What is the recommended dosage of Dapagliflozin (SGLT2 inhibitor) for a patient with proteinuria due to Glomerulonephritis (GN) and potential underlying kidney impairment?

Dapagliflozin Dosage for Proteinuria in Glomerulonephritis

The recommended dosage of dapagliflozin for proteinuria in glomerulonephritis is 10 mg orally once daily, provided the eGFR is ≥25 mL/min/1.73 m², as first-line therapy consists of maximally tolerated ACE inhibitor or ARB, not SGLT2 inhibitors. 1

Critical Context: SGLT2 Inhibitors Are NOT First-Line for GN

The KDIGO 2021 guidelines for glomerular diseases do not recommend SGLT2 inhibitors as first-line therapy for proteinuria in glomerulonephritis. 2 ACE inhibitors or ARBs uptitrated to maximally tolerated doses remain the cornerstone of proteinuria management in GN. 2

When to Consider Dapagliflozin in GN

SGLT2 inhibitors may be considered as add-on therapy in the following scenarios:

• Persistent proteinuria despite maximally tolerated ACE inhibitor/ARB therapy (typically ≥500 mg/day after 3-6 months of optimized supportive care) 3
• Patients with adequate kidney function (eGFR ≥25 mL/min/1.73 m²) 1
• As adjunctive renoprotection in patients already on standard immunosuppression and RAS blockade 3

Specific Dosing Recommendations

Standard Dosing for Renal Protection

• 10 mg orally once daily for reducing risk of sustained eGFR decline, ESKD, cardiovascular death, and hospitalization for heart failure in patients with CKD at risk of progression 1
• This dose applies when eGFR is ≥25 mL/min/1.73 m² 1

eGFR-Based Dosing Thresholds

• eGFR ≥25 mL/min/1.73 m²: Initiate at 10 mg once daily 1
• eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin 1
• If eGFR falls below 25 mL/min/1.73 m² during treatment: May continue 10 mg once daily to reduce risk of eGFR decline, ESKD, cardiovascular death, and heart failure hospitalization 1

Important Distinction from Diabetes Dosing

For glycemic control in diabetes, dapagliflozin is not recommended when eGFR <45 mL/min/1.73 m², but for renal protection in CKD (including GN), the threshold is eGFR ≥25 mL/min/1.73 m². 2, 1

Evidence Supporting Use in Non-Diabetic GN

Proteinuria Reduction

A 2023 randomized controlled trial in non-diabetic glomerulonephritis patients showed that empagliflozin (25 mg daily) as add-on to maximal RAAS blockade and immunosuppression resulted in significantly greater proteinuria reduction compared to placebo (median -77% vs -48%, p=0.002). 3

Contrasting Evidence

The DIAMOND trial (2020) found that 6-week treatment with dapagliflozin 10 mg daily did not significantly reduce proteinuria in non-diabetic CKD patients (difference 0.9%, 95% CI -16.6 to 22.1, p=0.93). 4 However, this was a short-term crossover study, and longer-term benefits on hard renal outcomes have been demonstrated. 5

Long-Term Renal Protection

The DAPA-CKD trial (2021) demonstrated that dapagliflozin 10 mg daily reduced the risk of kidney failure, cardiovascular death, and hospitalization for heart failure in patients with CKD (with or without diabetes), regardless of cardiovascular disease history (HR 0.61,95% CI 0.48-0.78 in primary prevention; HR 0.61,95% CI 0.47-0.79 in secondary prevention). 5

Pre-Treatment Assessment

Before initiating dapagliflozin: 1

• Assess renal function (eGFR must be ≥25 mL/min/1.73 m²)
• Assess volume status and correct volume depletion before starting
• Ensure patient is on maximally tolerated ACE inhibitor or ARB as per KDIGO guidelines 2

Expected Acute eGFR Changes

• An acute reversible decline in eGFR of up to 10% within 2 weeks is expected and not harmful 6
• Patients experiencing this acute eGFR reduction actually had better long-term eGFR preservation (-1.58 mL/min/1.73 m²/year) compared to those without acute decline (-2.44 to -2.48 mL/min/1.73 m²/year) 6
• Do not discontinue dapagliflozin for acute eGFR decline alone unless accompanied by other safety concerns 6

Critical Safety Monitoring

Volume Depletion Risk

• Counsel patients to hold dapagliflozin during intercurrent illnesses (vomiting, diarrhea, fever) to prevent acute kidney injury 2, 7
• Consider proactive dose reduction of diuretics in high-risk patients 2

Diabetic Ketoacidosis Risk

• Educate patients about signs/symptoms for early recognition 2
• Withhold dapagliflozin at least 3 days prior to major surgery or procedures with prolonged fasting 1
• Institute a sick day protocol 2

Hypoglycemia

• Adjust background glucose-lowering agents (insulin or sulfonylureas) as appropriate if patient has diabetes 2

Integration with Standard GN Management

Dapagliflozin should be added only after optimizing: 2, 7

• ACE inhibitor or ARB to maximally tolerated dose (not just BP target)
• Blood pressure control to <120-130 mmHg systolic
• Dietary sodium restriction to <2.0 g/day (<90 mmol/day)
• Disease-specific immunosuppression where indicated

Common Pitfall to Avoid

Do not use dapagliflozin as a substitute for ACE inhibitor/ARB therapy in GN. The KDIGO 2021 guidelines emphasize that RAS blockade remains first-line therapy for proteinuria in glomerular diseases, and SGLT2 inhibitors are not mentioned as primary treatment. 2 SGLT2 inhibitors should be considered as adjunctive therapy for additional renoprotection, not as monotherapy for proteinuria reduction in GN. 3