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

Using Fractional Excretion of Sodium (FENa) to Differentiate Prerenal from Intrinsic Renal Causes of AKI

FENa <1% strongly suggests prerenal acute kidney injury, while FENa >1% typically indicates intrinsic renal causes like acute tubular necrosis (ATN), though this parameter has important limitations especially in patients on diuretics. 1

Understanding FENa

FENa is a calculated value that measures the percentage of filtered sodium that is excreted in the urine:

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

Interpretation of FENa Values:

• FENa <1%: Suggests prerenal causes (volume depletion, decreased cardiac output, etc.)
• FENa >1%: Suggests intrinsic renal causes, particularly ATN 1

Diagnostic Performance

The diagnostic accuracy of FENa varies based on clinical context:

• In patients without CKD or diuretic therapy who are oliguric, FENa has excellent performance:

  • Sensitivity: 95%
  • Specificity: 91% 2

• In general populations, FENa at 1% threshold shows:

  • Sensitivity: 90%
  • Specificity: 82% 2

Important Limitations

1. Diuretic Use: FENa loses reliability in patients on diuretics as these medications increase sodium excretion regardless of volume status

   • In patients on diuretics, specificity drops to 54% 2
   • A FENa <1% had a sensitivity of 100% but a specificity of only 14% for prerenal causes in cirrhotic patients 1

2. Other Conditions Affecting FENa:

   • 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

• Interpretation:

  • FEUrea <35% suggests prerenal AKI
  • FEUrea >35% suggests intrinsic renal causes 3

• In cirrhotic patients, FEUrea <28.16% had:

  • Sensitivity: 75%
  • Specificity: 83% for identifying prerenal causes 1, 3

• FEUrea is less affected by diuretics because urea reabsorption occurs primarily in the proximal tubule and collecting ducts through passive mechanisms 4

Clinical Algorithm for Using FENa in AKI Diagnosis

1. Obtain baseline data:

   • Calculate FENa using spot urine and serum samples
   • Document diuretic use in past 24 hours
   • Check for conditions that may affect interpretation

2. Interpret results based on clinical context:

   • If patient is NOT on diuretics:

     • FENa <1%: Likely prerenal AKI → Trial of volume repletion
     • FENa >1%: Likely intrinsic renal cause → Further workup for ATN, glomerulonephritis, etc.

   • If patient IS on diuretics:

     • Calculate FEUrea instead
     • FEUrea <35%: Likely prerenal AKI
     • FEUrea >35%: Likely intrinsic renal cause

3. Response to volume challenge:

   • In prerenal AKI, volume replacement should reduce serum creatinine by 0.3 mg/dL from baseline 1
   • Lack of response suggests intrinsic renal cause or ongoing injury

Additional Diagnostic Considerations

• Urinalysis: Examine for hematuria, proteinuria, or abnormal sediment (suggests intrinsic renal disease) 1
• Urine microscopy: Muddy brown casts suggest ATN; RBC casts suggest glomerulonephritis
• Renal ultrasound: Normal kidney size suggests AKI rather than CKD; evaluate for obstruction 1

Pitfalls to Avoid

1. Relying solely on FENa when patient is on diuretics
2. Using traditional "prerenal" and "renal" terminology which may lead to inappropriate fluid administration 1
3. Failing to consider the clinical context when interpreting FENa results
4. Not recognizing that FENa may be falsely elevated in patients with bicarbonaturia, glycosuria, or certain medications
5. Overreliance on a single test rather than integrating clinical findings, urinalysis, and other laboratory data

Remember that while FENa and FEUrea are useful diagnostic tools, they should be interpreted within the broader clinical context of the patient's presentation, and no single test should be used in isolation to determine AKI etiology.