Dapagliflozin in End-Stage Renal Disease (ESRD)
Dapagliflozin should NOT be initiated in patients with ESRD on dialysis, but may be continued if already established on therapy prior to reaching dialysis, though evidence for benefit in dialysis patients remains investigational.
Key Recommendations by eGFR Status
For Patients NOT Yet on Dialysis
Initiation is NOT recommended once eGFR falls below 20-25 mL/min/1.73 m², but continuation is reasonable if the patient was already taking dapagliflozin and tolerating it well 1, 2.
- Dapagliflozin initiation threshold: Do not start if eGFR <25 mL/min/1.73 m² for diabetes indication 1
- For CKD/heart failure indications: Do not start if eGFR <20 mL/min/1.73 m² 1
- Continuation strategy: If already on dapagliflozin when eGFR drops below initiation thresholds, continue the medication for kidney and cardiovascular benefits until dialysis is initiated 1
The FDA label explicitly states that dapagliflozin is not for use to improve blood sugar control in people with type 2 diabetes who have moderate to severe kidney problems, because it may not work 3. However, the cardiovascular and kidney protective benefits persist even at very low eGFR levels.
For Patients Already on Dialysis (True ESRD)
There is currently NO established indication for dapagliflozin in patients on maintenance dialysis. The evidence base is limited to ongoing safety trials 4, 5:
- The DARE-ESKD-2 trial is investigating cardiovascular effects in dialysis patients but results are pending 4
- A small safety study of empagliflozin (a related SGLT2 inhibitor) in 17 hemodialysis patients showed acceptable short-term safety but no efficacy data 5
- Guidelines do not recommend initiation or continuation once dialysis begins
Clinical Rationale
The glucose-lowering efficacy of SGLT2 inhibitors diminishes as kidney function declines because these drugs work by blocking glucose reabsorption in the proximal tubule 1. However, the cardiovascular and kidney protective benefits are preserved even at eGFR as low as 20 mL/min/1.73 m² 1, 2.
Key trial evidence supporting use down to eGFR 20 mL/min/1.73 m²:
- DAPA-CKD trial: Demonstrated clear efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73 m² 1
- EMPA-KIDNEY trial: Showed efficacy down to eGFR 20 mL/min/1.73 m² 1, 2
- Trial protocols specified continuation even when eGFR fell below initiation thresholds 1
Recent observational data suggests dapagliflozin may slow eGFR decline even in patients with baseline eGFR <25 mL/min/1.73 m² 6, but this does not extend to dialysis patients.
Safety Considerations in Advanced CKD
When continuing dapagliflozin as patients approach ESRD:
- Monitor for volume depletion: Risk of dehydration, orthostatic hypotension, and acute kidney injury 3
- Ketoacidosis risk: Can occur even with normal blood glucose; educate patients on symptoms (nausea, vomiting, abdominal pain, fatigue) 3
- Genital mycotic infections: More common in advanced CKD 1
- Hypoglycemia: Adjust insulin or sulfonylurea doses as needed 1
- Sick day protocol: Hold dapagliflozin during acute illness 1
Practical Algorithm
- eGFR ≥25 mL/min/1.73 m²: May initiate dapagliflozin 10 mg daily for CKD, heart failure, or diabetes with albuminuria
- eGFR 20-24 mL/min/1.73 m²: Do not initiate for diabetes; may initiate for CKD with albuminuria or heart failure
- eGFR <20 mL/min/1.73 m² but not on dialysis: Do not initiate; continue if already taking and tolerating well
- On dialysis: Discontinue dapagliflozin (no evidence of benefit; participation in clinical trials may be appropriate)
The key distinction is that ESRD on dialysis is fundamentally different from advanced CKD not yet requiring dialysis—the former has no established role for SGLT2 inhibitors outside of research settings.