Kidney Week

Abstract: TH-OR10

Complementary Role of Transcriptomic Endotyping and Protein-Based Biomarkers for Risk Stratification in Sepsis-Associated AKI

Session Information

• AKI: New Frontiers in Prognostication and Management
  October 24, 2024 | Location: Room 6C, Convention Center
  Abstract Time: 04:30 PM - 04:40 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Nusshag, Christian, Heidelberg University Hospital, Department of Nephrology, Heidelberg, Baden-Wuerttemberg, Germany

Christian Nusshag, MD, DrMed

• Tavris, Bengi Su, Heidelberg University Hospital, Department of Nephrology, Heidelberg, Baden-Wuerttemberg, Germany

Bengi Su Tavris, MD

• Morath, Christian, Heidelberg University Hospital, Department of Nephrology, Heidelberg, Baden-Wuerttemberg, Germany

Christian Morath, MD

• Uhle, Florian, University Hospital Heidelberg, Department of Anesthesiology, Heidelberg, Baden-Wuerttemberg, Germany

Florian Uhle, PhD

• Sweeney, Timothy, Inflammatix Inc, Burlingame, California, United States

Timothy Sweeney, MD, PhD

• Liesenfeld, Oliver S., Inflammatix Inc, Burlingame, California, United States

Oliver S. Liesenfeld, MD

• Fiedler-Kalenka, Mascha Onida, University Hospital Heidelberg, Department of Anesthesiology, Heidelberg, Baden-Wuerttemberg, Germany

Mascha Onida Fiedler-Kalenka

• Brenner, Thorsten, University Hospital Essen, Department of Anesthesiology, Essen, Nordrhein-Westfalen, Germany

Thorsten Brenner, MD, PhD

• Zeier, Martin G., Heidelberg University Hospital, Department of Nephrology, Heidelberg, Baden-Wuerttemberg, Germany

Martin G. Zeier, MD, FASN

• Weigand, Markus A., University Hospital Heidelberg, Department of Anesthesiology, Heidelberg, Baden-Wuerttemberg, Germany

Markus A. Weigand

Group or Team Name

• Nusshag Lab.

Background

Sepsis-associated acute kidney injury (SA-AKI) is the most common form of AKI in critically ill patients. Heterogeneous immune responses in sepsis contribute to the failure of uniform treatment strategies. Transcriptomic endotyping (TE) may identify septic patients with common pathophysiological drivers, enhancing risk stratification and outcome prediction. This study evaluated TE's clinical value in predicting kidney-related outcomes and its complementary role with protein-based biomarkers.

Methods

ICU patients meeting Sepsis-3 criteria were assigned to inflammopathic (IE), adaptive (AE), or coagulopathic endotype (CE) using a gene expression-based classifier. Baseline measurements included SCr, CysC, PENK, NGAL, KIM-1, suPAR, and BioADM in blood, and TIMP2*IGFBP7 in urine. Clinical outcomes were tracked for 30 days.

Results

From 167 sepsis patients, 33% were classified as IE, 42% as AE, and 24% as CE. IE was associated with the worst outcomes, including higher seven-day mortality, need for renal replacement therapy (RRT), sepsis scores, and septic shock incidence (Figure 1). Baseline NGAL and suPAR, both related to immune activation and inflammation, were highest in IE. SCr and CysC for AE; NGAL, suPAR, and TIMP2*IGFBP7 for IE; and BioADM for CE best stratified RRT or death within seven days of sepsis diagnosis. Combining TE with functional and inflammation-related markers significantly improved outcome prediction. The combination of PENK, BioADM, and TE best predicted RRT or death within seven days with an AUC of 0.84.

Conclusion

TE enhances risk stratification and predictive enrichment in sepsis patients, improving the clinical validity of protein-based biomarkers for specific endotypes. This supports a more individualized approach to managing SA-AKI, with distinct biomarker patterns reflecting different pathophysiological mechanisms.