What is the role of Sodium-Glucose Linked Transporter 2 inhibitors (SGLT2i) in managing Chronic Kidney Disease (CKD)?

SGLT2 Inhibitors in Chronic Kidney Disease Management

SGLT2 inhibitors are strongly recommended for all patients with CKD and eGFR ≥20 mL/min/1.73 m² regardless of diabetes status, as they significantly reduce CKD progression, cardiovascular events, and mortality. 1

Indications and Benefits

SGLT2 inhibitors provide substantial benefits in CKD management:

• Mortality reduction: Decrease all-cause mortality by 24 per 1000 patients 1
• Kidney protection: Prevent 58 kidney failure events per 1000 patients 1
• Cardiovascular benefits: Reduce heart failure hospitalizations by 25 per 1000, myocardial infarctions by 32 per 1000, and strokes by 25 per 1000 patients 1

These benefits occur through multiple mechanisms:

• Reduction in intraglomerular pressure
• Decreased renal tubular glucose reabsorption
• Lower systemic blood pressure
• Reduced albuminuria
• Decreased oxidative stress in the kidney 1

Patient Selection and Initiation

Who Should Receive SGLT2i

• Patients with CKD and eGFR ≥20 mL/min/1.73 m² 2
• Both diabetic and non-diabetic CKD patients 1
• Highest priority: Patients with albuminuria (ACR ≥200 mg/g) 2

Dosing Guidelines

• Canagliflozin: 100 mg daily
• Dapagliflozin: 10 mg daily
• Empagliflozin: 10 mg daily 2

Monitoring After Initiation

1. Anticipate an initial, reversible decline in eGFR (hemodynamic effect) - this is not a reason to discontinue therapy 2
2. Monitor volume status, especially in patients on diuretics 2
3. Assess for adverse effects at follow-up visits 2

Continuation of Therapy

• Continue SGLT2i even if eGFR falls below the initiation threshold (20 mL/min/1.73 m²) 2
• Discontinue only if:
  • Patient is not tolerating treatment
  • Kidney replacement therapy is initiated 2

Combination Therapy

SGLT2 inhibitors should be used:

• As first-line therapy alongside RAS inhibitors (ACEi or ARB) 1
• Can be added to existing glucose-lowering regimens in diabetic patients 2
• Can be combined with GLP-1 receptor agonists for additional cardiorenal protection 1
• May be used with nonsteroidal mineralocorticoid receptor antagonists in appropriate patients 1

Managing Potential Adverse Effects

Volume Depletion

• Consider reducing diuretic doses before starting SGLT2i 2
• Monitor for symptoms of volume depletion 2
• Reassess volume status at follow-up visits 2

Diabetic Ketoacidosis

• Maintain at least low-dose insulin in insulin-requiring patients 2
• Implement a sick day protocol (temporarily withhold SGLT2i during illness) 2
• Monitor blood/urine ketones in high-risk patients 2
• Educate patients about signs/symptoms for early recognition 2

Genital Mycotic Infections

• Counsel patients on genital hygiene 2
• Risk is higher in women than men (6% vs 1% compared to placebo) 2
• Most infections are easily treated, but severe cases including Fournier gangrene have been reported 2

Hypoglycemia

• Risk is generally low with SGLT2i alone 2
• Consider adjusting doses of insulin or sulfonylureas when adding SGLT2i 2

Special Considerations

When to Temporarily Withhold SGLT2i

• During prolonged fasting
• Before/during surgery
• During critical medical illness
• During acute illness or excessive exercise 2

Contraindications

• eGFR <20 mL/min/1.73 m² (for initiation only) 2
• Kidney transplant recipients (due to immunosuppression) 2
• Polycystic kidney disease 1
• Patients requiring or with recent immunosuppressive therapy for kidney disease 1

Conclusion

SGLT2 inhibitors represent a significant advancement in CKD management, offering protection against disease progression and cardiovascular events while reducing mortality. Their benefits extend beyond glycemic control, making them valuable for both diabetic and non-diabetic CKD patients with eGFR ≥20 mL/min/1.73 m².