Expected GFR Trajectory with Dapagliflozin in Advanced CKD
The initial GFR decline from 30 to 25 ml/min is an expected hemodynamic response to dapagliflozin that typically occurs within the first 1-4 weeks of treatment, and this patient should continue the medication as the GFR will stabilize at this new baseline and then decline more slowly than it would have without treatment—however, GFR will not "rise to normalcy" as dapagliflozin slows but does not reverse chronic kidney disease progression. 1, 2
Understanding the Initial GFR Dip
An acute, reversible decline in eGFR of 3-5 mL/min/1.73 m² is expected within the first 1-4 weeks after initiating dapagliflozin, representing a hemodynamic effect rather than kidney injury. 1, 3
In the DAPA-CKD trial, 49.4% of patients experienced an acute eGFR reduction >10% within 2 weeks of starting dapagliflozin, which is a normal physiologic response. 2
This initial dip occurs because dapagliflozin reduces intraglomerular pressure by blocking sodium-glucose reabsorption in the proximal tubule, leading to afferent arteriolar vasoconstriction through tubuloglomerular feedback. 1, 4
The decline from 30 to 25 ml/min (a 17% reduction) falls within the expected range and should not prompt discontinuation of therapy. 2
Timeline for GFR Stabilization
GFR typically stabilizes by week 4-6 after initiation and remains stable thereafter, not returning to the pre-treatment baseline but plateauing at the new lower level. 3, 4
In clinical trials, mean eGFR showed small transient reductions at week 1, returned to near baseline values by week 24, and remained stable through week 102. 3
After the initial dip, patients on dapagliflozin experience significantly slower long-term eGFR decline compared to placebo: those with an acute eGFR reduction >10% had a subsequent decline of only -1.58 ml/min/1.73 m²/year versus -3.27 ml/min/1.73 m²/year in the placebo group. 2
Critical Point: GFR Will Not Return to "Normalcy"
Dapagliflozin slows the progression of chronic kidney disease but does not reverse existing kidney damage or restore GFR to normal levels. 1, 5
The medication reduces the rate of sustained eGFR decline by approximately 50% compared to placebo, but the patient's baseline kidney disease remains. 1, 2
In the DELIVER trial, dapagliflozin attenuated eGFR decline by 1.4 mL/min/1.73 m²/year compared to placebo, demonstrating preservation rather than restoration of kidney function. 5
Clinical Management Algorithm
Week 0-2 (Current situation):
- The drop from 30 to 25 ml/min is expected and appropriate. 2
- Continue dapagliflozin 5mg daily without dose adjustment, as guidelines support continuation even when eGFR falls below 25 ml/min during treatment. 1
Week 2-6:
- Recheck eGFR within 1-2 weeks to confirm stabilization. 1
- Expect GFR to plateau around 23-27 ml/min range. 3, 4
- Assess volume status and reduce diuretic doses if signs of hypovolemia develop. 1
Beyond 6 weeks:
- Monitor eGFR every 3-6 months. 1
- Expect a much slower rate of decline (approximately -1.5 to -2 ml/min/year) compared to the -3 to -4 ml/min/year that would occur without dapagliflozin. 2
Common Pitfalls to Avoid
Do not discontinue dapagliflozin solely because eGFR fell below 25 ml/min, as cardiovascular and renal protective benefits persist even at this level, and the medication can be continued until dialysis is required. 1, 6
Do not expect GFR to return to 30 ml/min or higher—this represents unrealistic expectations about the medication's mechanism of action. 3, 5
Do not interpret the initial dip as medication failure or kidney injury—paradoxically, patients experiencing a larger acute eGFR reduction actually had better long-term renal outcomes in clinical trials. 2
Ensure the patient is not volume depleted, as this can exacerbate the initial GFR decline beyond the expected hemodynamic effect. 1
Monitoring for Safety
Check for signs of volume depletion, particularly if the patient is on concurrent diuretics. 1
Monitor for genital mycotic infections (occurs in ~6% of patients) and urinary tract infections. 1
Educate the patient to temporarily discontinue dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea. 1
Be aware that euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels. 1