What are the considerations for using Farxiga (dapagliflozin) in patients with Chronic Kidney Disease (CKD)?

Farxiga (Dapagliflozin) in Chronic Kidney Disease

Dapagliflozin is strongly recommended for patients with CKD with eGFR ≥25 mL/min/1.73 m² regardless of diabetes status, as it significantly reduces the risk of kidney disease progression, cardiovascular death, and hospitalization for heart failure. 1, 2

Indications and Benefits

Dapagliflozin is FDA-approved for:

• Reducing the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD at risk of progression 2
• Reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure 2

Key Clinical Benefits in CKD:

• 39% reduction in the composite outcome of ≥50% eGFR decline, end-stage kidney disease, or renal/cardiovascular death (HR 0.61; 95% CI 0.51-0.72) 3
• 31% reduction in all-cause mortality (HR 0.69; 95% CI 0.53-0.88) 3
• Benefits observed regardless of diabetes status 4
• Number needed to treat to prevent one primary outcome event: 19 3

Dosing and Administration

• Starting dose: 10 mg orally once daily for CKD indication 2
• eGFR considerations:
  • For CKD indication: Initiate if eGFR ≥25 mL/min/1.73 m² 1, 2
  • If eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin may be continued for kidney and cardiovascular benefits until dialysis 1, 2
  • For glycemic control (if also treating diabetes): Not recommended for initiation if eGFR <45 mL/min/1.73 m² 1, 2

Patient Selection and Monitoring

Pre-initiation Assessment:

• Assess renal function (eGFR) 2
• Evaluate volume status and correct volume depletion before initiating 2

Monitoring:

• Monitor renal function after initiation, particularly in patients with impaired baseline renal function 5
• Expect an initial, reversible decline in eGFR (often >10%) within the first 2 weeks of treatment - this does not require discontinuation and is not associated with worse outcomes 6
• Institute sick day protocol (temporary discontinuation during acute illness) 1

Special Considerations

Acute eGFR Changes:

• An initial eGFR drop >10% occurs in approximately 49% of patients treated with dapagliflozin 6
• This initial drop is associated with better long-term kidney outcomes and does not increase adverse events 6

Contraindications/Limitations:

• Not recommended for CKD treatment in patients with polycystic kidney disease 2
• Not recommended for CKD patients requiring or with recent history of immunosuppressive therapy 2
• Temporarily withhold at least 3 days before major surgery or procedures with prolonged fasting 2

Adverse Events to Monitor:

• Genital mycotic infections (counsel on genital hygiene) 1
• Volume depletion (consider proactive dose reduction of diuretics in high-risk patients) 1
• Diabetic ketoacidosis (rare, but educate on signs/symptoms) 1
• Hypoglycemia (adjust other glucose-lowering medications as needed) 1

Comparison with Other SGLT2 Inhibitors

While multiple SGLT2 inhibitors show kidney benefits, dapagliflozin has the most robust evidence for use in CKD:

• Dapagliflozin: Studied specifically in CKD population with and without diabetes (DAPA-CKD trial) 3, 4
• Empagliflozin: Approved for use at eGFR ≥20 mL/min/1.73 m² for heart failure but has more restrictive labeling for CKD 1
• Canagliflozin: Studied in diabetic CKD (CREDENCE trial) but not in non-diabetic CKD 1

Clinical Pearls

• The benefits of dapagliflozin in CKD extend beyond glycemic control and are present in patients with and without diabetes 4
• The initial eGFR decline is hemodynamic, reversible, and associated with better long-term outcomes 6
• Dapagliflozin can be continued even if eGFR falls below the initiation threshold during treatment 1, 2
• Benefits are seen across different etiologies of CKD, including diabetic nephropathy, glomerulonephritides, and ischemic/hypertensive kidney disease 4

By incorporating dapagliflozin into the treatment regimen for appropriate CKD patients, clinicians can significantly improve both kidney and cardiovascular outcomes, ultimately reducing mortality and improving quality of life.