Should I stop the sodium‑glucose co‑transporter‑2 inhibitor (e.g., empagliflozin, canagliflozin, dapagliflozin) in a patient who has kidney stones?

SGLT2 Inhibitors and Kidney Stones: No Need to Discontinue

You do not need to stop SGLT2 inhibitors in patients with kidney stones. In fact, emerging evidence suggests these medications may actually reduce kidney stone recurrence risk by lowering urinary supersaturation of stone-forming compounds.

Evidence Supporting Continuation

Kidney Stone Prevention Benefits

Recent high-quality trial data demonstrates that empagliflozin substantially reduces the risk factors for stone formation in non-diabetic kidney stone formers 1:

• For calcium stone formers: Empagliflozin reduced calcium phosphate supersaturation by 36% (95% CI: -48% to -21%, P < 0.001) 1
• For uric acid stone formers: Empagliflozin reduced uric acid supersaturation by 30% (95% CI: -44% to -12%, P = 0.002) 1
• These reductions in urinary supersaturation are validated surrogates for stone recurrence prevention 1
• No serious adverse events occurred in stone formers treated with empagliflozin 1

Guideline Support for Continuation

The KDIGO 2022 guidelines provide clear direction on when to continue versus withhold SGLT2 inhibitors, and kidney stones are not listed as an indication for discontinuation 2:

Continue SGLT2 inhibitors in patients with:

• Stable chronic kidney disease, even when eGFR falls below 20 mL/min/1.73 m² 2
• Reversible eGFR decreases after initiation (expected and not harmful) 2, 3
• History of kidney stones (no contraindication mentioned in guidelines) 2

Temporarily withhold SGLT2 inhibitors only during:

• Prolonged fasting or critical medical illness (ketosis risk) 2, 3, 4
• Surgery requiring ≥2 days hospitalization or bowel preparation 2, 4
• Acute illness with significant fluid losses or volume depletion 3, 4
• Active acute kidney injury from other causes 3

Clinical Reasoning

Why SGLT2 Inhibitors May Help Stone Formers

The mechanism by which SGLT2 inhibitors reduce stone risk involves:

• Mild osmotic diuresis increasing urine volume 5
• Reduced urinary supersaturation of calcium phosphate and uric acid 1
• Modest increases in urine output without significant electrolyte disturbances 5, 6

Cardiovascular and Renal Protection Outweighs Theoretical Concerns

The proven benefits of SGLT2 inhibitors for kidney and cardiovascular protection far exceed any theoretical stone-related concerns 2, 7:

• Strong recommendation (1A) for use in patients with CKD and eGFR ≥20 mL/min/1.73 m² 2
• Reduction in cardiovascular death, heart failure hospitalization, and CKD progression 2, 7
• Benefits extend to both diabetic and non-diabetic CKD patients 2, 7

Common Pitfalls to Avoid

Do not confuse kidney stones with contraindications to SGLT2 inhibitors. The actual contraindications and situations requiring temporary discontinuation are 2, 3, 4:

• Active ketoacidosis or high ketosis risk during acute illness 4, 8
• Severe volume depletion or hemodynamic instability 2, 3
• Perioperative period for major surgery 2, 4
• Initiation of kidney replacement therapy 2

Do not stop SGLT2 inhibitors for an acute stone episode unless:

• The patient requires surgery with prolonged fasting (withhold ≥2 days before procedure) 2, 4
• Severe volume depletion develops from vomiting/poor oral intake (temporarily withhold until stable) 3, 4
• The patient develops concurrent AKI from obstruction or other causes (withhold until resolution) 3

Practical Management Algorithm

For patients with history of kidney stones on SGLT2 inhibitors:

1. Continue the SGLT2 inhibitor for its proven cardiovascular and renal benefits 2, 1
2. Optimize stone prevention measures (adequate hydration, dietary modifications) 1
3. Monitor for volume status if concurrent diuretic use 2
4. Educate on sick-day rules to temporarily withhold during acute illness with poor oral intake 2, 3, 4

For acute stone episodes:

• Continue SGLT2 inhibitor if patient maintains oral intake and normal volume status 2, 3
• Temporarily withhold only if surgery planned, severe vomiting, or AKI develops 3, 4
• Resume once eating/drinking normally and acute illness resolved 3, 4

The presence of kidney stones is not a reason to avoid or discontinue SGLT2 inhibitors, and these agents may actually provide stone prevention benefits while delivering critical cardiovascular and renal protection 2, 1.