Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes

作者：Ian B. Stanaway, Eric D. Morrell, F. Linzee Mabrey, Neha A. Sathe, Zoie A. Bailey, Sarah Speckmaier, J.L. Lo, Leila R. Zelnick, Jonathan Himmelfarb, Carmen Mikacenic, Laura Evans, Mark M. Wurfel, Pavan K. Bhatraju · 发表于：Critical Care · 年份：2024 · DOI：10.1186/s13054-024-05202-9 · 被引用次数：17 · 研究领域：Acute Kidney Injury Research、Complement system in diseases、Sepsis Diagnosis and Treatment

BACKGROUND: Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes. METHODS: We prospectively enrolled 173 ICU patients with sepsis from a suspected respiratory infection (87 without AKI and 86 with AKI on enrollment). Among the AKI patients, 66 were classified as AKI-SP1 and 20 as AKI-SP2 using a three-plasma biomarker classifier. Aptamer-based proteomics assessed 5,212 proteins in urine collected on ICU admission. We compared urinary protein abundances between AKI sub-phenotypes, conducted pathway analyses, tested associations with risk of RRT and blood bacteremia, and predicted AKI-SP2 class membership using LASSO. MEASUREMENT AND MAIN RESULTS: In total, 117 urine proteins were higher in AKI-SP2, 195 were higher in AKI-SP1 (FDR < 0.05). Urinary proteins involved in inflammation and chemoattractant of neutrophils and monocytes (CXCL1 and REG3A) and oxidative stress (SOD2) were abundant in AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), proliferation of mesenchymal cells (IL11RA), anti-inflammatory (IL10RB and TREM2) were abundant in AKI-SP1. Pathways related to immune response, complement activation and chemokine signaling we...