Why should a sodium‑glucose co‑transporter‑2 (SGLT‑2) inhibitor be discontinued when a patient initiates chronic dialysis?

Why Discontinue SGLT2 Inhibitors in Dialysis

SGLT2 inhibitors should be discontinued when patients initiate chronic dialysis because they have not been adequately studied in this population, lack proven efficacy once kidney replacement therapy begins, and guideline recommendations explicitly state to stop them at dialysis initiation. 1

Guideline-Based Rationale for Discontinuation

The most recent KDIGO 2022 guidelines provide clear direction on this issue:

• Once kidney replacement therapy is initiated, SGLT2 inhibitors should be discontinued 1
• The 2020 KDIGO guidelines similarly state that SGLT2 inhibitors can be continued even if eGFR falls below 30 ml/min per 1.73 m², "unless it is not tolerated or kidney replacement therapy is initiated" 1
• This recommendation applies to both hemodialysis and peritoneal dialysis 1, 2

Mechanistic Loss of Benefit

The primary mechanisms by which SGLT2 inhibitors provide kidney and cardiovascular protection become irrelevant once dialysis begins:

• SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule, triggering tubuloglomerular feedback that reduces intraglomerular pressure 3, 4
• In dialysis patients with minimal or no residual kidney function, there is insufficient tubular function for the drug to exert its protective hemodynamic effects 3
• The glucose-lowering effect becomes negligible without functioning nephrons to excrete glucose 3

Safety Concerns in Dialysis

While limited data exists, potential risks outweigh uncertain benefits:

• Risk of euglycemic ketoacidosis remains present even without significant glucose-lowering effect, particularly during acute illness 2, 3
• One small observational study in peritoneal dialysis patients showed SGLT2 inhibitors were associated with subclinical metabolic acidosis (lower venous CO2) 5
• Volume depletion risk persists, which is particularly problematic in dialysis patients requiring careful fluid management 2

Lack of Evidence in ESKD Population

All major SGLT2 inhibitor cardiovascular and kidney outcome trials excluded patients with end-stage kidney disease 6:

• The CREDENCE trial, which established kidney benefits, only enrolled patients with eGFR 30 to <90 ml/min per 1.73 m² 3
• No randomized controlled trial data exists demonstrating benefit in dialysis patients 6
• Current use in dialysis would be entirely off-label without evidence of efficacy 6

Emerging Research vs. Current Practice

While some researchers are exploring potential cardiovascular benefits in dialysis patients through direct cardiac effects (reduced intracellular sodium/calcium, decreased inflammation, improved autophagy) 6, this remains investigational:

• One retrospective study of 11 peritoneal dialysis patients continuing SGLT2 inhibitors showed increased ultrafiltration and hemoglobin but also lower CO2 levels 5
• These preliminary findings do not override guideline recommendations to discontinue at dialysis initiation 1, 2
• Ongoing clinical trials may eventually provide evidence, but current standard of care is discontinuation 6

Common Pitfall to Avoid

Do not confuse the recommendation to continue SGLT2 inhibitors as eGFR declines below 20 ml/min per 1.73 m² with permission to continue on dialysis 1:

• The guideline explicitly distinguishes between progressive CKD (where continuation is reasonable) and initiation of kidney replacement therapy (where discontinuation is indicated) 1, 2
• The kidney and cardiovascular protective effects demonstrated in trials apply to patients with functioning kidneys, not those on dialysis 3, 6