Kidney Week

Abstract: FR-OR65

Association of Urinary CCL14 with Host-Response and Outcomes in Critically Ill Sepsis Patients with Persistent AKI

Session Information

• Innovative AKI Strategies and Drug Discoveries
  October 25, 2024 | Location: Room 7, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Steenvoorden, Thei Sybe, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Thei Sybe Steenvoorden, MD, MSc

• Vogt, Liffert, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Liffert Vogt, MD, PhD

• Bemelman, Frederike J., Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Frederike J. Bemelman, MD, PhD

• Schultz, Marcus, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Marcus Schultz, PhD

• van der Poll, Tom, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Tom van der Poll, MD, MSc, PhD

• Peters-Sengers, Hessel, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands

Hessel Peters-Sengers, MS, PhD

Background

Urinary concentrations of CC chemokine ligand 14 (CCL14) have recently been identified as a strong predictor of acute kidney injury (AKI) persistence. Whether CCL14 plays a role in the pathogenesis of AKI is still unknown. We postulated that looking at the host-response could help determine a correlation of CCL14 with specific AKI pathophysiologic pathways.

Methods

Critically ill patients with sepsis associated (SA) AKI were included from the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) prospective cohort (N=92). They were grouped by high (>1.3ng/ml) and low CCL14. Plasma levels of 15 biomarkers reflective of: systemic inflammation and cytokine responses, endothelial cell activation, and coagulation activation were quantified. In a subset of 24 SA-AKI patients, whole-blood leukocyte genome-wide transcriptomes were determined.

Results

High CCL14 (n=26, 28.3%) was associated with more severe and persistent renal injury, skin and urinary tract infections compared with low CCL14 (n= 66, 71.7%). Adjusted for disesease severity, age and source of infection High CCL14 was associated with endothelial barrier dysfunction and platelet use (Figure), but also with a heightened transcription of neutrophil degranulation pathways, a dampened response in interferon signaling pathways, upregulated cellular stress response pathways, and a net upregulation of leukocyte activation pathways.

Conclusion

These findings suggest that urinary CCL14 can be used to distinguish a specific subtype of severe AKI with more prominent endothelial activation and barrier disruption, and might be a useful guide for future therapeutic strategies.

Differences in plasma markers of endothelial activation and coagulation in plasma of AKI patients with high (orange) and low (green) urinary CCL14.

Funding

• Private Foundation Support