What is the role of Farxiga (dapagliflozin) in the treatment of Chronic Kidney Disease (CKD)?

Farxiga (Dapagliflozin) for Chronic Kidney Disease

Farxiga (dapagliflozin) should be used as a first-line therapy for patients with chronic kidney disease with eGFR ≥20 mL/min/1.73 m² regardless of diabetes status to reduce CKD progression and cardiovascular events. 1, 2

Mechanism and Benefits

Dapagliflozin is an SGLT2 inhibitor that provides significant kidney and cardiovascular protection through several mechanisms:

• Reduces intraglomerular pressure
• Blunts tubuloglomerular feedback
• Reduces oxidative stress in the kidney
• Decreases NLRP3 inflammasome activity 3

Evidence for CKD Management

The DAPA-CKD trial provides the strongest evidence for dapagliflozin use in CKD. This landmark study demonstrated:

• 39% reduction in the primary composite endpoint (≥50% sustained decline in eGFR, ESKD, CV or renal death) 2
• 44% reduction in kidney-specific outcomes (≥50% sustained eGFR decline, ESKD, or renal death) 2
• 29% reduction in cardiovascular death or hospitalization for heart failure 2
• 31% reduction in all-cause mortality 2

Importantly, these benefits were consistent across patients with and without type 2 diabetes 4, making dapagliflozin appropriate for all CKD patients regardless of diabetes status.

Patient Selection and Dosing

Dapagliflozin can be initiated in patients with:

• eGFR ≥20 mL/min/1.73 m² 1
• With or without albuminuria 1
• With or without type 2 diabetes 4
• With or without established cardiovascular disease 5

The recommended dose is 10 mg once daily 2.

Integration with CKD Management

For optimal CKD management with dapagliflozin:

1. For patients with diabetes and CKD:

   • Start dapagliflozin regardless of glycemic control 1
   • Can be used with or without metformin and RAS inhibitors 1
   • Continue as long as tolerated until dialysis or transplantation 1

2. For patients with non-diabetic CKD:

   • Dapagliflozin provides similar kidney and cardiovascular protection 4
   • Benefits extend across various CKD etiologies (glomerulonephritis, ischemic/hypertensive CKD, etc.) 4

3. For patients with CKD and cardiovascular disease:

   • Particularly beneficial for reducing heart failure hospitalizations 2
   • Provides cardiovascular protection regardless of baseline cardiovascular status 5

Clinical Considerations and Monitoring

• Safety profile: Generally well-tolerated with low risk of serious adverse events 4
• Common side effects: Increased urination and genitourinary infections 1
• Monitoring: Regular assessment of kidney function, but dapagliflozin can be continued even if eGFR falls below the initiation threshold 1

Key Practice Points

• Dapagliflozin should be initiated early in CKD management, regardless of diabetes status
• Benefits extend beyond glycemic control to include kidney protection, cardiovascular protection, and mortality reduction
• The drug can be safely used alongside other standard CKD therapies including RAS inhibitors
• Continue dapagliflozin as long as tolerated, even if eGFR falls below 20 mL/min/1.73 m², until kidney replacement therapy is initiated 1

Farxiga represents a paradigm shift in CKD management, offering substantial kidney and cardiovascular protection beyond traditional therapies, with benefits that extend to both diabetic and non-diabetic CKD populations.