In a 68-year-old woman taking torsemide (loop diuretic), dapagliflozin (Farxiga), gabapentin, and allopurinol, with normal creatinine and estimated glomerular filtration rate but a BUN/creatinine ratio of 41, how should I manage her?

Management of Elevated BUN/Creatinine Ratio in a Patient on Torsemide and Dapagliflozin

This patient has prerenal azotemia from volume depletion caused by the combination of torsemide and dapagliflozin, and you should temporarily reduce or hold the torsemide while continuing dapagliflozin, then reassess volume status and renal function within 48-72 hours. 1, 2

Understanding the Clinical Picture

The BUN/creatinine ratio of 41 (normal is approximately 10-20:1) strongly indicates prerenal azotemia from hypovolemia rather than intrinsic renal disease, since the creatinine and GFR remain normal. 2 This pattern occurs when:

• Loop diuretics like torsemide cause significant urinary sodium and water losses, leading to volume contraction and reduced renal perfusion 1, 3
• Dapagliflozin adds osmotic diuresis by promoting renal glucose excretion, which compounds the volume depletion 4, 5
• The kidneys respond to decreased perfusion by increasing BUN reabsorption disproportionately to creatinine, creating the elevated ratio 1

This is not acute kidney injury because the creatinine and GFR are normal—it represents functional volume depletion that will reverse with appropriate fluid management. 1, 2

Immediate Management Algorithm

Step 1: Adjust Diuretic Therapy (Within 24 Hours)

Reduce torsemide by 50% or hold it temporarily until volume status normalizes and the BUN/creatinine ratio improves. 1, 2 The guideline explicitly states that when BUN rises disproportionately to creatinine, this is "usually corrected by reducing the diuretic dose and is not necessarily an indication to reduce or stop the ACE inhibitor." 1

• If the patient has no signs of volume overload (no edema, dyspnea, or orthopnea), hold torsemide completely 2
• If mild volume overload persists, reduce torsemide to 50% of the current dose 2
• Continue dapagliflozin because its cardiovascular and renal benefits outweigh the transient volume effects, and stopping it would eliminate proven mortality reduction 1, 6

Step 2: Assess Volume Status Clinically

Examine for signs that guide your next steps:

• Hypovolemia indicators: orthostatic hypotension, decreased skin turgor, dry mucous membranes, tachycardia 2
• Euvolemia indicators: normal jugular venous pressure, no peripheral edema, stable weight 2
• Volume overload indicators: elevated JVP, peripheral edema, pulmonary crackles, weight gain >2 kg over 3 days 1, 2

If hypovolemia is confirmed, initiate isotonic saline (0.9% NaCl) to restore extracellular fluid volume. 2 If euvolemic or mildly hypervolemic, simply reduce the diuretic without adding IV fluids. 2

Step 3: Monitor Laboratory Parameters

Recheck BUN, creatinine, and electrolytes within 48-72 hours after adjusting diuretics. 3, 2 You should see:

• BUN/creatinine ratio normalize toward 10-20:1 2
• Stable or improved creatinine and GFR 1, 5
• Correction of any electrolyte abnormalities (particularly potassium and sodium) 1, 3

Track daily weights and urine output to objectively assess response to therapy. 2

Why Continue Dapagliflozin Despite Volume Depletion

Dapagliflozin provides critical cardiovascular and renal protection that should not be interrupted for transient volume issues. The evidence is compelling:

• In the DAPA-CKD trial, dapagliflozin reduced the risk of kidney failure, cardiovascular death, and all-cause mortality by 31-39% in patients with chronic kidney disease 6
• The initial small decline in eGFR with dapagliflozin (typically 3-5 mL/min) is hemodynamic and reversible, representing reduced intraglomerular pressure rather than kidney damage 5, 6
• This transient eGFR dip is followed by long-term preservation of kidney function, with slower rates of eGFR decline compared to placebo 5, 6
• The 2022 ADA/KDIGO consensus explicitly states: "Once initiated, the SGLT2i can be continued at lower levels of eGFR" 1

Dapagliflozin's safety profile in this scenario is well-established: mean eGFR showed small transient reductions at week 1 but returned to near baseline by week 24 and remained stable through 102 weeks. 5

Long-Term Diuretic Strategy After Stabilization

Once the BUN/creatinine ratio normalizes and volume status is optimized:

Option 1: Restart Torsemide at Lower Dose (Preferred for Heart Failure)

• Resume torsemide at 50% of the original dose if ongoing diuresis is needed 2
• Torsemide has mild anti-aldosterone activity that causes relatively less potassium wasting compared to furosemide 3
• Monitor potassium, BUN, and creatinine within 3-7 days, then monthly for 3 months, then every 3-6 months 3

Option 2: Add Potassium-Sparing Diuretic (If Hypokalemia Develops)

If the patient develops hypokalemia (K+ <4.0 mEq/L) on torsemide:

• Add spironolactone 25-50 mg daily rather than chronic oral potassium supplements 3
• Spironolactone provides more stable potassium levels and confers mortality benefit in heart failure 3
• Check potassium and creatinine every 5-7 days until stable, then follow the standard monitoring schedule 3

Option 3: Switch to Thiazide (Only If No CKD and Hypertension Predominates)

Thiazides are ineffective when GFR <30-40 mL/min and may further reduce GFR, so they should be avoided if the patient has any degree of renal impairment. 1, 7 Given this patient's normal GFR, a thiazide could be considered if hypertension is the primary indication, but loop diuretics remain preferred for volume management. 1

Medication-Specific Considerations

Gabapentin

• Requires dose adjustment if GFR declines below 60 mL/min, but at normal GFR no adjustment is needed 7
• Monitor for accumulation if renal function worsens 7

Allopurinol

• No dose adjustment needed at normal GFR 7
• If GFR falls below 60 mL/min, reduce dose to prevent toxicity 7

Dapagliflozin

• Continue at 10 mg daily as long as eGFR remains ≥25 mL/min 1
• The 2022 ADA/KDIGO guideline states: "Initiation not recommended with eGFR <25 mL/min/1.73 m²; may continue if tolerated for kidney and CV benefit until dialysis" 1
• Glucose-lowering efficacy decreases as eGFR declines, but cardiovascular and kidney benefits persist 1

Critical Pitfalls to Avoid

Do not stop dapagliflozin based solely on an elevated BUN/creatinine ratio with normal creatinine—this represents functional prerenal azotemia, not acute kidney injury, and stopping dapagliflozin eliminates proven mortality benefit. 1, 6

Do not add hypertonic saline if the patient has any signs of volume overload, as this worsens fluid retention. 2

Do not continue the full-dose torsemide while evaluating the patient—immediate dose reduction takes priority over prolonged diagnostic workup when prerenal azotemia is evident. 1, 2

Do not assume this patient needs aggressive IV hydration without first confirming hypovolemia clinically—many patients with elevated BUN/creatinine ratios are actually euvolemic and simply need diuretic dose reduction. 2

Avoid NSAIDs entirely as they cause sodium retention, worsen renal function, and dramatically increase hyperkalemia risk when combined with dapagliflozin and diuretics. 1, 3

Monitoring Schedule Going Forward

• Week 1: Recheck BUN, creatinine, electrolytes, and eGFR after diuretic adjustment 3, 2
• Weeks 2-4: Continue weekly monitoring until BUN/creatinine ratio normalizes 3
• Month 1-3: Monthly monitoring of renal function and electrolytes 3
• Beyond 3 months: Every 3-6 months if stable 3

Implement sodium restriction to ≤2 g/day (≤90 mmol/day) to reduce diuretic requirements and minimize electrolyte disturbances. 1, 7