Is it appropriate to add Farxiga (dapagliflozin) to the treatment regimen of an elderly female patient with Stage 3B Chronic Kidney Disease (CKD), diabetes, and proteinuria?

Adding Farxiga (Dapagliflozin) in Stage 3B CKD with Diabetes and Proteinuria

Yes, you should add Farxiga (dapagliflozin) 10 mg once daily to this patient's regimen, as it provides robust cardiorenal protection with a 39% reduction in kidney disease progression and 29% reduction in cardiovascular death or heart failure hospitalization, even in patients with Stage 3B CKD. 1

Evidence-Based Rationale for Initiation

The American Diabetes Association provides Class I, Level A recommendations for SGLT2 inhibitors like dapagliflozin in patients with chronic kidney disease and diabetes when eGFR ≥20 mL/min/1.73 m² and albuminuria (UACR ≥200 mg/g). 1 Stage 3B CKD (eGFR 30-44 mL/min/1.73 m²) falls well within this therapeutic window.

Renal Protection Benefits

• Dapagliflozin reduces the primary composite outcome (≥50% sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51-0.72). 1
• The kidney-specific composite outcome is reduced by 44% (HR 0.56,95% CI 0.45-0.68). 1
• Dapagliflozin slows the rate of eGFR decline over time and reduces progression to end-stage renal disease. 1
• These benefits are independent of diabetes status and persist even when glycemic efficacy is reduced at lower eGFR levels. 1

Cardiovascular Protection Benefits

• Dapagliflozin reduces cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55-0.92). 1
• All-cause mortality is reduced by 31% (HR 0.69,95% CI 0.53-0.88). 1
• The 2020 American College of Cardiology consensus and 2024 European Society of Cardiology guidelines provide Class I, Level A recommendations for SGLT2 inhibitors in patients with diabetes and chronic kidney disease. 1

Proteinuria Reduction

• In the DAPA-CKD trial with median baseline UACR of 949 mg/g, dapagliflozin reduced geometric mean UACR by 29.3% overall. 2
• Among patients with UACR ≥300 mg/g at baseline, dapagliflozin increased the likelihood of regression to lower albuminuria stages (HR 1.81,95% CI 1.60-2.05). 2
• Larger reductions in UACR at day 14 were significantly associated with attenuated eGFR decline during subsequent follow-up. 2

Dosing Algorithm for Stage 3B CKD

For patients with Stage 3B CKD (eGFR 30-44 mL/min/1.73 m²), the recommended dose is dapagliflozin 10 mg once daily for cardiovascular and renal protection, with no dose adjustment required. 1, 3

Key Dosing Considerations

• The 10 mg dose is fixed for all cardiovascular and renal indications—no titration is required or recommended. 1
• Dapagliflozin should not be used for glycemic control when eGFR <45 mL/min/1.73 m² as it is likely ineffective due to its mechanism of action, but the 10 mg dose remains appropriate for cardiovascular and renal protection. 1, 3
• If eGFR subsequently falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg daily may be continued until dialysis is required. 1, 3

Pre-Initiation Assessment and Monitoring

Before Starting Dapagliflozin

• Assess volume status and correct volume depletion if present, particularly in elderly patients or those on diuretics. 1, 3
• Check baseline eGFR and UACR to document kidney function and proteinuria. 1
• Consider reducing concurrent diuretic doses to prevent excessive volume depletion. 1

Post-Initiation Monitoring

• Recheck eGFR within 1-2 weeks after initiation—an initial eGFR decrease of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected, transient, and reversible. 4, 1
• This hemodynamic dip does not indicate tubular injury and should not prompt discontinuation. 4
• Monitor for genital mycotic infections, which occur in approximately 6% of patients versus 1% on placebo. 1, 3

Critical Safety Precautions

Sick Day Management

• Educate the patient to withhold dapagliflozin during acute illness, particularly with reduced oral intake, fever, vomiting, or diarrhea. 1
• Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 1, 3
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness. 1

Monitoring for Adverse Events

• Monitor for euglycemic diabetic ketoacidosis, which can occur even with normal blood glucose levels—educate patients about symptoms of malaise, nausea, vomiting, or abdominal pain. 1
• Assess for signs of urinary tract infections and treat promptly if indicated. 3
• Monitor for volume depletion, particularly in elderly patients, those on diuretics, or those with low systolic blood pressure. 3

Common Pitfalls to Avoid

Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m², as cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 1 The landmark DAPA-CKD trial specifically enrolled patients with eGFR 25-75 mL/min/1.73 m², demonstrating consistent benefits across this entire range. 1

Do not withhold ACE inhibitors/ARBs when starting dapagliflozin—these medications work synergistically for renal protection. 1 However, use clinical judgment if simultaneously initiating or up-titrating multiple agents in patients with impaired renal function. 1

Do not reduce the dapagliflozin dose to 5 mg for cardiovascular or renal indications—all outcome trials used the fixed 10 mg dose. 1 The 5 mg dose is only appropriate as a starting dose for glycemic control in patients with eGFR ≥45 mL/min/1.73 m². 3