Can Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors be initiated in patients with Chronic Kidney Disease (CKD) stage 4?

SGLT2 Inhibitors in CKD Stage 4: Recommendations for Initiation

SGLT2 inhibitors can be initiated in patients with CKD stage 4 (eGFR 15-29 mL/min/1.73 m²) who have an eGFR ≥20 mL/min/1.73 m², with proven kidney and cardiovascular benefits. 1

Evidence-Based Recommendations for SGLT2 Initiation in CKD 4

eGFR Thresholds

• SGLT2 inhibitors can be initiated when eGFR ≥20 mL/min/1.73 m²
• Do not initiate when eGFR <20 mL/min/1.73 m²
• Once initiated, SGLT2 inhibitors can be continued even if eGFR falls below initiation thresholds, until dialysis is required 1

Agent-Specific Considerations

• Dapagliflozin: Can be initiated with eGFR ≥25 mL/min/1.73 m² 1
• Canagliflozin: Initiation not recommended in CKD 4, but may continue 100 mg daily if previously started 1
• Empagliflozin: Use not recommended with eGFR <45 mL/min/1.73 m² per package insert, but clinical guidelines support use down to 20 mL/min/1.73 m² 1, 2

Benefits in CKD Stage 4

1. Kidney protection: Slows progression of kidney disease and reduces risk of kidney failure 1
2. Cardiovascular benefits: Reduces risk of heart failure hospitalization and cardiovascular death 1
3. Mortality reduction: Provides overall survival benefit 1

Clinical Management Algorithm

Before Initiation

1. Assess baseline renal function: Measure eGFR and albuminuria
2. Evaluate volume status: Consider reducing diuretic doses if patient at risk for hypovolemia 1
3. Review current medications:
   • If patient is on insulin or sulfonylureas and meeting glycemic targets, reduce doses by approximately 20% to prevent hypoglycemia 1, 2
   • Consider decreasing thiazide or loop diuretic dosages 1

Monitoring After Initiation

1. eGFR: Expect an initial reversible decline of 3-5 mL/min/1.73 m² within first 4 weeks; this is generally not a reason to discontinue therapy 2
2. Volume status: Monitor for signs of hypovolemia, especially in first few weeks 2
3. Glycemic control: More frequent blood glucose monitoring in patients on insulin or sulfonylureas 2
4. Follow-up schedule: Every 3-6 months for patients with eGFR 30-44 mL/min/1.73 m² 1

Important Precautions

When to Temporarily Withhold

• During periods of prolonged fasting
• Before major surgery (at least 3 days prior)
• During critical medical illness
• During acute illness with risk of dehydration 1, 3

Adverse Effects to Monitor

1. Euglycemic ketoacidosis: Educate patients about symptoms (nausea, vomiting, weakness) and that it can occur even with near-normal blood glucose levels 1
2. Genital mycotic infections: More common in women; educate about daily hygiene measures 1
3. Volume depletion: Monitor for hypotension, especially in patients on diuretics 1

Special Considerations

• SGLT2 inhibitors have minimal glucose-lowering effects in CKD stage 4 and are used primarily for kidney and cardiovascular benefits 1
• In patients with type 2 diabetes requiring additional glycemic control, consider GLP-1 receptor agonists as they retain glucose-lowering potency across all ranges of eGFR 1
• SGLT2 inhibitors are not recommended in kidney transplant recipients due to immunosuppression and potentially increased risk for infections 1

Common Pitfalls to Avoid

1. Discontinuing due to initial eGFR decline: The initial drop in eGFR is hemodynamic, expected, and generally reversible
2. Not adjusting concomitant medications: Failure to reduce doses of insulin, sulfonylureas, or diuretics can lead to hypoglycemia or volume depletion
3. Continuing during acute illness: Failure to temporarily withhold during acute illness can increase risk of ketoacidosis
4. Initiating below eGFR threshold: Starting when eGFR <20 mL/min/1.73 m² is not recommended

SGLT2 inhibitors represent a significant advancement in the management of CKD, with benefits extending beyond glycemic control to include kidney and cardiovascular protection, even in advanced CKD stages.