Fractional Excretion of Sodium (FeNa) is the Most Appropriate Test
Fractional excretion of sodium (FeNa) is the most reliable and practical test to differentiate pre-renal from intrinsic AKI, with FeNa <1% indicating pre-renal AKI and >1% suggesting intrinsic tubular damage. 1
Why FeNa is Superior to Other Options
Serum Creatinine Levels
- Serum creatinine cannot differentiate between pre-renal and intrinsic AKI—it only confirms the presence of kidney injury but provides no etiological information 2
- Creatinine rises in both pre-renal and intrinsic AKI, making it useless for distinguishing between these entities 3
BUN/Creatinine Ratio
- While a BUN/Cr ratio >20:1 traditionally suggests pre-renal azotemia, this parameter is not mentioned in current guidelines as a reliable differentiating tool 4, 1
- This ratio is confounded by numerous factors including protein intake, GI bleeding, and catabolic states
Urine Specific Gravity
- Urine specific gravity (USG) shows high specificity (>85%) for pre-renal AKI when elevated, but it is less sensitive than FeNa and provides limited information about intrinsic AKI 5
- USG is useful as a complementary parameter but not as the primary differentiating test 5
How to Use FeNa Correctly
Diagnostic Thresholds
- FeNa <1%: Highly suggestive of pre-renal AKI, indicating the kidneys are avidly reabsorbing sodium to preserve intravascular volume 1
- FeNa >1%: Indicates intrinsic tubular damage where the kidneys have lost their ability to reabsorb sodium appropriately 1
- Urine sodium concentration <10 mEq/L typically accompanies pre-renal AKI 1
Important Limitations and Pitfalls
Diuretic Use: FeNa loses reliability in patients receiving loop diuretics, as these medications force sodium excretion regardless of the underlying etiology 1, 3
Sepsis Context: The value of FeNa has been questioned specifically in septic AKI, where pre-renal and intrinsic mechanisms frequently coexist and evolve dynamically 1, 3
Alternative in Diuretic Users: Consider fractional excretion of urea (FEUrea) when diuretics confound FeNa interpretation—FEUrea <35% suggests pre-renal AKI with better performance than FeNa in certain populations 1, 6
Composite Approach for Maximum Accuracy
When FeNa is equivocal or confounded, use a composite biochemical criterion:
- Combine at least two of three parameters: FeNa, urine-to-plasma creatinine ratio (UCr/PCr), and renal failure index (RFI) 7
- Patients with at least two parameters indicating intrinsic AKI should be classified as such; those with at least two pre-renal parameters are classified as pre-renal 7
- This composite approach minimizes distortion from individual confounding factors 7
Additional Confirmatory Tests
Urine Sediment Analysis
- KDIGO guidelines recommend routine urine sediment analysis in all AKI patients for differential diagnosis 1
- Pre-renal AKI shows "bland" sediment (normal or minimal findings) 1
- Intrinsic AKI (ATN) shows muddy brown casts, tubular epithelial cells, and cellular debris 4, 1
Emerging Biomarkers
- Urinary NGAL (neutrophil gelatinase-associated lipocalin) effectively discriminates intrinsic from pre-renal AKI with area under ROC curve of 0.87 2
- NGAL >104 μg/L indicates intrinsic AKI (likelihood ratio 5.97), while <47 μg/L makes intrinsic AKI unlikely (likelihood ratio 0.2) 2
- However, NGAL is not yet widely available in routine clinical practice 1
Critical Clinical Context
The traditional classification of "pre-renal" versus "intrinsic" AKI is increasingly recognized as problematic because these mechanisms frequently coexist, particularly in sepsis. 1, 3 The term "pre-renal" is often misinterpreted as "hypovolemic," which can encourage indiscriminate fluid administration 1, 3. Despite these conceptual limitations, FeNa remains the most practical and validated test for initial differentiation in clinical practice.