In a patient with chronic kidney disease and bilateral pedal edema who was started on a torsemide infusion, has good urine output and reduced edema, but serum creatinine increased from 2 mg/dL to 3 mg/dL, what is the most likely cause?

Creatinine Rise During Torsemide Diuresis in CKD

Most Likely Cause

The creatinine increase from 2 to 3 mg/dL during torsemide infusion with good urine output and improving edema most likely represents overly aggressive diuresis causing intravascular volume depletion and reduced renal perfusion (pre-renal azotemia), rather than true tubular injury. 1

Understanding the Clinical Context

This scenario presents a common dilemma in managing fluid overload in CKD patients:

• Torsemide is primarily hepatically eliminated (80% hepatic metabolism, 20% renal excretion), making it particularly suitable for CKD patients as it does not accumulate with reduced kidney function 2, 3
• The patient demonstrates clinical improvement (reduced pedal edema, good urine output), yet creatinine worsened—this dissociation suggests a hemodynamic rather than structural kidney problem 1
• In CKD patients with fluid overload, serum creatinine may be artificially diluted by volume expansion, and as decongestion occurs, creatinine can rise without representing true tubular injury 1

Mechanism of Creatinine Rise

Pre-renal Azotemia from Overzealous Diuresis

• Loop diuretics cause the greatest effect with initial doses, leading to significant fluid and electrolyte shifts within the first 3 days 4
• With reduced kidney perfusion from excessive volume removal, there is decreased GFR despite patent tubules 4
• Patients with CKD and symptomatic fluid overload face the highest initial risk of renal deterioration, which is further increased by their need for higher diuretic doses 4

Distinguishing Hemodynamic Change from True Injury

• A creatinine rise during active diuresis without evidence of tubular injury (muddy brown casts, positive NGAL/KIM-1) represents hemodynamic adjustment rather than kidney damage 1, 5
• Urinalysis with microscopy is crucial—absence of significant findings (no casts, no proteinuria) supports pre-renal etiology 1
• The American Heart Association recommends continuing aggressive decongestion while monitoring creatinine serially, as small creatinine increases during decongestion without tubular injury should not halt diuresis 1

Immediate Assessment Steps

Volume Status Evaluation

• Assess for signs of intravascular volume depletion: orthostatic hypotension, tachycardia, decreased skin turgor, dry mucous membranes 1
• Check jugular venous pressure—if flat or low, this confirms excessive volume removal 1
• Calculate fractional excretion of sodium (FENa) <1% which would confirm pre-renal azotemia 1

Laboratory Workup

• Obtain urinalysis with microscopy immediately to rule out acute tubular necrosis (look for muddy brown casts) 1
• Check BUN:creatinine ratio—ratio >20:1 suggests pre-renal azotemia 1
• Measure serum electrolytes, particularly sodium, potassium, and chloride 4
• Hypochloremia and metabolic alkalosis both antagonize loop diuretic effects and trigger compensatory neurohormonal responses 4

Management Algorithm

If Pre-renal Azotemia Confirmed (FENa <1%, BUN:Cr >20:1, no casts on urinalysis):

1. Temporarily reduce or hold torsemide infusion 1
2. Provide cautious volume repletion with isotonic saline (250-500 mL bolus) and reassess 1
3. Monitor urine output, vital signs, and repeat creatinine in 24-48 hours 1
4. Once creatinine stabilizes or improves, resume diuresis at lower rate 1

If Intrinsic Renal Injury Suspected (muddy brown casts, FENa >2%):

1. Discontinue torsemide temporarily 1
2. Evaluate for nephrotoxic medications or other AKI triggers 1
3. Consider nephrology consultation 1

Monitoring Strategy During Diuresis

• The American Journal of Kidney Diseases recommends measuring creatinine every 48 hours during active diuresis 1
• Monitor for true AKI development (≥0.3 mg/dL increase within 48 hours from most recent baseline) 4, 1
• Serial measurements are essential because the greatest diuretic effect and electrolyte shifts occur within the first 3 days 4
• Check serum potassium frequently—patients with CKD have approximately five times higher risk of hyperkalemia during diuresis 6

Common Pitfalls to Avoid

• Don't stop diuresis prematurely based solely on creatinine rise without assessing volume status and urinalysis 1
• Don't assume all creatinine increases represent kidney injury—hemodynamic changes during decongestion are expected and acceptable 1, 5
• Don't ignore electrolyte abnormalities, particularly hypochloremia and hypokalemia, which can worsen diuretic resistance and trigger compensatory sodium retention 4
• Avoid NSAIDs, which can convert hemodynamic creatinine changes into true AKI 6
• Always assess volume status first when creatinine rises during diuresis, as volume depletion can convert a manageable hemodynamic effect into problematic acute kidney injury 5

Diuretic Resistance Considerations

• CKD itself contributes to diuretic resistance through accumulation of organic anions that compete for diuretic secretion in the proximal tubule and diminished filtered sodium load 4
• Nephron remodeling with distal tubular hypertrophy increases distal sodium reabsorption, requiring higher diuretic doses over time 4
• If diuretic resistance develops, consider sequential nephron blockade with addition of thiazide-type diuretic or acetazolamide 4
• The CLOROTIC trial showed that adding hydrochlorothiazide to loop diuretics achieved greater decongestion at the expense of higher rates of creatinine elevation, though clinical outcomes remained neutral 4