SGLT2 Inhibitors Are Contraindicated in ESRD Patients
SGLT2 inhibitors should not be used in patients with end-stage renal disease (ESRD) or on dialysis as they are contraindicated in this population.
Contraindications for SGLT2 Inhibitors
- SGLT2 inhibitors are specifically contraindicated in patients with severe renal impairment, ESRD, or those on dialysis 1
- The FDA label for dapagliflozin (a representative SGLT2 inhibitor) clearly states it is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m² 2
- SGLT2 inhibitors work by inhibiting glucose reabsorption in the proximal renal tubules, making them ineffective in patients with severely impaired kidney function 3
Evidence-Based Recommendations for SGLT2 Inhibitors in CKD
- KDIGO 2022 guidelines recommend SGLT2 inhibitors for patients with type 2 diabetes, CKD, and an eGFR ≥20 ml/min per 1.73 m² (strong recommendation, 1A) 1
- Once initiated, it is reasonable to continue SGLT2 inhibitors even if eGFR falls below 20 ml/min per 1.73 m², unless not tolerated or kidney replacement therapy is initiated 1
- SGLT2 inhibitors have demonstrated kidney and cardiovascular benefits in patients with eGFR as low as 20 ml/min per 1.73 m² 1
Mechanism and Efficacy Considerations
- SGLT2 inhibitors reduce glucose reabsorption in the proximal tubule, which requires functioning nephrons to be effective 3
- In ESRD, there are insufficient functioning nephrons for SGLT2 inhibitors to exert their therapeutic effect 1
- The glucose-lowering efficacy of SGLT2 inhibitors decreases progressively with declining kidney function 1
Safety Concerns in ESRD
- There is limited evidence regarding the safety of SGLT2 inhibitors in dialysis patients, with ongoing trials still exploring this area 1
- Potential risks in ESRD patients include:
- Volume depletion and hypotension, particularly concerning in patients already at risk for hemodynamic instability 1
- Risk of euglycemic diabetic ketoacidosis may be increased in patients with severely impaired kidney function 1
- Limited efficacy due to the mechanism of action requiring functioning nephrons 3
Current Research and Future Directions
- There is limited data on dapagliflozin safety in patients who initiated dialysis during clinical trials, but not enough evidence to recommend use in patients already on kidney replacement therapy 1
- Ongoing trials are exploring potential benefits of SGLT2 inhibitors in dialysis and transplant patients, but results are not yet available to guide clinical practice 1
- Meta-analyses show SGLT2 inhibitors significantly reduce the risk of worsening kidney function and progression to ESRD in patients with CKD, but specifically in those with eGFR ≥20 ml/min/1.73 m² 4
Clinical Approach for Patients with Advanced CKD
- For patients with eGFR 20-45 ml/min/1.73 m², SGLT2 inhibitors are recommended, especially with albuminuria ≥200 mg/g 1
- For patients approaching ESRD (eGFR <20 ml/min/1.73 m²), consider continuing SGLT2 inhibitors if already initiated and well-tolerated 1
- For patients on dialysis or with ESRD, SGLT2 inhibitors should be discontinued as they are contraindicated in this population 1, 2