What is the purpose and protocol of a furosemide (Lasix) stress test in assessing renal function in patients with acute kidney injury (AKI) or impaired renal function?

Furosemide Stress Test in Acute Kidney Injury

Purpose and Clinical Utility

The furosemide stress test (FST) is a functional biomarker used to predict progression to severe AKI (stage 3) and the need for renal replacement therapy (RRT) in patients with early-stage AKI. 1 This test should be considered for risk stratification in critically ill patients with stage 1 or 2 AKI, though it was not included in the original 2012 KDIGO guidelines and requires careful standardization. 1

Key Clinical Applications

The FST serves three primary purposes:

• Predicting progression to stage 3 AKI in patients with early-stage disease, with area under the curve (AUC) values of 0.87-0.93 for this outcome 2, 3
• Identifying patients who will require RRT, with AUC values of 0.76-0.96 for predicting dialysis need 1, 3
• Predicting successful discontinuation of continuous RRT in patients with established AKI (AUC = 0.84) 1

Protocol and Administration

Patient Selection Criteria

Administer the FST only in patients who meet ALL of the following:

• Stage 1 or 2 AKI (not stage 3) 2, 3
• Hemodynamically stable (adequate blood pressure without escalating vasopressor requirements) 4, 5
• No severe chronic kidney disease requiring dialysis 2
• Not in volume-depleted state 4

Dosing Protocol

The standardized FST dosing is:

• 1.0 mg/kg IV furosemide for loop diuretic-naïve patients 2, 3
• 1.5 mg/kg IV furosemide for patients previously exposed to loop diuretics 2

Urine Output Monitoring

After furosemide administration:

• Measure hourly urine output for 6 hours following the test dose 3
• The first 2 hours are most predictive of outcomes 2, 3
• Calculate total urine volume in the first 2 hours post-administration 2

Interpretation of Results

Response Thresholds

A urine output of less than 200 mL in the first 2 hours post-FST predicts progression to stage 3 AKI with 73.9% sensitivity and 90.0% specificity. 2 This cutoff identifies "furosemide non-responders" who are at highest risk.

Alternative interpretation uses:

• Urine output >2 mL/kg within first 2 hours defines "furosemide responsive" status 3
• Non-responsive patients (below these thresholds) have significantly higher rates of progression to stage 3 AKI and RRT requirement 2, 3

Predictive Performance

The FST demonstrates superior performance compared to other biomarkers:

• FST outperforms plasma NGAL and proenkephalin (PENK) for predicting stage 3 AKI and KRT need 3
• Combining FST with other biomarkers does not improve diagnostic accuracy beyond FST alone 3
• FST has higher AUC (0.86) than urine TIMP-2 × IGFBP7 for predicting RRT need 1

Critical Contraindications and Warnings

Absolute Contraindications

Do NOT perform FST or use furosemide in the following situations:

• Hemodynamically unstable patients (risk of precipitating volume depletion, hypotension, and further renal hypoperfusion) 4, 5
• Patients with cirrhosis and new-onset AKI (withdraw furosemide immediately per International Club of Ascites guidelines) 4, 5
• Severe hyponatremia, worsening hepatic encephalopathy, or incapacitating muscle cramps in cirrhotic patients 5
• Within 12 hours of last fluid bolus or vasopressor administration 1

Important Safety Considerations

Furosemide increases renal oxidative stress in AKI, with the greatest increase occurring in patients with the most severe AKI who receive the highest doses. 6 This finding challenges the common practice of using high-dose furosemide to convert oliguric to non-oliguric AKI.

Additional risks include:

• Each nephrotoxic medication increases AKI odds by 53%—avoid combining furosemide with other nephrotoxins 4, 5
• Furosemide is associated with worsening renal function, with studies showing 60 mg greater daily doses in patients who deteriorated 4, 5
• Ototoxicity risk increases with aminoglycosides, cisplatin, and ethacrynic acid 7
• Severe hypotension and renal deterioration can occur when combined with ACE inhibitors or ARBs 7

Monitoring Requirements During and After FST

Immediate Monitoring (During Test)

• Hourly urine output measurement for 6 hours post-administration 3
• Continuous hemodynamic monitoring to detect hypotension 7
• Watch for signs of volume depletion: dryness of mouth, thirst, weakness, lethargy, oliguria, tachycardia 7

Laboratory Monitoring

• Electrolytes every 12-24 hours during IV diuretic therapy 4, 5
• Daily renal function assessment (serum creatinine, BUN) 4, 7
• Serum potassium, magnesium, and calcium should be monitored frequently 7
• Blood glucose monitoring in diabetic patients (furosemide may increase glucose levels) 7

Common Pitfalls and How to Avoid Them

Pitfall #1: Using FST as Treatment Rather Than Diagnostic Tool

The FST is a diagnostic test to predict outcomes, not a therapeutic intervention. 1 Level 1B evidence demonstrates that furosemide should NOT be used to prevent AKI, and Level 2C evidence states it should NOT be used to treat AKI except for volume overload management. 4, 5

Pitfall #2: Attempting to Convert Oliguric to Non-Oliguric AKI

Never use furosemide to convert oliguric to non-oliguric AKI—this practice lacks evidence of benefit and may cause harm through increased oxidative stress. 4, 5, 6

Pitfall #3: Technical Difficulties in Measurement

Up to 50% of stage 3 AKI patients may have technical difficulties with related measurements (such as renal resistive index), limiting the utility of combining FST with imaging-based assessments. 8 The FST remains valuable as a standalone functional test.

Pitfall #4: Ignoring Volume Status

The FST should only be performed after ensuring adequate intravascular volume. 1 In ARDS patients without shock, follow the FACTT-lite protocol: withhold diuretic therapy until 12 hours after the last fluid bolus or vasopressor administration. 1

Integration with Clinical Decision-Making

When FST Predicts High Risk (Non-Responsive)

For patients with urine output <200 mL in first 2 hours:

• Anticipate progression to stage 3 AKI and prepare for potential RRT 2, 3
• Intensify monitoring of renal function and fluid balance 4
• Avoid additional nephrotoxic exposures 4, 5
• Consider early nephrology consultation for RRT planning 1

When FST Predicts Low Risk (Responsive)

For patients with adequate urine response:

• Continue standard AKI management with close monitoring 2
• Reassess volume status and adjust diuretic therapy only if volume overload develops 4, 5
• Maintain nephrotoxin avoidance strategies 4

Role in RRT Discontinuation

FST can predict successful CRRT cessation with AUC of 0.84, though urine output remains a significant predictor in septic patients. 1 Consider performing FST before attempting CRRT discontinuation in non-septic patients with AKI.