What laboratory tests are used in the diagnosis and management of Acute Kidney Injury (AKI)?

Laboratory Tests in Acute Kidney Injury (AKI)

The essential laboratory tests for diagnosing and managing AKI include serum creatinine, blood urea nitrogen (BUN), electrolytes, urinalysis with microscopy, and urine sodium, with newer biomarkers like serum cystatin C, urine NGAL, and KIM-1 showing promise for earlier detection. 1

Core Diagnostic Tests for AKI

Serum Markers

• Serum creatinine: Primary diagnostic marker used to define AKI according to KDIGO criteria 1:

  Stage	Serum Creatinine Criterion	Urine Output Criterion
  1	Increase ≥0.3 mg/dL within 48h or 1.5-1.9 times baseline	<0.5 mL/kg/h for 6-12h
  2	2.0-2.9 times baseline	<0.5 mL/kg/h for ≥12h
  3	≥3.0 times baseline or ≥4.0 mg/dL or RRT initiation	<0.3 mL/kg/h for ≥24h or anuria for ≥12h

• Blood Urea Nitrogen (BUN): Helps assess severity and can indicate pre-renal causes when BUN/creatinine ratio is elevated (>20:1) 2

• Electrolytes: Sodium, potassium, chloride, bicarbonate to assess electrolyte imbalances and acid-base status 1

• Serum cystatin C: More sensitive than creatinine for early AKI detection and less affected by muscle mass 3

Urine Tests

• Urinalysis with microscopy: Essential for identifying the nature and site of kidney injury 2, 4

  • Muddy brown casts suggest acute tubular necrosis
  • RBC casts suggest glomerulonephritis
  • WBC casts suggest interstitial nephritis or pyelonephritis
  • Crystals may indicate drug-induced nephropathy

• Urine sodium (UNa): High specificity (>85%) for differentiating pre-renal AKI (<20 mEq/L) from intrinsic AKI (>40 mEq/L) 4

• Urine specific gravity (USG): High specificity for pre-renal AKI when >1.020 4

• Fractional excretion of sodium (FENa):

  • <1% suggests pre-renal AKI

  • 2% suggests intrinsic AKI/ATN 5, 4

• Fractional excretion of urea (FEUrea): More reliable than FENa in patients on diuretics

  • <35% suggests pre-renal AKI

  • 50% suggests intrinsic AKI 5

• Renal Failure Index (RFI): High specificity for differentiating pre-renal from intrinsic AKI 4

• Urine osmolality: Helps differentiate pre-renal (>500 mOsm/kg) from intrinsic AKI (<350 mOsm/kg) 4

Newer Biomarkers for Early Detection

• Urine NGAL (neutrophil gelatinase-associated lipocalin): Rises 2 hours after kidney injury, well before creatinine 3

• Urine IL-18: Excellent for early diagnosis and mortality prediction 3

• Kidney Injury Molecule-1 (KIM-1): Performs well for established AKI diagnosis and mortality prediction 3

• Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7): Newer biomarkers for risk stratification 6

Monitoring Protocol for AKI

Daily Monitoring

• Daily serum creatinine, BUN, electrolytes, and acid-base status 1
• Fluid balance assessment and daily weights 1
• Hemodynamic parameters monitoring 1

Follow-up Monitoring

• For patients who recover from AKI Stage 1: Primary care follow-up within 3 months 1
• For AKI Stage 2 with recovery: Primary care follow-up within 30 days 1
• For AKI Stage 3 or required RRT: Nephrology follow-up within 1 week of discharge 1
• For persistent kidney dysfunction at discharge: Nephrology follow-up within 30 days 1, 7

Special Considerations in Cirrhosis

In patients with cirrhosis, the International Club of Ascites recommends specific diagnostic criteria for AKI 5:

• Increase in serum creatinine ≥0.3 mg/dL (26.5 μmol/L) within 48h; or
• Increase in serum creatinine ≥50% from baseline which occurred within the prior 7 days

The baseline serum creatinine should be a value obtained in the previous 3 months when available. If multiple values exist, use the one closest to admission 5.

Common Pitfalls to Avoid

• Relying solely on serum creatinine: Creatinine is a late marker of AKI and overestimates GFR in patients with cirrhosis due to muscle wasting, increased tubular secretion, and dilution from increased volume of distribution 5

• Neglecting urine microscopy: Simple but powerful diagnostic tool that is often underutilized 2

• Inadequate follow-up monitoring: Only 12% of AKI patients receive recommended proteinuria assessment within one year 7

• Ignoring the impact of medications: Loop diuretics can affect FENa interpretation (use FEUrea instead) 4

• Failing to establish accurate baseline creatinine: Critical for proper AKI diagnosis and staging 5

By systematically applying these laboratory tests and following established monitoring protocols, clinicians can improve early detection, appropriate management, and follow-up care for patients with AKI, ultimately reducing morbidity and mortality.