Prerenal AKI Definition by BUN/Creatinine and FENa
Prerenal AKI is traditionally defined by FENa <1%, though this has significant limitations with only 14% specificity in some populations, and the BUN/creatinine ratio is not a standard diagnostic criterion in current guidelines.
Fractional Excretion of Sodium (FENa)
Traditional Cutoff Values
- **FENa <1% suggests prerenal causes** including volume depletion, while FENa >1% suggests intrinsic renal causes like acute tubular necrosis (ATN) 1
- In meta-analysis of 15 studies with 872 patients using the 1% threshold, pooled sensitivity was 90% and specificity was 82% for differentiating intrinsic from prerenal AKI 2
Critical Limitations in Clinical Practice
- In cirrhotic patients, FENa <1% had 100% sensitivity but only 14% specificity for diagnosing prerenal causes, making it nearly useless in this population 1
- In patients on diuretics, FENa performance drops dramatically: sensitivity 80% but specificity only 54%, rendering it unreliable 2
- In patients with CKD or on diuretics, pooled sensitivity was 83% and specificity only 66% 2
Optimal Performance Context
- FENa performs best in oliguric patients without CKD or diuretic therapy: sensitivity 95% and specificity 91% 2
- Urine sodium <10 mEq/L typically accompanies low FENa in prerenal states, but may be higher with recent diuretic use 1
Fractional Excretion of Urea (FEUrea)
Alternative Marker
- FEUrea <35% may better discriminate prerenal from intrinsic AKI, particularly because it is not affected by diuretic use 1
- In cirrhotic patients, FEUrea <28.16% showed 75% sensitivity and 83% specificity for separating hepatorenal syndrome from non-HRS 1
Comparative Performance
- In patients not on diuretics, FEUrea at 35% cutoff showed no significant difference compared to FENa at 1%: sensitivity 77% versus 89% (p=0.410) and specificity 80% versus 79% (p=0.956) 3
- In patients on diuretics, FEUrea showed lower sensitivity (52% vs 92%) but higher specificity (82% vs 44%) compared to FENa 3
- Overall meta-analysis found FEUrea >35% had pooled sensitivity of 66% and specificity of 75%, indicating limited utility 3
BUN/Creatinine Ratio
Notable Absence from Guidelines
- The BUN/creatinine ratio is not mentioned as a diagnostic criterion in the 2022 AGA guidelines or 2015 KDIGO definitions for differentiating prerenal from intrinsic AKI 1
- While historically used (ratio >20:1 suggesting prerenal), this parameter has been superseded by more specific urinary indices in modern practice
Practical Diagnostic Algorithm
Step 1: Assess Clinical Context
- Identify if patient is on diuretics, has cirrhosis, or has CKD—these dramatically reduce FENa reliability 1, 2
- Check for oliguria (urine output <0.5 mL/kg/h)—FENa performs best in this setting 2
Step 2: Select Appropriate Urinary Index
- If no diuretics and oliguric: Use FENa <1% (sensitivity 95%, specificity 91%) 2
- If on diuretics: Consider FEUrea <35% for higher specificity (82%), though sensitivity drops to 52% 3
- If cirrhotic: FENa <1% is unreliable; use FEUrea <28.16% or clinical response to albumin challenge 1
Step 3: Integrate with Clinical Response
- In hypovolemic AKI, volume replacement should reduce serum creatinine by ≥0.3 mg/dL toward baseline 1
- Lack of response to fluid challenge despite low FENa suggests intrinsic injury or hepatorenal syndrome 1
Important Caveats
Biomarker Evidence of Injury
- Even "prerenal" AKI shows elevated injury biomarkers (KIM-1, cystatin C, IL-18) in 95% of cases, suggesting it represents mild tubular injury rather than purely functional impairment 4
- This challenges the traditional concept that prerenal AKI is completely reversible without structural damage 4