What are the indications for prescribing Forxiga (dapagliflozin) when the microalbumin to creatinine ratio is elevated, indicating early kidney damage?

Indications for Prescribing Forxiga (Dapagliflozin) with Elevated Microalbumin-to-Creatinine Ratio

Forxiga (dapagliflozin) is indicated for patients with elevated microalbumin-to-creatinine ratio of 4.5 mg/mmol as it reduces the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression.

Understanding Microalbuminuria

• Microalbuminuria is defined as urinary albumin excretion of 30-299 mg/24h or 30-299 mg/g creatinine (3-29 mg/mmol) on a random spot urine sample 1, 2
• A microalbumin-to-creatinine ratio of 4.5 mg/mmol falls within the moderately increased albuminuria range (3-29 mg/mmol), indicating early kidney damage 1
• Diagnosis requires confirmation with 2 out of 3 abnormal specimens collected within a 3-6 month period due to day-to-day variability in urinary albumin excretion 1, 2
• Transient elevations can occur with exercise, infection, fever, heart failure, marked hyperglycemia, hypertension, urinary tract infections, and hematuria 1, 2

Specific Indications for Dapagliflozin in Patients with Microalbuminuria

FDA-Approved Indications

• Dapagliflozin is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 3
• It is also indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus with established cardiovascular disease or multiple cardiovascular risk factors 3
• The recommended dosage for chronic kidney disease is 10 mg orally once daily 3

Evidence Supporting Use in Patients with Microalbuminuria

• The DAPA-CKD trial demonstrated that dapagliflozin significantly reduced the risk of kidney failure, cardiovascular death, and all-cause mortality in patients with chronic kidney disease with albuminuria (UACR ≥200 mg/g), regardless of diabetes status 4
• Dapagliflozin has been shown to reduce albuminuria by 21-38% in patients with type 2 diabetes and chronic kidney disease 5
• Real-world data from 93 Italian renal clinics showed that dapagliflozin reduced albuminuria by 25.1% in CKD patients, with 48.3% of patients achieving ≥30% reduction in albuminuria 6

Patient Selection Algorithm for Dapagliflozin

Step 1: Confirm Persistent Microalbuminuria

• Verify elevated microalbumin-to-creatinine ratio with at least 2 out of 3 specimens over 3-6 months 1
• Rule out transient causes of microalbuminuria (exercise, infection, fever, heart failure, marked hyperglycemia) 1, 2

Step 2: Assess Renal Function

• Measure eGFR prior to initiation of dapagliflozin 3
• For glycemic control in type 2 diabetes, dapagliflozin is recommended for patients with eGFR ≥45 mL/min/1.73m² 3
• For kidney protection, dapagliflozin can be used in patients with eGFR as low as 25 mL/min/1.73m² based on the DAPA-CKD trial 4

Step 3: Evaluate Cardiovascular Risk

• Assess for established cardiovascular disease or multiple cardiovascular risk factors 3
• Dapagliflozin provides cardiovascular protection regardless of baseline cardiovascular disease status 7

Step 4: Consider Concomitant Medications

• Ensure patient is on standard kidney protective therapy (ACE inhibitor or ARB) 1
• Dapagliflozin provides additional kidney protection when added to ACE inhibitor or ARB therapy 5

Safety Considerations

• Assess volume status before initiating dapagliflozin; correct volume depletion if present 3
• Monitor renal function after initiation as dapagliflozin can cause an acute reduction in eGFR that is generally not associated with adverse outcomes 8
• The risk of adverse events is low (2% discontinuation rate in real-world studies) with urinary tract infections and acute kidney injury being the most common adverse events 6
• Dapagliflozin has demonstrated safety in patients with CKD regardless of diabetes status 4

Monitoring After Initiation

• Monitor eGFR after initiation and periodically thereafter 3
• Continue monitoring urinary albumin-to-creatinine ratio every 6 months to assess treatment response 1
• A reduction in albuminuria of ≥30% is considered a positive response to therapy 1, 6
• Older age, female sex, use of mineralocorticoid receptor antagonists, higher baseline eGFR, and higher baseline albuminuria are predictors of better albuminuria reduction 6