What is the utility of the excreted fraction of urea (Urea Excretion Fraction) in assessing kidney function, particularly in acute kidney injury (AKI) or chronic kidney disease (CKD)?

Utility of Excreted Fraction of Urea in Kidney Function Assessment

The fractional excretion of urea (FEUrea) is a more reliable diagnostic tool than fractional excretion of sodium (FENA) for differentiating pre-renal from intrinsic causes of acute kidney injury, particularly in patients receiving diuretics. 1

Definition and Calculation

FEUrea is calculated using the following formula:

• FEUrea = [(Urine urea × Serum creatinine) / (Serum urea × Urine creatinine)] × 100 1

Clinical Utility in AKI Assessment

Advantages over FENA

• FENA has poor specificity (only 14%) despite high sensitivity (100%) for pre-renal causes 1
• FEUrea remains reliable even when patients are on diuretics, which significantly alter sodium handling 1
• FEUrea <28.16% has a sensitivity of 75% and specificity of 83% for identifying pre-renal causes 1, 2

Diagnostic Performance

• FEUrea <40% is a sensitive and specific index for differentiating transient from persistent AKI in ICU patients 3
• In cirrhotic patients, FEUrea helps distinguish between different AKI phenotypes, though recent evidence suggests FENA may be superior in this specific population 4

Interpretation Guidelines

1. Pre-renal AKI:

   • FEUrea <35% strongly suggests pre-renal etiology 1
   • When combined with low FENA (<1%), provides stronger evidence for pre-renal causes 1

2. Intrinsic/Persistent AKI:

   • FEUrea >40% suggests intrinsic or persistent kidney injury 3
   • High FEUrea with high FENA provides strong evidence for intrinsic renal failure 1

3. Response to Treatment:

   • In true pre-renal states, serum creatinine should decrease to within 0.3 mg/dL of baseline after appropriate volume replacement 1
   • FEUrea gradually increases from days 1-7 in transient AKI while plasma creatinine decreases 3

Special Clinical Scenarios

Patients on Diuretics

• FEUrea is the only predictive index of transient AKI in patients receiving diuretic therapy 3
• Traditional FENA becomes unreliable due to altered sodium handling 1, 2

Hepatorenal Syndrome

• FEUrea is more reliable than FENA in patients with hepatorenal syndrome 1
• However, recent evidence suggests FENA with a lower cutoff may actually perform better in cirrhotic patients 4

Monitoring Dialysis Adequacy

• Urea reduction ratio (URR) strongly correlates with Kt/V in assessing dialysis adequacy 5
• Targeting URR ≥0.67 provides a simplified means of assessing adequacy of intermittent hemodialysis in AKI patients 5

Prognostic Value

• Greater magnitude of urea reduction ratio (UXR) is associated with improved patient survival in AKI 6
• Patients achieving UXR >50% demonstrate the best survival (94.3%), while those with 0% UXR have the highest mortality (72.1%) 6
• After adjusting for confounding factors, 10-day mortality is higher in groups that do not achieve UXR of at least 25% 6

Limitations and Caveats

• FEUrea interpretation should be part of a comprehensive assessment including clinical context and other biomarkers 7
• Current tools and diagnostics remain insufficient to accurately assess kidney function in patients receiving acute renal replacement therapy 7
• Alternative approaches for estimating GFR, such as kinetic GFR and the Jelliffe equation, need further evaluation 7

Practice Recommendations

1. Use FEUrea as first-line diagnostic index when differentiating pre-renal from intrinsic AKI, especially in patients on diuretics
2. Apply cutoff of <40% to identify transient/pre-renal AKI
3. Monitor trends in FEUrea over time rather than relying on single measurements
4. Consider UXR monitoring in AKI patients to assess prognosis, with UXR >25% associated with better outcomes
5. In dialysis patients, use URR ≥0.67 as a simplified method to assess adequacy of intermittent hemodialysis