Molecular Phenotyping of Patients with Sepsis and Kidney Injury and Differential Response to Fluid Resuscitation.

Autor:	Kiernan E; UW: University of Washington., Zelnick LR; University of Washington., Khader A; University of Washington., Coston TD; University of Washington., Bailey ZA; University of Washington., Speckmaier S; University of Washington., Lo J; University of Washington., Sathe N; University of Washington., Kestenbaum BR; University of Washington., Himmelfarb J; University of Washington., Johnson N; University of Washington., Shapiro N; Harvard Medical School., Douglas IS; Denver Health Main Campus., Hough C; Oregon Health & Science University., Bhatraju P; University of Washington.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Jul 02. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.21203/rs.3.rs-4523416/v1
Abstrakt:	Purpose: 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. Methods: 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. Results: 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). Conclusion: 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.
Databáze:	MEDLINE
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