subphenotypes. Third, the classification model was applied to patients with AKI in VASST (Vasopressin and Septic Shock Trial; n = 271), and differences in treatment response were determined. In all three populations, AKI was defined using serum creatinine and urine output. MEASUREMENTS AND MAIN RESULTS: A two-subphenotype latent class analysis model had the best fit in both the discovery (P = 0.004) and replication (P = 0.004) AKI groups. The risk of 7-day renal nonrecovery and 28-day mortality was greater with AKI subphenotype 2 (AKI-SP2) relative to AKI subphenotype 1 (AKI-SP1). The AKI subphenotypes discriminated risk for poor clinical outcomes better than the Kidney Disease: Improving Global Outcomes stages of AKI. A three-variable model that included markers of endothelial dysfunction and inflammation accurately determined subpheno...