From the Guidelines
SGLT2 inhibitors are not recommended for patients with End-Stage Renal Disease (ESRD) on dialysis due to limited evidence of their effectiveness and potential safety concerns. The KDOQI Work Group believes that there is not enough evidence to suggest that these medications are effective in patients receiving kidney replacement therapy 1. Although some studies, such as the DAPA-CKD trial, have shown that dapagliflozin may be safe to use in persons receiving dialysis, the US Food and Drug Administration (FDA) has only concluded that there were no safety signals, but the overall benefit of SGLT2 inhibitors in dialysis patients is still unclear 1.
The primary mechanism of action of SGLT2 inhibitors, preventing glucose reabsorption in the kidneys, is severely impaired in dialysis patients, making these medications ineffective for their primary purpose. Additionally, the pharmacokinetics of these drugs may be altered in end-stage renal disease, potentially leading to unpredictable effects or accumulation. Some of the cardiovascular and renal protective benefits seen with SGLT2 inhibitors in patients with functioning kidneys would not be applicable to dialysis patients.
Key considerations for the use of SGLT2 inhibitors in patients with ESRD on dialysis include:
- Limited evidence of effectiveness in patients receiving kidney replacement therapy
- Potential safety concerns, such as volume depletion and electrolyte imbalances
- Altered pharmacokinetics in end-stage renal disease
- Ineffective primary mechanism of action due to severely impaired kidney function
If glycemic control is needed for dialysis patients with diabetes, other medication classes such as insulin, certain DPP-4 inhibitors, or GLP-1 receptor agonists would be more appropriate options as they don't rely on kidney function for their mechanism of action. Ongoing trials are exploring the potential benefits of SGLT2 inhibitors in dialysis and transplant patients, but until more evidence is available, SGLT2 inhibitors should not be used as a first-line treatment for patients with ESRD on dialysis 1.
From the Research
Role of SGLT2 Inhibitors in ESRD Patients on Dialysis
- The use of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with End-Stage Renal Disease (ESRD) on dialysis is a topic of interest, with some studies suggesting potential benefits 2, 3, 4.
- SGLT2 inhibitors have been shown to increase ultrafiltration volume and hemoglobin levels in chronic peritoneal dialysis patients, although the effect on overall survival and urinary tract infection rates is unclear 2.
- In patients with type 2 diabetes mellitus and chronic kidney disease, SGLT2 inhibitors have been found to lower glycated hemoglobin, blood pressure, body weight, and albuminuria, while reducing the risk of cardiovascular death, nonfatal myocardial infarction, and heart failure 3.
- The protective effects of SGLT2 inhibitors in patients with chronic kidney disease may be attributed to several mechanisms, including a reduction in intraglomerular pressure, a diuretic effect, and a reduction in renal oxygen consumption 4.
- However, it is essential to note that the evidence for the use of SGLT2 inhibitors in ESRD patients on dialysis is limited, and more research is needed to fully understand their role in this population.
Key Findings
- SGLT2 inhibitors may increase ultrafiltration volume and hemoglobin levels in chronic peritoneal dialysis patients 2.
- SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease 3.
- The protective effects of SGLT2 inhibitors in patients with chronic kidney disease may be attributed to multiple mechanisms, including a reduction in intraglomerular pressure and a diuretic effect 4.
Studies on SGLT2 Inhibitors
- A study published in 2024 found that SGLT2 inhibitors increased ultrafiltration volume and hemoglobin levels in chronic peritoneal dialysis patients 2.
- A systematic review and meta-analysis published in 2019 found that SGLT2 inhibitors reduced the risk of cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease 3.
- A review published in 2022 discussed the protective effects of SGLT2 inhibitors in patients with chronic kidney disease, highlighting multiple potential mechanisms 4.