Is canagliflozin (SGLT2 inhibitor) safe to use in a patient with Chronic Kidney Disease (CKD) and impaired renal function, specifically a Creatinine Clearance (CrCl) of 18?

Canagliflozin Use in an 87-Year-Old with CKD and CrCl 18

Canagliflozin is not recommended for patients with a creatinine clearance of 18 mL/min due to reduced efficacy and potential safety concerns in advanced kidney disease. 1

Recommendations Based on Renal Function

• Canagliflozin is not recommended for glucose lowering in patients with eGFR <30 mL/min/1.73m² 1
• The patient's CrCl of 18 mL/min is well below the threshold for safe use of canagliflozin 1
• Current guidelines specifically contraindicate SGLT2 inhibitors in patients on dialysis, and this patient's renal function is approaching dialysis levels 1

Evidence from Clinical Trials

• The CREDENCE trial, which demonstrated renal benefits of canagliflozin, only included patients with eGFR ≥30 mL/min/1.73m² 2, 3
• Efficacy of SGLT2 inhibitors is significantly blunted at very low eGFR levels, limiting potential benefits 1
• The 2022 KDIGO guidelines recommend SGLT2 inhibitors only for patients with eGFR ≥20 mL/min/1.73m², and this patient's CrCl of 18 falls below this threshold 1

Safety Concerns in Advanced CKD

• At very low GFR levels (CrCl 18), there is increased risk of:
  • Volume depletion and hypotension, particularly concerning in an elderly patient 1, 4
  • Acute kidney injury 1
  • Limited glycemic efficacy due to reduced renal filtration of glucose 5
  • Electrolyte abnormalities 1

Age Considerations

• At 87 years old, this patient is at higher risk for adverse effects from volume depletion 4
• Elderly patients with advanced CKD have reduced physiologic reserve to compensate for potential adverse effects 4
• The risk-benefit ratio becomes unfavorable at this level of renal impairment in an elderly patient 1, 4

Alternative Approaches

• For patients with this degree of renal impairment (CrCl 18), consider:
  • GLP-1 receptor agonists that don't require dose adjustment for renal function 1
  • DPP-4 inhibitors with appropriate dose adjustments 1
  • Insulin with careful dose titration 1

Monitoring if Medication is Continued Despite Recommendations

• If clinical decision is made to use canagliflozin despite recommendations against it:
  • Monitor renal function more frequently (every 2-4 weeks initially) 1
  • Assess for volume depletion symptoms 1
  • Consider reducing or discontinuing concurrent diuretics 1
  • Implement a "sick day protocol" to temporarily withhold medication during illness 1
  • Monitor for urinary tract and genital mycotic infections 4, 5

Summary of Guideline Recommendations

• 2022 KDIGO guidelines set the lower limit for SGLT2 inhibitor initiation at eGFR ≥20 mL/min/1.73m² 1
• Mayo Clinic guidance specifically states canagliflozin is "not recommended for glucose lowering in T2D patients with eGFR <30" 1
• ESC guidelines recommend SGLT2 inhibitors only if eGFR is 30 to <90 mL/min/1.73m² 1