What does improvement in Estimated Glomerular Filtration Rate (EGFR) after taking Dapagliflozin (Forxiga) indicate?

Improvement in EGFR After Dapagliflozin

Improvement in estimated glomerular filtration rate (eGFR) after taking dapagliflozin indicates significant renoprotective effects that reduce the risk of kidney disease progression, end-stage kidney disease, and cardiovascular mortality.

Initial eGFR Response Pattern

Dapagliflozin typically causes a characteristic biphasic effect on eGFR:

1. Initial acute decline phase:

   • A small, transient reduction in eGFR (approximately 2-3 mL/min/1.73 m²) occurs within the first 1-2 weeks of treatment 1, 2
   • This is a hemodynamic effect, not indicating kidney injury

2. Long-term preservation phase:

   • After the initial dip, eGFR stabilizes and shows a significantly slower rate of decline compared to patients not taking dapagliflozin
   • The DAPA-CKD trial demonstrated dapagliflozin slowed eGFR decline by 0.95 mL/min/1.73 m² per year compared to placebo 1

Clinical Significance of eGFR Improvement

The improvement in eGFR trajectory with dapagliflozin represents:

• Reduced risk of kidney failure progression: Dapagliflozin reduces the risk of sustained decline in eGFR of ≥50%, ESKD, or death from renal causes by 44% (HR 0.56,95% CI 0.45-0.68) 3, 4

• Cardiovascular protection: The medication reduces the composite of cardiovascular death or hospitalization for heart failure by 29% (HR 0.71,95% CI 0.55-0.92) 4, 3

• Mortality benefit: All-cause mortality is decreased in patients taking dapagliflozin compared to placebo (p<0.004) 4

Mechanism of Renoprotection

The improvement in eGFR with dapagliflozin likely results from multiple mechanisms:

• Reduction in intraglomerular pressure
• Decreased hyperfiltration
• Improved tubuloglomerular feedback
• Reduced inflammation and fibrosis
• Metabolic improvements (glycemic control, weight reduction)

Important Clinical Considerations

1. Do not discontinue due to initial eGFR dip:

   • The initial decrease in eGFR is expected and not a reason to stop therapy 4
   • KDIGO guidelines specifically note that "SGLT2i initiation or use does not necessitate alteration of frequency of CKD monitoring and the reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy" 4

2. Continue even with eGFR decline:

   • Guidelines recommend continuing dapagliflozin even if eGFR falls below initiation thresholds (as low as 20 mL/min/1.73 m²) unless not tolerated or kidney replacement therapy is initiated 4

3. Benefits extend beyond diabetes:

   • While initially developed for type 2 diabetes, dapagliflozin's renoprotective effects are seen in patients with CKD regardless of diabetes status 1, 5

Monitoring Recommendations

• Measure baseline eGFR before starting dapagliflozin
• Do not be alarmed by small decreases in eGFR (2-3 mL/min/1.73 m²) in the first 1-2 weeks
• Continue regular monitoring of kidney function as part of standard care
• Consider temporary withholding during periods of acute illness, prolonged fasting, or surgery 4

Patient Selection for Maximum Benefit

The greatest eGFR preservation benefits are seen in:

• Patients with higher baseline albuminuria (UACR ≥200 mg/g) 1
• Those with type 2 diabetes (though benefits extend to non-diabetics as well) 1
• Patients with eGFR ≥20 mL/min/1.73 m² 4

In conclusion, improvement in eGFR after taking dapagliflozin represents a significant clinical benefit that translates to reduced risk of kidney disease progression, cardiovascular events, and mortality. This medication should be considered a cornerstone therapy for patients with CKD, especially those with albuminuria, regardless of diabetes status.