How can I incorporate biomarkers into my daily ICU routine for early detection and management of Acute Kidney Injury (AKI)?

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Last updated: September 22, 2025 • View editorial policy

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Incorporating AKI Biomarkers into Daily ICU Practice

The most effective approach to incorporate biomarkers for AKI in your daily ICU routine is to use a combination of damage and functional biomarkers alongside clinical assessment to identify high-risk patients, improve diagnostic accuracy, and guide management decisions. 1

Types of Biomarkers for AKI Detection

Functional Biomarkers

  • Traditional markers: Serum creatinine and urine output (limited by delayed changes)
  • Newer functional markers:
    • Cystatin C (earlier detection than creatinine)
    • Proenkephalin A (reflects GFR changes)

Damage/Stress Biomarkers

  • TIMP-2 × IGFBP7 (urinary): Indicates cellular stress and early damage
  • NGAL (urinary/plasma): Released after tubular damage
  • KIM-1 (urinary): Specific for proximal tubular injury
  • IL-18 (urinary): Inflammatory marker of kidney injury

Practical Implementation Algorithm

1. Risk Assessment and Early Detection

  • Identify high-risk patients using clinical factors plus small changes in serum creatinine (0.1-0.4 mg/dL) 2
  • For high-risk patients (cardiac surgery, sepsis, nephrotoxic medications):
    • Measure TIMP-2 × IGFBP7 (cutoff >0.3 (ng/mL)²/1000) 1
    • Consider NGAL for earlier detection than creatinine

2. Diagnosis and Staging

  • When AKI is suspected or detected by traditional criteria:
    • Combine functional markers (creatinine/cystatin C) with damage markers (TIMP-2 × IGFBP7, NGAL)
    • Use the enhanced AKI staging system incorporating biomarkers 1:
      • Stage 1S: No change in creatinine but biomarker positive
      • Stage 1A: Meets KDIGO criteria but biomarker negative
      • Stage 1B: Meets KDIGO criteria and biomarker positive
      • Similar pattern for stages 2 and 3

3. Management Guidance

  • For biomarker-positive patients:
    • Implement AKI bundle: discontinue nephrotoxins, optimize hemodynamics, avoid hyperglycemia
    • Consider furosemide stress test (FST) for patients with early AKI to predict progression 1
    • Serial biomarker measurements to track response to interventions

4. Predicting Need for Kidney Replacement Therapy (KRT)

  • Combine clinical assessment with biomarkers to predict KRT need:
    • TIMP-2 × IGFBP7 >0.3 (ng/mL)²/1000 associated with increased risk of KRT (HR 2.16) 1
    • Plasma NGAL (AUROC 0.76) and urinary NGAL (AUROC 0.72) 1
    • Cystatin C at KRT discontinuation predicts chronic dialysis need 1

5. Recovery and Prognosis Assessment

  • Monitor biomarkers at ICU discharge to identify patients at risk for progression to chronic kidney disease:
    • Persistent elevation of damage biomarkers despite normalization of creatinine indicates subclinical injury 1
    • Consider nephrology follow-up for patients with persistent biomarker elevation

Practical Implementation Tips

  1. Start with available biomarkers: Begin with what's available at your institution (often NGAL or TIMP-2 × IGFBP7)

  2. Establish local protocols: Create standardized protocols for when to measure biomarkers and how to respond to results

  3. Interpret in clinical context: Always interpret biomarker results in conjunction with clinical assessment and traditional markers

  4. Serial measurements: Single measurements are less useful than trends over time

  5. Combine biomarkers: Using multiple biomarkers improves diagnostic accuracy compared to single biomarkers 1, 3

Common Pitfalls and Limitations

  • Biomarker confounders: Many biomarkers are affected by comorbidities, medications, and inflammatory states

    • NGAL can be elevated in sepsis even without AKI
    • Cystatin C is affected by thyroid dysfunction and corticosteroids

  • Timing matters: Different biomarkers peak at different times after injury

    • TIMP-2 × IGFBP7: 12-24 hours
    • NGAL: 6-12 hours
    • KIM-1: 12-24 hours

  • Cost considerations: Implement a tiered approach, reserving biomarker testing for high-risk patients or those with equivocal clinical presentation

  • Variable cutoff values: Different studies use different thresholds, making standardization difficult 4, 5

  • Limited evidence for intervention: While biomarkers improve early detection, evidence that this translates to improved outcomes remains limited 6

By systematically incorporating these biomarkers into your daily ICU practice, you can enhance early detection of AKI, improve risk stratification, and potentially guide more timely and appropriate interventions to reduce morbidity and mortality associated with AKI.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Acute Kidney Injury Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2013

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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