Is dapagliflozin (SGLT2 inhibitor) effective for preventing kidney stone recurrence?

Dapagliflozin for Kidney Stone Prevention

Dapagliflozin is not currently recommended for the prevention of kidney stone recurrence as there is insufficient evidence supporting its efficacy for this specific indication.

Current Evidence for Kidney Stone Prevention

The American College of Physicians (ACP) clinical practice guidelines for preventing recurrent nephrolithiasis recommend specific interventions that have demonstrated efficacy:

1. First-line approach: Increased fluid intake spread throughout the day to achieve at least 2 L of urine per day 1
2. Pharmacologic options when increased fluid intake fails:
   • Thiazide diuretics
   • Citrate supplements
   • Allopurinol (particularly for calcium stones with hyperuricosuria) 1

SGLT2 Inhibitors and Kidney Stones: Emerging Research

While SGLT2 inhibitors like dapagliflozin have well-established benefits for chronic kidney disease and cardiovascular outcomes, their role in kidney stone prevention remains investigational:

• The SWEETSTONE trial is currently investigating empagliflozin's effects on urinary supersaturations in non-diabetic kidney stone formers, but results are not yet available 2
• Explanatory analyses of SGLT2 inhibitor trials have suggested a 30-50% reduced rate of stone events in patients with diabetes, but the mechanisms remain unclear 2

Established Indications for Dapagliflozin

Dapagliflozin has strong evidence supporting its use for:

1. Chronic kidney disease: Recommended for patients with eGFR ≥20 mL/min/1.73 m² and urine albumin-to-creatinine ratio ≥200 mg/g or heart failure 1
2. Type 2 diabetes with CKD: First-line standard of care for kidney and heart protection 1
3. Heart failure: Particularly beneficial for heart failure with reduced ejection fraction 1

Potential Mechanisms Relevant to Kidney Stones

While not proven for kidney stone prevention, dapagliflozin's mechanisms might theoretically affect stone formation through:

• Increased urinary volume due to osmotic diuresis
• Changes in urinary pH and electrolyte composition
• Reduced uric acid levels

Clinical Approach to Kidney Stone Prevention

For patients with recurrent kidney stones:

1. First-line approach: Increase fluid intake to achieve >2L urine output daily

2. Dietary modifications based on stone composition:

   • Maintain normal dietary calcium
   • Reduce sodium and animal protein intake
   • Limit dietary oxalate for calcium oxalate stones

3. Pharmacologic therapy when increased fluid intake fails:

   • For calcium stones: Thiazide diuretics or citrate supplements
   • For uric acid stones: Allopurinol and urinary alkalinization
   • For cystine stones: Thiol-containing medications

Safety Considerations with SGLT2 Inhibitors

If considering dapagliflozin for its established indications in patients with kidney stones:

• Monitor for genital mycotic infections (more common in women)
• Implement sick day protocols during acute illness
• Watch for volume depletion, especially if combined with diuretics
• Be alert for euglycemic ketoacidosis in patients with diabetes 1

Conclusion

While dapagliflozin has proven benefits for CKD and cardiovascular outcomes, current guidelines do not support its use specifically for kidney stone prevention. Patients with recurrent kidney stones should be managed with established preventive strategies including increased fluid intake and, when necessary, appropriate pharmacologic therapy based on stone composition.