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Abstract: TH-OR10

Novel Urinary Proteins Differentiate Sub-Phenotypes in Patients With Sepsis-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical‚ Outcomes‚ and Trials

Authors

  • Stanaway, Ian Byrell, University of Washington School of Medicine, Seattle, Washington, United States
  • Thau, Matthew R., University of Washington School of Medicine, Seattle, Washington, United States
  • Zelnick, Leila R., University of Washington School of Medicine, Seattle, Washington, United States
  • Morrell, Eric D., University of Washington School of Medicine, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington School of Medicine, Seattle, Washington, United States
  • Wurfel, Mark M., University of Washington School of Medicine, Seattle, Washington, United States
  • Bhatraju, Pavan K., University of Washington School of Medicine, Seattle, Washington, United States
Background

Patients with sepsis-induced AKI can be classified into distinct sub-phenotypes (AKI-SP1 and AKI-SP2) using biomarkers of inflammation and endothelial dysfunction. These sub-phenotypes differ in clinical outcomes and treatment response, though biologic mechanisms underlying these sub-phenotypes remain unknown.

Methods

We prospectively enrolled 120 ICU patients with suspected infection (including COVID-19), both with AKI (n=62) and without (n=58), collecting matched blood and urine within 24 hours of ICU admission. We classified patients with AKI as AKI-SP1 (n=45) or AKI-SP2 (n=17) using three plasma biomarkers: angiopoietin-1, angiopoietin-2 and soluble tumor necrosis factor receptor 1. Using the SomaScan ® platform to measure 5,212 urinary proteins, we compared urinary proteins in patients with and without AKI and between patients with AKI-SP1 and AKI-SP2, adjusting for age, sex, BMI, and COVID infection using a false discovery rate (FDR) < 0.05.

Results

AKI-SP2 had higher risk for new dialysis (OR=12.2; 95% CI: 2.0-73.1; p=0.006) compared to AKI-SP1, adjusting for age, sex, BMI, and COVID infection. No urinary proteins were differentially expressed in patients with and without AKI (Figure 1A). In patients with AKI, 194 proteins were significantly higher in the urine in AKI-SP2, and 296 proteins were higher in AKI-SP1 (Figure 1B). Proteins involved in inflammation, chemoattraction of neutrophils and monocytes (CXCL1 and CCL14) and oxidative stress (SOD2) were associated with AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), and mesenchymal cell proliferation (IL11RA) were associated with AKI-SP1.

Conclusion

In patients with sepsis-induced AKI, we identified 490 urinary proteins that differed significantly between two AKI sub-phenotypes. The alternative functions of these proteins suggest heterogeneity in the pathophysiology that drives AKI in sepsis and supports the value of AKI sub-phenotypes for the identification of novel pathways in AKI development.

Funding

  • NIDDK Support