Is dapagliflozin (Forxiga) safe to use in patients with end-stage Chronic Kidney Disease (CKD)?

Dapagliflozin in End-Stage Chronic Kidney Disease

Dapagliflozin can be safely used in patients with end-stage CKD for cardiorenal protection, but should not be initiated when eGFR is below 25 mL/min/1.73 m².

Indications and Efficacy in Advanced CKD

• Dapagliflozin is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 1
• The DAPA-CKD trial demonstrated significant benefits in patients with eGFR as low as 25 mL/min/1.73 m², with a 39% reduction in the primary composite outcome of sustained decline in eGFR, end-stage kidney disease, or death from renal or cardiovascular causes 2
• These benefits were consistent across all KDIGO risk categories, including those with very high risk (most severe) CKD 3
• The efficacy was demonstrated regardless of diabetes status - patients with and without diabetes showed similar benefits 2

Dosing Recommendations in End-Stage CKD

• For cardiorenal protection: Dapagliflozin 10 mg once daily can be used in patients with eGFR ≥25 mL/min/1.73 m² 1
• Initiation is not recommended in patients with eGFR <25 mL/min/1.73 m² 1
• If eGFR falls below 25 mL/min/1.73 m² during treatment, patients may continue dapagliflozin 10 mg daily to reduce the risk of eGFR decline, ESKD, cardiovascular death, and heart failure hospitalization 1
• For glycemic control: Dapagliflozin is not recommended when eGFR <45 mL/min/1.73 m² as it is likely ineffective for this purpose due to its mechanism of action 1

Safety Considerations

• The DAPA-CKD trial showed a favorable safety profile across all KDIGO risk categories, including those with very high-risk CKD 3
• Adverse events were similar between dapagliflozin and placebo groups, even in patients with the most advanced kidney disease 3
• Key safety considerations include:
  • Assess volume status before initiation and correct volume depletion if present 4
  • Withhold dapagliflozin for at least 3 days prior to major surgery or procedures requiring prolonged fasting 1
  • Monitor for potential adverse effects such as genital mycotic infections, urinary tract infections, volume depletion, and euglycemic diabetic ketoacidosis 4

Concomitant Medications

• Dapagliflozin can be safely used alongside other cardiovascular medications commonly prescribed in CKD patients 5
• The DAPA-CKD trial demonstrated consistent benefits regardless of baseline use of:
  • Renin-angiotensin-aldosterone system inhibitors
  • Calcium channel blockers
  • Beta-blockers
  • Diuretics
  • Antithrombotic agents
  • Lipid-lowering medications 5

Clinical Decision Algorithm

1. For patients with eGFR ≥25 mL/min/1.73 m²:

   • Prescribe dapagliflozin 10 mg once daily for cardiorenal protection 1
   • Assess volume status before initiation 4

2. For patients with eGFR <25 mL/min/1.73 m²:

   • Do not initiate dapagliflozin 1
   • If patient is already on dapagliflozin and eGFR drops below 25 mL/min/1.73 m², continue treatment at 10 mg daily 1

3. For glycemic control specifically:

   • Do not use dapagliflozin for glycemic control when eGFR <45 mL/min/1.73 m² 1
   • Consider alternative agents such as DPP-4 inhibitors, GLP-1 receptor agonists, or insulin with appropriate dose adjustments 6

Key Takeaways

• Dapagliflozin provides significant cardiorenal protection in advanced CKD patients with eGFR as low as 25 mL/min/1.73 m² 2
• The benefits include reduced risk of kidney disease progression, cardiovascular events, and all-cause mortality 2
• While glycemic efficacy diminishes at lower eGFR levels, the cardiorenal protective effects are preserved 4
• The safety profile remains favorable even in patients with advanced kidney disease 3