What is the furosemide challenge test (furosemide stress test) and how is it used to predict progression in early-stage acute kidney injury?

What is the Furosemide Stress Test?

The furosemide stress test (FST) is a functional biomarker that assesses tubular responsiveness by measuring urine output after a standardized dose of intravenous furosemide, used to predict progression to severe AKI (stage 3) and the need for renal replacement therapy in patients with early-stage acute kidney injury. 1

Test Protocol and Administration

• Administer 1.0 mg/kg IV furosemide for loop diuretic-naïve patients, or 1.5 mg/kg for patients previously exposed to loop diuretics 2, 3
• Measure hourly urine output for 6 hours following administration 4
• The 2-hour urine output is the most predictive timepoint for risk stratification 2, 3
• Ensure adequate intravascular volume before performing the test, as hypovolemia will confound results 1

Interpretation of Results

Critical Threshold

• Urine output <200 mL in the first 2 hours predicts progression to stage 3 AKI with high accuracy (sensitivity 73.9%, specificity 90.0%, AUC 0.87) 2
• A 2-hour urine output >2 mL/kg indicates furosemide responsiveness and lower risk of progression 4

Predictive Performance

• The FST predicts stage 3 AKI with AUC values of 0.87-0.93 1, 4, 2
• The FST predicts need for renal replacement therapy with AUC values of 0.76-0.96 1, 4, 3
• FST outperforms biochemical biomarkers including NGAL, PENK, and TIMP-2 × IGFBP7 for predicting AKI progression 4, 3

Clinical Applications

Risk Stratification in Early AKI

• Use the FST in patients with AKI stage 1 or 2 to identify those at high risk for progression 1, 2
• For patients with urine output <200 mL in first 2 hours: anticipate progression to stage 3 AKI, intensify monitoring, and prepare for potential RRT 1
• Consider early nephrology consultation for RRT planning in patients with high-risk FST results 1

Integration with Biomarkers

• Combining FST with elevated plasma NGAL levels (>142 ng/mL) improves risk stratification (AUC 0.90 for stage 3 progression, AUC 0.91 for RRT need) 5, 3
• When biomarkers indicate kidney stress, FST provides functional assessment of tubular reserve 6, 1
• The FST should be integrated with all available clinical information, not used as the sole criterion for clinical decisions 1

Predicting RRT Discontinuation

• The FST can predict successful discontinuation of continuous RRT in patients with established AKI (AUC 0.84) 1
• Consider performing FST before attempting CRRT discontinuation in non-septic patients with AKI 1

Post-Transplant Application

• In deceased donor kidney transplantation, intraoperative FST predicts delayed graft function with AUC 0.85 7
• Urine output <600 mL at 6 hours post-furosemide has 83% sensitivity and 74% specificity for delayed graft function 7

Critical Contraindications

Absolute Contraindications

• Do not perform FST in patients with cirrhosis and new-onset AKI—furosemide should be withdrawn immediately in this population 6, 1
• Do not perform FST in hemodynamically unstable patients, as it may precipitate volume depletion, hypotension, and further renal hypoperfusion 1

Relative Contraindications

• Avoid in patients with severe volume depletion until euvolemia is restored 1
• Use caution in patients already receiving high-dose loop diuretics 2

Monitoring Requirements

During and After FST

• Monitor electrolytes every 12-24 hours during IV diuretic therapy 1
• Perform daily renal function assessment (serum creatinine, BUN) 1
• Reassess volume status after the test to detect excessive diuresis 1
• Watch for electrolyte abnormalities, particularly hypokalemia and hypomagnesemia 1

Integration with KDIGO Guidelines

• KDIGO 2020 recommends that a standardized FST may be considered in AKI to quantify the probability of progression, but the result must be integrated with all other clinical information 1
• Biomarkers alone, including FST, are not recommended for deciding to start RRT 1
• Initiate RRT when metabolic and volume demands exceed residual renal capacity, not based solely on FST results 1
• The FST helps quantify residual renal capacity, but final RRT decisions must incorporate overall clinical context, AKI trajectory, comorbidities, and patient care goals 1

Pediatric Considerations

• In critically ill children, FST using 1 mg/kg furosemide predicts stage 3 AKI with AUC 0.93 and need for kidney support therapy with AUC 0.96 4
• The same 2-hour urine output threshold (>2 mL/kg) defines furosemide responsiveness in children 4
• Further research is needed to identify optimal FST cut-offs specific to pediatric populations 4

Common Pitfalls

• Do not use FST as the sole criterion to initiate RRT in euvolemic patients without absolute indications 1
• Recognize that furosemide itself is nephrotoxic—each nephrotoxic medication increases AKI odds by 53% 1
• Variable furosemide dosing in clinical practice can affect interpretation, though studies show FR maintains predictive value across different doses when combined with biomarkers 5
• The FST assesses tubular function and reserve, not glomerular filtration—interpret in context of overall renal physiology 6, 1