Utility of Biomarkers for Sepsis-Associated Acute Kidney Injury Staging

Area of Science:

• Nephrology and Critical Care Medicine
• Biomarker Discovery and Validation
• Translational Research in Acute Illness

Background:

• The 23rd Acute Disease Quality Initiative (ADQI-23) proposed integrating biomarkers into acute kidney injury (AKI) staging.
• The utility of tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) for AKI staging remains uncertain.

Purpose of the Study:

• To investigate the association between elevated urinary [TIMP-2] × [IGFBP7] levels and reduced survival in patients with AKI.
• To determine if these biomarkers can refine the staging of AKI.

Main Methods:

• A cohort study utilizing data from the Protocolized Care for Early Septic Shock (ProCESS) trial.
• Patients with septic shock were analyzed, excluding those with end-stage kidney disease or missing creatinine/biomarker data.
• Urinary [TIMP-2] × [IGFBP7] levels were measured, with a cutoff of 2.0 (ng/mL)²/1000 used to define biomarker-positive/negative status.

Main Results:

• In 999 patients, higher urinary [TIMP-2] × [IGFBP7] levels were associated with significantly lower 30-day survival across AKI stages 1, 2, and 3.
• The association between biomarker positivity and reduced survival was specific to patients with AKI.
• No significant difference in survival was observed between biomarker-positive and negative patients without functional AKI criteria.

Conclusions:

• The cell-cycle arrest biomarkers TIMP-2 and IGFBP7 show potential to enhance AKI staging in patients with functional AKI criteria.
• These findings support the integration of [TIMP-2] × [IGFBP7] into clinical practice for improved AKI patient management.