In an adult patient with an acute rise in serum creatinine, which test best differentiates pre‑renal acute kidney injury from intrinsic acute kidney injury: urine specific gravity, serum creatinine level, fractional excretion of sodium (FeNa), or BUN/creatinine ratio?

Fractional Excretion of Sodium (FENa) Best Differentiates Pre-renal from Intrinsic AKI

Fractional excretion of sodium (FENa) is the most reliable test among the options listed to differentiate pre-renal AKI from intrinsic AKI, with FENa <1% indicating pre-renal causes and FENa >1% suggesting intrinsic renal damage such as acute tubular necrosis. 1, 2

Why FENa is the Preferred Test

Physiologic Basis

• FENa directly assesses the kidney's sodium handling capacity, which reflects tubular function and the kidney's response to decreased perfusion 2
• In pre-renal AKI, the tubules remain intact and appropriately reabsorb sodium in response to decreased renal perfusion, resulting in FENa <1% 1
• In intrinsic AKI (particularly acute tubular necrosis), damaged tubular cells cannot reabsorb sodium effectively, leading to FENa >1% 2

Diagnostic Performance

• FENa <1% has 100% sensitivity for pre-renal causes, though specificity is limited at only 14% in certain populations like cirrhosis 1
• FENa >1% strongly suggests structural kidney damage such as acute tubular necrosis 2
• A recent meta-analysis of 915 patients found FENa maintains reasonable diagnostic utility across diverse clinical settings 3

Why Other Tests Are Less Useful

Serum Creatinine Levels

• Serum creatinine only confirms the presence of AKI but provides no etiological differentiation between pre-renal and intrinsic causes 4
• Creatinine is affected by hydration status, muscle mass, and volume expansion, making it unreliable for determining AKI etiology 4

BUN/Creatinine Ratio

• The BUN:Cr ratio is heavily influenced by non-renal factors including protein intake, gastrointestinal bleeding, corticosteroid use, and catabolic states 1
• While a ratio >20:1 classically suggests pre-renal azotemia, this finding lacks specificity and is easily confounded 1
• The ratio provides supportive but not definitive diagnostic information 1

Urine Specific Gravity

• Urine specific gravity has high specificity (>85%) for pre-renal AKI but is not as quantitative or standardized as FENa 5
• While useful as a bedside parameter, it lacks the precision and validated cutoff values that FENa provides 5

Critical Caveats When Using FENa

Diuretic Use

• Patients receiving loop diuretics can have falsely elevated FENa despite true pre-renal AKI, as diuretics directly impair tubular sodium reabsorption 1, 3
• In diuretic-treated patients, consider fractional excretion of urea (FEUrea) with a cutoff of <35%, which maintains better diagnostic accuracy 3, 6, 7
• FEUrea demonstrated 75% sensitivity and 83% specificity for hepatorenal syndrome versus other AKI causes 1

Special Populations

• In cirrhosis with ascites, FENa <1% has perfect sensitivity but poor specificity (14%) because many intrinsic kidney diseases in cirrhotic patients also present with low FENa 1
• In these patients, FEUrea <28% provides better discrimination (75% sensitivity, 83% specificity) 1

Clinical Context Matters

• FENa must be interpreted alongside clinical assessment of volume status, medication review, and urine sediment analysis 1, 2
• Muddy brown granular casts on urinalysis are pathognomonic for acute tubular necrosis and definitively establish intrinsic AKI regardless of FENa 1

Practical Algorithm for Differentiation

1. Calculate FENa using spot urine and serum samples: FENa = (Urine Na × Serum Cr) / (Serum Na × Urine Cr) × 100 2

2. Interpret based on diuretic exposure:

   • If no recent diuretics: FENa <1% = pre-renal; FENa >1% = intrinsic 1, 2
   • If on diuretics: Calculate FEUrea; <35% = pre-renal; >35% = intrinsic 3, 6, 7

3. Examine urine sediment to confirm or refute the FENa interpretation 1

   • Muddy brown casts = intrinsic AKI (acute tubular necrosis)
   • Bland sediment supports pre-renal diagnosis

4. Assess response to volume challenge if pre-renal AKI suspected: improvement in creatinine with albumin 1 g/kg/day for 2 days confirms diagnosis 1