What is the purpose and procedure of the Lasix (furosemide) challenge test in assessing renal function, particularly in older adults with suspected acute kidney injury or chronic kidney disease?

Furosemide Stress Test in Renal Function Assessment

Purpose and Clinical Utility

The furosemide stress test (FST) is a functional assessment of tubular secretory capacity that predicts progression to severe acute kidney injury (AKI) and need for renal replacement therapy, with a urine output <200 mL in the first 2 hours after furosemide administration identifying patients at highest risk for AKI progression. 1

Primary Indications

• Risk stratification in early AKI: The FST identifies critically ill patients with early AKI who will progress to KDIGO Stage 3 AKI requiring dialysis, with an area under the ROC curve of 0.87 1
• Prediction of dialysis need: Patients producing <100 mL/hour in the first 2 hours post-FST have 87.1% sensitivity and 84.1% specificity for progression to severe AKI 1
• Assessment of tubular function: Since furosemide is actively secreted by proximal tubules, the urinary response represents residual tubular secretory capacity and functional nephron mass 2, 3
• Evaluation of interstitial fibrosis: In chronic kidney disease, lower urine output and furosemide excreted mass (FEM) correlate inversely with degree of interstitial fibrosis on biopsy (r = -0.245, p = 0.02) 4

Standardized Procedure

Dosing Protocol

• Furosemide-naive patients: Administer 1.0 mg/kg IV as a single bolus dose 1
• Patients with prior furosemide exposure: Administer 1.5 mg/kg IV as a single bolus dose 1
• Chronic dialysis patients with residual function: Consider 40 mg daily dosing to maintain urinary volume and sodium excretion 5

Measurement Protocol

• Primary endpoint: Measure total urine output at 2 hours post-administration, with <200 mL (or <100 mL/hour) indicating high risk for AKI progression 1
• Extended monitoring: Continue hourly urine output measurements for 6 hours, as progressive AKI patients demonstrate significantly lower output at each hourly interval (p<0.001) 1
• Urinary sodium measurement: Collect urine for sodium concentration to calculate total sodium excretion 4, 5
• Furosemide excreted mass: Measure urinary furosemide concentrations at 2,4, and 6 hours using established equations to determine FEM 4

Interpretation in Older Adults

Age-Related Considerations

Older adults with diabetes and hypertension have impaired renal autoregulation that increases susceptibility to ischemic tubular injury, making FST interpretation particularly valuable in this population. 6

• Baseline renal function: Use mean outpatient creatinine from 7-365 days before admission as true baseline, as admission creatinine underestimates community-acquired AKI 7
• Sarcopenia effects: Consider cystatin C measurement in older adults, as low muscle mass may underestimate kidney dysfunction when using creatinine alone 7

Response Patterns

• Good responders (>200 mL in 2 hours): Retain significant tubular function and are less likely to progress to dialysis-requiring AKI 1
• Poor responders (<200 mL in 2 hours): Have severe tubular dysfunction and 87.1% likelihood of progressing to KDIGO Stage 3 AKI 1
• Chronic kidney disease: Progressive decline in total urine output and FEM correlates with advancing interstitial fibrosis grades (p = 0.015 for grade 3 fibrosis) 4

Critical Management Implications

When FST Predicts Progression

Immediately discontinue all nephrotoxic medications including NSAIDs, aminoglycosides, ACE inhibitors, ARBs, and contrast agents when FST indicates high progression risk. 8, 7, 6

• Volume management: Assess volume status through jugular venous pressure, peripheral edema, and lung auscultation; provide isotonic crystalloid resuscitation only if hypovolemic 7
• Medication adjustment: Adjust all drug dosages based on current reduced GFR, as kidney function changes dynamically during AKI 7
• Diuretic withdrawal: Stop diuretics after ATN diagnosis is confirmed, as continuing furosemide during AKI causes ongoing kidney damage and increases mortality 8, 7
• RRT preparation: Monitor for dialysis indications including severe/refractory hyperkalemia, metabolic acidosis, volume overload unresponsive to diuretics, and uremic symptoms 8, 6

Pharmacologic Basis

The severity of AKI significantly affects diuretic response to furosemide because it must be actively secreted by proximal tubules into urine before reaching its site of action at the ascending limb of Henle—urinary concentrations, not serum levels, determine diuretic effect. 3

• Tubular secretion: Furosemide requires functional proximal tubular secretory mechanisms; impaired secretion in AKI reduces urinary drug delivery 2, 3
• Dose-response relationship: Higher doses may be needed in AKI to achieve therapeutic urinary concentrations, but poor response indicates severe tubular dysfunction rather than inadequate dosing 3

Common Pitfalls to Avoid

• Misinterpreting poor response as indication for higher doses: A poor FST response indicates severe tubular injury requiring RRT consideration, not need for escalating diuretic doses 1
• Continuing diuretics after positive FST: Ongoing loop diuretic use in established ATN increases mortality and should be discontinued 8, 7
• Ignoring volume status: FST should not replace clinical volume assessment; hypovolemic patients require fluid resuscitation regardless of FST results 7
• Using FST as therapeutic intervention: The test is diagnostic/prognostic, not therapeutic—current evidence does not suggest furosemide reduces mortality in AKI 3
• Delaying RRT based on preserved urine output: While good FST response predicts lower progression risk, clear RRT indications (severe hyperkalemia, refractory acidosis, uremic symptoms) mandate dialysis initiation regardless of urine output 8, 6

Follow-Up Requirements

• Short-term monitoring: Evaluate renal function within 3-7 days after FST and any clinical status change 7
• Three-month assessment: Perform follow-up at 3 months post-AKI to assess for resolution versus progression to chronic kidney disease 8, 7
• Long-term surveillance: Even with complete creatinine recovery, patients face significantly increased risks of recurrent AKI, CKD progression, and cardiovascular events requiring nephrology co-management 6