How is fractional excretion of sodium (FENA) used to differentiate between prerenal and intrinsic renal causes of acute kidney injury (Impaired renal function)?

Fractional Excretion of Sodium (FENa) in Differentiating Prerenal from Intrinsic Acute Kidney Injury

FENa <1% strongly suggests prerenal acute kidney injury, while FENa >1% typically indicates intrinsic renal causes like acute tubular necrosis (ATN) in patients not on diuretics. 1

Calculation and Interpretation of FENa

FENa is calculated using the following formula:

• FENa = [(Urine Na × Serum Cr) / (Serum Na × Urine Cr)] × 100 1

Interpretation guidelines:

• FENa <1%: Strongly suggests prerenal AKI
• FENa >1%: Suggests intrinsic renal causes (particularly ATN)

Diagnostic Accuracy

The diagnostic accuracy of FENa varies significantly based on patient characteristics:

• In oliguric patients without CKD or diuretic therapy, FENa has excellent performance with pooled sensitivity of 95% and specificity of 91% 2
• In the general population, using a threshold of 1%, FENa has a pooled sensitivity of 90% and specificity of 82% for differentiating intrinsic from prerenal AKI 2

Important Limitations and Pitfalls

1. Diuretic therapy: FENa becomes significantly less reliable in patients on diuretics

   • Diuretics increase sodium excretion regardless of underlying cause
   • In patients on diuretics, sensitivity drops to 80% and specificity to only 54% 2

2. Other conditions affecting FENa interpretation:

   • Chronic kidney disease
   • Advanced age
   • Sepsis
   • Contrast nephropathy
   • Urinary tract obstruction
   • Certain glomerulonephritides 1

Alternative: Fractional Excretion of Urea (FEUrea)

When diuretics have been administered, FEUrea may be more reliable than FENa:

• Formula: FEUrea = [(Urine urea × Serum Cr) / (Serum urea × Urine Cr)] × 100 1
• Interpretation:
  • FEUrea <35%: Suggests prerenal AKI
  • FEUrea >35%: Suggests intrinsic renal causes 1

However, recent evidence suggests FEUrea has limitations:

• Overall sensitivity of 66% and specificity of 75% for distinguishing intrinsic from prerenal AKI 3
• In patients on diuretics, FEUrea shows lower sensitivity (52%) but higher specificity (82%) compared to FENa 3

Clinical Application Algorithm

1. Obtain baseline data:

   • Calculate FENa using spot urine and serum samples
   • Document diuretic use
   • Check for conditions that may affect interpretation 1

2. For patients NOT on diuretics:

   • FENa <1%: Diagnose prerenal AKI
   • FENa >1%: Diagnose intrinsic renal cause (likely ATN)

3. For patients on diuretics:

   • Calculate FEUrea
   • FEUrea <35%: Consider prerenal AKI
   • FEUrea >35%: Consider intrinsic renal cause
   • Consider that neither test is perfect in this setting

4. Additional diagnostic steps:

   • Perform urinalysis to examine for hematuria, proteinuria, or abnormal sediment
   • Conduct urine microscopy (muddy brown casts suggest ATN; RBC casts suggest glomerulonephritis)
   • Consider renal ultrasound to evaluate kidney size and rule out obstruction 1

Key Caveats

• Relying solely on FENa when the patient is on diuretics can lead to misdiagnosis 1
• FENa should be interpreted in the context of the complete clinical picture, not in isolation
• In patients with CKD or on diuretics, FENa has limited diagnostic value (sensitivity 83%, specificity 66%) 2
• Overreliance on a single test rather than integrating clinical findings, urinalysis, and other laboratory data can lead to inaccurate diagnosis 1