In adults with chronic kidney disease (eGFR ≥ 25 mL/min/1.73 m²) who are receiving an ACE inhibitor or angiotensin receptor blocker, how should dapagliflozin (10 mg orally once daily) be initiated, monitored, and when should it be discontinued?

Dapagliflozin in CKD: Initiation, Monitoring, and Discontinuation

In adults with CKD (eGFR ≥25 mL/min/1.73 m²) receiving RAS inhibition, initiate dapagliflozin 10 mg orally once daily for kidney and cardiovascular protection, regardless of diabetes status. 1, 2, 3

Initiation Protocol

Pre-Initiation Assessment

Before starting dapagliflozin, perform the following:

• Assess renal function: Confirm eGFR ≥25 mL/min/1.73 m² 3
• Evaluate volume status: Correct any volume depletion before initiation 3
• Consider diuretic adjustment: If the patient is at risk for hypovolemia, decrease thiazide or loop diuretic doses before starting dapagliflozin 1
• Counsel patients: Advise about symptoms of volume depletion and low blood pressure 1

Dosing by Indication

For CKD protection (non-glycemic indication):

• Dose: 10 mg orally once daily 3
• eGFR threshold for initiation: ≥25 mL/min/1.73 m² 3
• Do NOT initiate if eGFR <25 mL/min/1.73 m² 3

For glycemic control in type 2 diabetes:

• Start at 5 mg daily, may increase to 10 mg for additional glycemic control 3
• Not recommended for glycemic control if eGFR <45 mL/min/1.73 m² (ineffective for glucose lowering) 3

Who Should Receive Dapagliflozin

The strongest evidence supports use in:

• Type 2 diabetes + CKD + eGFR ≥20 mL/min/1.73 m² (Grade 1A recommendation) 1, 2
• Adults with CKD + eGFR ≥20 mL/min/1.73 m² + UACR ≥200 mg/g (Grade 1A recommendation) 2
• Adults with CKD + heart failure, regardless of albuminuria level (Grade 1A recommendation) 2

The landmark DAPA-CKD trial enrolled patients with eGFR 25-75 mL/min/1.73 m² and UACR 200-5000 mg/g, demonstrating a 39% relative risk reduction in the primary composite outcome (sustained eGFR decline ≥50%, ESKD, or renal/cardiovascular death) with a number needed to treat of 19 over 2.4 years 4.

Monitoring Strategy

Initial Monitoring (First 2-4 Weeks)

Expect and accept an acute eGFR dip:

• An acute eGFR decline of 2-3 mL/min/1.73 m² within the first 2 weeks is normal and expected 5, 6
• This acute decline is hemodynamic, reversible, and NOT harmful 1, 6
• Approximately 49% of patients experience >10% eGFR reduction in the first 2 weeks 6
• Do NOT discontinue dapagliflozin due to this acute eGFR dip 1, 6

What to monitor:

• Blood pressure (expect 3-4 mmHg systolic reduction) 7
• Volume status and symptoms of hypotension 1, 3
• eGFR (to document expected acute decline) 1
• Serum potassium 1

Ongoing Monitoring

Standard CKD monitoring intervals apply:

• Dapagliflozin initiation does not necessitate more frequent monitoring than standard CKD care 2
• The reversible eGFR decrease is generally not an indication to discontinue therapy 1, 2

Long-term benefit on eGFR slope:

• After the initial dip, dapagliflozin slows eGFR decline by approximately 1-2 mL/min/1.73 m²/year compared to placebo 5
• Greater benefit observed in patients with type 2 diabetes (2.26 mL/min/1.73 m²/year) versus without diabetes (1.29 mL/min/1.73 m²/year) 5

When to Continue Despite eGFR Decline

Once initiated, continue dapagliflozin even if eGFR falls below the initiation threshold:

• If eGFR drops below 25 mL/min/1.73 m² during treatment, continue dapagliflozin unless not tolerated or kidney replacement therapy is initiated 1, 2, 3
• If eGFR drops below 20 mL/min/1.73 m² during treatment, it is reasonable to continue 1, 2

This recommendation is based on the principle that patients already receiving dapagliflozin continue to derive kidney and cardiovascular benefit even as kidney function declines.

When to Temporarily Withhold

Withhold dapagliflozin during:

• Major surgery or procedures with prolonged fasting: Hold for at least 3 days prior 3
• Critical medical illness when patients are at greater risk for ketosis 1, 2
• Prolonged fasting for any reason 1, 2

Resume when:

• Patient is clinically stable and has resumed oral intake 3

When to Discontinue

Absolute indications to stop:

• Kidney replacement therapy (dialysis or transplant) is initiated 1, 2
• Serious hypersensitivity reaction (anaphylaxis, angioedema) 3
• Intolerable side effects 1, 2

Relative indications to consider discontinuation:

• Symptomatic hypotension not manageable with volume optimization 1
• Recurrent ketoacidosis (rare in CKD population without type 1 diabetes) 3

Do NOT discontinue for:

• Acute eGFR decline of 2-3 mL/min/1.73 m² in first 2 weeks 1, 6
• eGFR falling below 25 or even 20 mL/min/1.73 m² during treatment 1, 2, 3
• Mild volume depletion (manage with fluid optimization) 1

Special Populations and Contraindications

Do NOT use in:

• Polycystic kidney disease (not expected to be effective) 3
• Patients requiring or with recent history of immunosuppressive therapy for kidney disease 3
• Kidney transplant recipients (inadequately studied, potential infection risk) 1

Use with caution in:

• Patients with type 1 diabetes (markedly increased ketoacidosis risk) 3
• Patients with history of pancreatitis or pancreatic surgery (ketoacidosis risk) 3

Key Clinical Pearls

• The acute eGFR dip is a feature, not a bug: Patients experiencing >10% acute eGFR decline actually had better long-term kidney outcomes in DAPA-CKD, with slower chronic eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) 6
• Benefits extend beyond albuminuria: Real-world data suggest effectiveness even in patients with UACR <200 mg/g, with eGFR slope improvement of 1.07 mL/min/1.73 m²/year 8
• Age is not a barrier: Benefits are consistent across all age groups, including septuagenarians and octogenarians who comprised 25% of DAPA-CKD participants 9
• Combination with RAS inhibition is safe and additive: Nearly all DAPA-CKD participants were on RAS inhibitors; dapagliflozin provides additional benefit without increased serious adverse events 10
• Modest blood pressure reduction: Expect 3-4 mmHg systolic BP reduction, which contributes to cardiovascular benefit 7