Is Empagliflozin (Jardiance) effective for treating kidney stones?

Empagliflozin for Kidney Stones

Empagliflozin is effective for preventing kidney stones in non-diabetic individuals with calcium phosphate and uric acid stones, reducing relative supersaturation ratios by 36% for calcium phosphate stones and 30% for uric acid stones. 1

Mechanism of Action for Kidney Stone Prevention

Empagliflozin works through several mechanisms that may contribute to kidney stone prevention:

• Increases urine volume through osmotic diuresis
• Reduces intraglomerular pressure
• Decreases renal cortical hypoxia
• Reduces oxidative stress in the kidney
• Blunts increases in angiotensinogen
• Reduces NLRP3 inflammasome activity 2

Evidence for Kidney Stone Prevention

The most recent and highest quality evidence comes from a 2025 randomized, double-blind, placebo-controlled crossover trial specifically studying empagliflozin for kidney stone prevention:

• Study included 53 non-diabetic adults with calcium (n=28) or uric acid (n=25) kidney stones
• Participants received empagliflozin 25 mg daily or placebo for 2 weeks each
• Primary outcomes were urine relative supersaturation ratios (RSRs) for calcium oxalate, calcium phosphate, and uric acid
• Results showed:
  • In calcium stone formers: 36% reduction in calcium phosphate RSR
  • In uric acid stone formers: 30% reduction in uric acid RSR
  • No serious adverse events occurred 1

Dosing and Administration

• Standard dose: 25 mg once daily (based on kidney stone prevention trial) 1
• Can be initiated in patients with eGFR ≥20 mL/min/1.73 m² 3
• Can be continued until dialysis or transplant is needed 2

Patient Selection

Empagliflozin may be particularly beneficial for:

1. Patients with recurrent calcium phosphate stones
2. Patients with recurrent uric acid stones
3. Patients with diabetes and kidney stones (additional benefit of glycemic control)
4. Patients with chronic kidney disease and kidney stones (additional benefit of CKD progression reduction)

Monitoring and Safety Considerations

• Monitor for genital mycotic infections (6% vs 1% with placebo) 2
• Watch for signs of volume depletion, especially when combined with diuretics 2
• Consider withholding during acute illness, surgery, or critical medical illness 3
• Contraindicated in patients with eGFR <15 mL/min/1.73m² or those on dialysis 2

Additional Benefits

Beyond kidney stone prevention, empagliflozin offers:

• Slowed CKD progression (39% reduction in incident or worsening nephropathy) 3, 4
• Cardiovascular protection 3, 2
• Glycemic control in patients with diabetes 2

Clinical Application Algorithm

1. Identify patients with recurrent kidney stones (calcium phosphate or uric acid)
2. Check eGFR (must be ≥20 mL/min/1.73m²)
3. Verify absence of contraindications (eGFR <15 mL/min/1.73m², pregnancy, history of diabetic ketoacidosis)
4. Initiate empagliflozin 25 mg daily
5. Monitor:
   • Urinary supersaturation (if available)
   • Kidney stone recurrence
   • eGFR every 3-6 months
   • Signs of genital mycotic infections
   • Volume status

Conclusion

Based on the most recent high-quality evidence, empagliflozin is an effective option for preventing kidney stones in both diabetic and non-diabetic individuals, particularly for calcium phosphate and uric acid stones. The medication offers the additional benefits of kidney protection and cardiovascular risk reduction.