When to start a Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitor, such as canagliflozin (canagliflozin), on a patient with Chronic Kidney Disease (CKD) stage 3b?

SGLT2 Inhibitors in CKD Stage 3b: Initiation Guidelines

SGLT2 inhibitors should be initiated in all patients with CKD stage 3b (eGFR 30-44 mL/min/1.73 m²) who have an eGFR ≥20 mL/min/1.73 m², regardless of diabetes status. 1

Patient Selection and Initiation Criteria

For Patients with Type 2 Diabetes:

• Start SGLT2 inhibitor immediately in all patients with T2DM and CKD stage 3b with eGFR ≥20 mL/min/1.73 m² (strong recommendation, 1A evidence) 1
• No need to wait for glycemic control failure with other agents
• Benefits extend beyond glycemic control to include kidney protection and cardiovascular risk reduction

For Patients without Diabetes:

• Start SGLT2 inhibitor in patients with:
  • eGFR ≥20 mL/min/1.73 m² with urine ACR ≥200 mg/g (≥20 mg/mmol) (strong recommendation, 1A evidence) 1
  • Heart failure, irrespective of albuminuria level (strong recommendation, 1A evidence) 1
  • Consider in those with urine ACR <200 mg/g (<20 mg/mmol) (weaker recommendation, 2B evidence) 1

Medication Selection in CKD Stage 3b

Preferred Agents:

• Canagliflozin: Maximum 100 mg daily in stage 3b 1
• Dapagliflozin: 10 mg daily in stage 3b 1

Not Recommended in Stage 3b:

• Empagliflozin: Not recommended with eGFR <45 mL/min/1.73 m² 1, 2
• Ertugliflozin: Not recommended with eGFR <45 mL/min/1.73 m² 1, 2

Monitoring and Follow-up

1. Initial Monitoring:

   • Check serum creatinine, potassium, and blood pressure within 2-4 weeks of initiation 1
   • Expect a small, reversible decrease in eGFR (typically <0.2 mg/dL) within first 6 weeks 3
   • This initial eGFR decline is hemodynamic and not a reason to discontinue therapy 1

2. Ongoing Monitoring:

   • Regular monitoring of kidney function
   • Watch for volume depletion, especially in elderly or those on diuretics
   • Monitor for genital mycotic infections (more common in women) 1

Special Considerations

Safety Precautions:

• Temporarily withhold during:
  • Prolonged fasting
  • Surgery
  • Critical illness
  • Acute illness that may increase risk of ketoacidosis 1

Continuation Protocol:

• Once initiated, continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² unless:
  • Not tolerated
  • Kidney replacement therapy is initiated 1

Combination Therapy:

• Can be used alongside RAS inhibitors (ACEi/ARB)
• Consider adding nonsteroidal MRA (e.g., finerenone) in patients with T2DM, eGFR >25 mL/min/1.73 m², normal potassium, and persistent albuminuria despite RASi 1

Common Pitfalls to Avoid

1. Inappropriate discontinuation due to initial eGFR decline (this is expected and usually stabilizes) 1

2. Failure to initiate in eligible patients due to concerns about reduced efficacy in CKD (benefits for kidney and cardiovascular outcomes persist even with reduced glycemic effects) 4, 5

3. Overlooking non-glycemic benefits - SGLT2 inhibitors in CKD stage 3b provide:

   • Reduction in CKD progression
   • Decreased risk of heart failure hospitalization
   • Reduced cardiovascular mortality
   • Weight loss and blood pressure reduction 6, 7

4. Inadequate patient education about:

   • Genital mycotic infection risk (occurs in ~6% of patients) 1
   • Risk of euglycemic ketoacidosis, especially in insulin users 1
   • Volume depletion symptoms

SGLT2 inhibitors represent a paradigm shift in CKD management, offering kidney protection independent of glycemic control. The evidence strongly supports their use in CKD stage 3b, with benefits outweighing risks in properly selected patients.