From the Guidelines
SGLT-2 inhibitors should be used in patients with chronic kidney disease (CKD) who have an estimated glomerular filtration rate (eGFR) of at least 20 mL/min/1.73m², as they significantly slow CKD progression, reduce the risk of kidney failure, cardiovascular events, and heart failure hospitalizations, as supported by the most recent and highest quality study 1.
Key Considerations
- The use of SGLT-2 inhibitors in CKD management is recommended for patients with an eGFR ≥20 mL/min/1.73m², regardless of the presence of diabetes, as stated in the 2022 guideline update 1.
- These medications are typically started at standard doses: empagliflozin 10 mg daily, dapagliflozin 10 mg daily, or canagliflozin 100 mg daily.
- SGLT-2 inhibitors work by blocking glucose reabsorption in the proximal tubule, which reduces hyperfiltration and decreases intraglomerular pressure, thereby providing kidney protection.
- Patients should be monitored for potential side effects including genital mycotic infections, urinary tract infections, and volume depletion, as noted in the consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.
Important Recommendations
- It is reasonable to continue an SGLT2i even if the eGFR falls below 20 mL/min/1.73m², unless it is not tolerated or kidney replacement therapy is initiated, as recommended in the KDIGO 2022 clinical practice guideline update 1.
- SGLT-2 inhibitors are contraindicated in patients with type 1 diabetes and those on dialysis, though research is ongoing regarding potential benefits in dialysis patients, as mentioned in the executive summary of the KDIGO 2022 clinical practice guideline update 1.
- The choice of an SGLT2i should prioritize agents with documented kidney or cardiovascular benefits and take eGFR into account, as stated in the practice point of the KDIGO 2022 clinical practice guideline update 1.
From the FDA Drug Label
To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 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. Not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for the treatment of kidney disease
SGLT2 inhibitors, such as dapagliflozin, should be used in Chronic Kidney Disease (CKD) to reduce the risk of:
- Sustained eGFR decline
- End stage kidney disease
- Cardiovascular death
- Hospitalization for heart failure in adults with CKD at risk of progression 2. However, they are not recommended for patients with:
- eGFR less than 45 mL/min/1.73 m2
- Polycystic kidney disease
- Recent history of immunosuppressive therapy for kidney disease 2.
From the Research
SGLT2 Inhibitors in Chronic Kidney Disease (CKD)
- SGLT2 inhibitors should be considered for patients with type 2 diabetes (T2D) and CKD having an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g 3
- The use of SGLT2 inhibitors is not limited to patients with T2D, as they have also shown to be effective in patients with non-diabetic CKD, reducing the risk of CKD progression and cardiovascular events 4, 5, 6
- Individualized treatment with SGLT2 inhibitors represents a promising therapeutic option for patients with both diabetic and non-diabetic CKD, and may soon be indicated for patients with CKD without albuminuria 4, 7, 6
Patient Selection and Initiation
- Patients with eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g are considered a high-risk group eligible for SGLT2 inhibitors 3
- SGLT2 inhibitor initiation is negatively correlated with age ≥ 65 years and recent hospitalization, and positively correlated with HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events 3
- Practical considerations for prescription of SGLT2 inhibitors include the anticipated acute decline in eGFR on initiation, initiating the lowest dosage used in clinical trials, volume status considerations, and adverse event mitigation 7
Clinical Implications
- SGLT2 inhibitors have been shown to reduce the risk of CKD progression, cardiovascular events, and all-cause mortality in patients with CKD, making them a valuable addition to the treatment landscape 4, 5, 6
- The use of SGLT2 inhibitors in patients with CKD may require a shift in the glucocentric approach, focusing on reducing renal events in addition to glycemic control 3