What are the guidelines for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as canagliflozin (canagliflozin) or dapagliflozin (dapagliflozin), in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

SGLT2 inhibitors are recommended for patients with chronic kidney disease (CKD) with an eGFR ≥20 mL/min/1.73m² and albuminuria ≥200 mg/g, regardless of diabetes status, to reduce CKD progression and cardiovascular events, as supported by the most recent guidelines 1.

Key Considerations

• The preferred agents are dapagliflozin (10 mg daily) and canagliflozin (100 mg daily), which have demonstrated significant kidney and cardiovascular benefits in large clinical trials 1.
• These medications should be initiated at full doses without titration and can be continued until dialysis or transplantation is needed, even if eGFR drops below 20 mL/min/1.73m² during treatment.
• Patients should be monitored for potential side effects including genital mycotic infections, volume depletion, and diabetic ketoacidosis (in those with diabetes) 1.

Mechanism of Action

• SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule, which reduces hyperfiltration and decreases intraglomerular pressure through tubuloglomerular feedback mechanisms.
• This action, along with other effects like reduced inflammation and oxidative stress, provides renoprotection independent of glucose-lowering effects.

Special Considerations

• These medications should be temporarily discontinued during acute illness, prolonged fasting, or surgical procedures to reduce the risk of complications.
• The use of SGLT2 inhibitors in patients with CKD and eGFR <20 mL/min/1.73m² is not well established, and their use in this population should be individualized based on the potential benefits and risks 1.

From the FDA Drug Label

DAPAGLIFLOZIN TABLETS a sodium-glucose cotransporter 2 (SGLT2) inhibitor, are indicated: • 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 (1)

Limitations of use: • 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. DAPAGLIFLOZIN TABLETS are likely to be ineffective in this setting based upon its mechanism of action. (1)

The guidelines for using SGLT2 inhibitors, such as dapagliflozin, in patients with Chronic Kidney Disease (CKD) are as follows:

• Indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with CKD 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, as they are likely to be ineffective in this setting.
• The recommended dosage is 10 mg orally once daily for all indications, including CKD.
• It is essential to assess renal function prior to initiation and then as clinically indicated, and to assess volume status and correct volume depletion before initiating dapagliflozin 2.

From the Research

Guidelines for Using SGLT2 Inhibitors in CKD

• The use of SGLT2 inhibitors, such as canagliflozin or dapagliflozin, is recommended as first-line therapy in patients with CKD, alongside statins, renin-angiotensin-aldosterone system inhibitors, and multifactorial risk factor management as indicated 3.
• SGLT2 inhibitors have been shown to slow the decline in kidney function and reduce the incidence of serious kidney events in patients with CKD 3, 4, 5.
• The pharmacokinetic parameters of SGLT2 inhibitors are slightly altered in patients with CKD, and dose adjustments may be necessary in patients with moderate CKD 6.
• SGLT2 inhibitors are contraindicated in patients with severe CKD, and prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor 6.

Benefits of SGLT2 Inhibitors in CKD

• SGLT2 inhibitors have been shown to reduce the risk of CKD progression, cardiovascular events, and all-cause mortality in patients with CKD 4, 5.
• The benefits of SGLT2 inhibitors are consistent in patients with and without type 2 diabetes, making them a promising therapeutic option for patients with diabetic and non-diabetic CKD 4, 5.
• SGLT2 inhibitors may also have a beneficial effect on albuminuria, kidney disease progression, and clinical stability in patients with Fabry disease and CKD 7.

Considerations for Using SGLT2 Inhibitors in CKD

• SGLT2 inhibitors remain significantly underutilized in the setting of CKD, and concerns regarding safety appear unfounded 3.
• The use of SGLT2 inhibitors in patients with CKD requires careful consideration of the potential benefits and risks, as well as individualized treatment planning 5.
• Further research is needed to fully understand the effects of SGLT2 inhibitors on kidney function and disease progression in patients with CKD, particularly in those with rare genetic disorders such as Fabry disease 7.