Abstract: TH-OR11
Molecular Phenotyping of Patients with Sepsis and Kidney Injury and Differential Response to Fluid Therapy: Secondary Analysis of a Clinical Trial
Session Information
- AKI: New Frontiers in Prognostication and Management
October 24, 2024 | Location: Room 6C, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Kiernan, Elizabeth, University of Washington, Seattle, Washington, United States
- Zelnick, Leila R., University of Washington, Seattle, Washington, United States
- Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
- Himmelfarb, Jonathan, University of Washington, Seattle, Washington, United States
- Bhatraju, Pavan K., University of Washington, Seattle, Washington, United States
Group or Team Name
- On behalf of CLOVERS Investigators.
Background
We previously identified AKI sub-phenotypes (SP1 and SP2) characterized by differences in inflammation and endothelial dysfunction. Here we identify these sub-phenotypes in the emergency department and test for differences in treatment response to a restrictive versus liberal fluid strategy in patients with sepsis-induced hypotension in the Crystalloid Liberal or Vasopressors Early in Sepsis (CLOVERS) trial. The original CLOVERS study demonstrated no differences in clinical outcomes between treatment arms or in sub-groups with AKI or ESKD on enrollment.
Methods
We applied latent class analysis methodology to 23 study enrollment variables and applied a previously developed 3-variable 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]).
Results
Among 1289 CLOVERS patients with available plasma, 771 had AKI and 75 had ESKD on enrollment. Latent class analysis identified a two sub-phenotype model as the optimal fit for the data with high correlation to two sub-phenotypes identified with the 3-biomarker model (Cohen’s Kappa 0.8). The model identified 605 as SP1 and 241 as SP2. The risk of 28 and 90-day mortality was greater in SP2 relative to SP1 independent of AKI stage and sequential organ failure assessment 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
Clinically distinct sub-phenotypes can be identified in biospecimens collected in the emergency department and respond differently to fluid strategy in sepsis. This could inform a precision-guided therapeutic approach for patients with sepsis-induced hypotension and kidney injury.