Dapagliflozin Use in Patients with Kidney Stones
Dapagliflozin (Forxiga) is generally not recommended as a first-line treatment for patients with kidney stones due to its mechanism of action that increases urinary glucose excretion, which could potentially exacerbate stone formation.
Mechanism of Action and Kidney Stone Considerations
Dapagliflozin is an SGLT2 inhibitor that works by preventing glucose reabsorption in the proximal tubule, leading to increased urinary glucose excretion. This mechanism raises several concerns for patients with kidney stones:
- Increased urinary glucose can alter urinary composition and potentially contribute to stone formation
- The drug's diuretic effect may cause volume depletion, which can concentrate urine and increase stone risk
- Changes in urinary pH from SGLT2 inhibition might affect stone crystallization
Guideline Recommendations for Dapagliflozin Use
Dapagliflozin is primarily indicated for:
- Glucose lowering in type 2 diabetes with eGFR ≥45 mL/min/1.73m² 1
- Risk reduction of sustained eGFR decline, kidney failure, CV death, and hospitalization for heart failure in adults with CKD 1
- Risk reduction of hospitalization for heart failure in adults with type 2 diabetes and established CVD or multiple CV risk factors 1
Dosing and Renal Function Considerations:
- For patients with eGFR ≥45 mL/min/1.73m²: 10 mg once daily 1
- For patients with eGFR 25 to <45 mL/min/1.73m²: 10 mg once daily (for HF or CKD indications) 1
- For patients with eGFR <25 mL/min/1.73m²: initiation not recommended, but may continue 10 mg in patients with HF and CKD 1
- Contraindicated in dialysis 1
Benefits vs. Risks in Patients with Kidney Stones
Potential Benefits:
- Dapagliflozin has demonstrated significant renoprotective effects in the DAPA-CKD trial with a 39% reduction in the primary composite outcome 2
- Slows eGFR decline by 0.95 mL/min per 1.73 m² per year compared to placebo 3
- Benefits observed even in advanced CKD (Stage 4) with a 27% reduction in the primary composite endpoint 4
Potential Risks for Stone Formers:
- Volume depletion from the diuretic effect may concentrate urine and increase stone risk 5
- Increased urinary glucose excretion could alter urinary composition
- Risk of urinary tract infections, which can complicate kidney stone management
Clinical Decision Algorithm for Dapagliflozin in Patients with Kidney Stones
Assess stone risk factors and composition:
- Uric acid stones: Higher risk with dapagliflozin due to potential urinary acidification
- Calcium oxalate stones: Potential risk due to volume depletion
- Struvite stones: No clear additional risk
Consider renal function:
- eGFR ≥45 mL/min/1.73m²: Standard dosing (10 mg daily) if benefits outweigh risks
- eGFR 25-45 mL/min/1.73m²: Use only for HF or CKD indications, not for glycemic control
- eGFR <25 mL/min/1.73m²: Do not initiate
Evaluate hydration status and risk of volume depletion:
- High risk patients (elderly, on diuretics): Consider alternative agents
- Counsel on increased fluid intake if dapagliflozin is used
Alternative SGLT2 inhibitors:
Monitoring Recommendations if Dapagliflozin is Used
- Increase fluid intake to at least 2-3 liters per day
- Monitor for signs of volume depletion (orthostatic hypotension, dizziness)
- Regular urinalysis to check for hematuria and crystalluria
- Periodic imaging to assess stone burden in patients with recurrent stones
- Monitor renal function regularly, especially during intercurrent illness
Conclusion
For patients with kidney stones, dapagliflozin should be used with caution due to its mechanism of action that could potentially exacerbate stone formation. If cardiorenal protection is needed, consider alternative SGLT2 inhibitors or other medication classes with less potential impact on stone formation. When dapagliflozin must be used in patients with kidney stones, implement aggressive hydration strategies and close monitoring.