How to interpret and use fractional excretion of urea (FeUrea) in clinical practice?

Fractional Excretion of Urea (FeUrea): Clinical Interpretation and Application

The fractional excretion of urea (FeUrea) is most valuable for differentiating between pre-renal acute kidney injury and acute tubular necrosis, with a cutoff value of <28.16% having a sensitivity of 75% and specificity of 83% for identifying pre-renal causes of AKI, especially in patients receiving diuretics. 1

Calculation and Normal Values

FeUrea is calculated using the following formula:

FeUrea = [(Urine urea × Serum creatinine) / (Serum urea × Urine creatinine)] × 100

Interpretation thresholds:

• FeUrea <28-35%: Suggests pre-renal acute kidney injury
• FeUrea >35%: Suggests intrinsic renal failure/acute tubular necrosis (ATN)

Clinical Applications

1. Differentiating Pre-renal AKI from ATN

FeUrea offers significant advantages over fractional excretion of sodium (FENa) in specific clinical scenarios:

• Patients on diuretics: FeUrea remains reliable even when patients have received diuretic therapy, as urea reabsorption occurs primarily in the proximal tubule and collecting ducts and is not significantly affected by diuretics 1, 2

• Higher specificity in diuretic-treated patients: While FENa has higher sensitivity (92% vs 52%), FeUrea demonstrates superior specificity (82% vs 44%) for diagnosing intrinsic AKI in patients receiving diuretics 3

2. Hepatorenal Syndrome Diagnosis

In patients with cirrhosis and AKI:

• FeUrea <28.16% helps distinguish hepatorenal syndrome (a form of pre-renal AKI) from other causes of kidney injury 1
• This is particularly valuable since FENa has poor specificity (only 14%) despite high sensitivity (100%) for pre-renal causes in cirrhotic patients 1

Limitations and Pitfalls

1. Infection may reduce accuracy: FeUrea may be less reliable in patients with active infections, where FENa might provide more accurate information 4

2. Recent meta-analysis cautions about overall utility: A 2024 systematic review found that FeUrea has limited overall utility in differentiating intrinsic from pre-renal AKI, with pooled sensitivity of 66% and specificity of 75% for a cutoff >35% 3

3. Combined interpretation with FENa may be optimal: In sepsis patients, the combination of high FENa and high FeUrea strongly predicts transient AKI, while high FENa with low FeUrea suggests intrinsic AKI 5

Practical Algorithm for FeUrea Use

1. Collect appropriate samples:

   • Simultaneous blood and urine samples
   • Measure urea and creatinine in both blood and urine

2. Calculate FeUrea using the formula above

3. Interpret based on clinical context:

   • If patient is on diuretics: Prioritize FeUrea over FENa
   • If patient has infection: Consider both FeUrea and FENa
   • If patient has cirrhosis: FeUrea <28.16% suggests hepatorenal syndrome

4. Combine with other parameters:

   • Response to volume challenge (reduction in serum creatinine by 0.3 mg/dL suggests pre-renal cause) 1
   • Urinalysis findings (bland sediment in pre-renal causes)
   • Clinical presentation and risk factors

Special Populations

• Pediatric patients: FeUrea <35% has demonstrated higher sensitivity and specificity than FENa <1% for differentiating pre-renal from intrinsic renal failure in children 6

• Critically ill septic patients: A combination of FENa >0.36% and FeUrea >31.5% has a negative predictive value of 94.5% for transient AKI 5

Remember that FeUrea should be interpreted as part of a comprehensive assessment of kidney function, considering the clinical context and other laboratory parameters, rather than as an isolated diagnostic test.