Can I start a Sodium-Glucose Linked Transporter 2 (SGLT-2) inhibitor in a patient with impaired renal function?

SGLT-2 Inhibitors in Patients with Renal Failure

SGLT-2 inhibitors can be initiated in patients with chronic kidney disease when eGFR is ≥20 mL/min/1.73 m², but should not be newly started when eGFR is below this threshold. 1

Patient Selection Based on Renal Function

SGLT-2 inhibitors demonstrate different efficacy and safety profiles depending on the degree of renal impairment:

eGFR-Based Recommendations:

• eGFR ≥20 mL/min/1.73 m²: SGLT-2 inhibitors are recommended for initiation 1
• eGFR <20 mL/min/1.73 m²: Do not initiate SGLT-2 inhibitors 1
• Already on therapy: Can continue SGLT-2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 1
• Dialysis patients: SGLT-2 inhibitors are not recommended 2

Important Clinical Considerations:

• Expect a reversible decrease in eGFR (3-5 mL/min/1.73 m²) after initiation, which is generally not an indication to discontinue therapy 1, 3
• The glucose-lowering efficacy decreases with declining renal function, particularly when eGFR <45 mL/min/1.73 m² 3, 4
• Despite reduced glycemic effects, cardiovascular and renal benefits persist in CKD patients 5

Monitoring and Management

Before Initiation:

1. Assess baseline renal function (eGFR and albuminuria)
2. Evaluate volume status and risk for hypovolemia
3. Review concomitant medications, especially diuretics and other antihyperglycemic agents

After Initiation:

1. Monitor renal function:
   • First 1-2 weeks after starting therapy
   • Periodically thereafter (every 3-6 months for moderate CKD)
2. Assess for volume depletion symptoms, especially in:
   • Patients on diuretic therapy
   • Elderly patients
   • Those with tenuous volume status or history of AKI 1, 3

Risk Mitigation:

• Consider reducing diuretic doses before starting SGLT-2 inhibitor if patient is at risk for hypovolemia 1
• Educate patients about symptoms of volume depletion and when to seek medical attention
• Instruct patients to temporarily withhold medication during:
  • Prolonged fasting
  • Surgery or procedures
  • Critical illness
  • Severe acute illness 1, 3

Special Considerations

Potential Benefits in CKD:

• Reduction in albuminuria 6, 5
• Slowed progression of kidney disease 7
• Cardiovascular risk reduction 1
• These benefits appear to be independent of glucose-lowering effects 6, 7

Mechanism in CKD:

• SGLT-2 inhibitors reduce hyperfiltration through tubuloglomerular feedback 6
• They decrease inflammatory and fibrotic responses in proximal tubular cells 6, 8
• Initial eGFR drop is hemodynamic and typically stabilizes over time 6

Contraindications and Cautions:

• Kidney transplant recipients (inadequate safety data, potentially increased infection risk) 1, 3
• History of recurrent urinary tract infections or genital mycotic infections 3
• Risk of ketoacidosis, particularly in insulin-deficient states 2
• Severe volume depletion risk 2

Practical Approach

1. Determine eGFR threshold:

   • If eGFR ≥20 mL/min/1.73 m²: Can initiate SGLT-2 inhibitor
   • If eGFR <20 mL/min/1.73 m²: Do not initiate

2. Choose appropriate agent:

   • Select SGLT-2 inhibitor with documented kidney or cardiovascular benefits
   • Consider specific eGFR thresholds for individual agents per prescribing information 2

3. Adjust concomitant medications:

   • If on insulin or sulfonylureas: Consider reducing dose by ~20% to prevent hypoglycemia 3
   • If on diuretics: Consider reducing dose to prevent volume depletion 1

4. Patient education:

   • Explain expected initial eGFR drop
   • Review sick day management
   • Discuss symptoms requiring medical attention (volume depletion, ketoacidosis)

SGLT-2 inhibitors represent an important therapeutic option for patients with CKD, offering benefits beyond glycemic control. While their glucose-lowering efficacy decreases with declining renal function, their cardio-renal protective effects make them valuable for CKD management when used appropriately within the recommended eGFR thresholds.