J Korean Diabetes.  2024 Mar;25(1):16-25. 10.4093/jkd.2024.25.1.16.

Chronic Kidney Disease and SGLT2 Inhibitors

• Koh ES
• Chung S

• KMID: 2554117
• DOI: http://doi.org/10.4093/jkd.2024.25.1.16

Abstract

Sodium glucose cotransporter 2 (SGLT2) inhibitors were initially developed to enhance glycemic control in diabetic patients, but they have emerged as a promising treatment for individuals with chronic kidney disease (CKD) regardless of diabetic status. A collaborative meta-analysis of large-scale SGLT2 inhibitor trials has provided compelling evidence supporting recommendations for the use of these agents in CKD patients, regardless of their primary kidney disease diagnosis or whether they have diabetes. Notably, the kidney-protective benefits of SGLT2 inhibitors have been observed across various stages of CKD, including advanced stage 4 CKD, and across all levels of albuminuria. Given the robust evidence highlighting the benefits of SGLT2 inhibitors across a broad spectrum of CKD patients, these agents should be considered foundational therapy for CKD, in order to mitigate the progression to kidney failure and its associated complications. Although the beneficial effects of SGLT2 inhibitors may not be immediately apparent, they are expected to grow over time, potentially altering the prognosis for numerous CKD patients.

Keyword

Diabetes mellitus; Renal insufficiency, chronic; Sodium-glucose transporter 2 inhibitors

Figure

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  Fig. 1. Indications for initiating RAS and SGLT2 inhibitors in diabetic kidney disease. (A) Range of indications for initiating RAS inhibitors (red-colored boxes), and (B) SGLT2 inhibitors (blue-colored boxes) in diabetic kidney disease based on the KDIGO GFR and albuminuria categories for staging chronic kidney disease according to the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease [23] and the KSN 2023 Practical Recommendations for the Management of Diabetic Kidney Disease [24] are shown. (C) SGLT2 inhibitors may be initiated in patients with diabetic kidney disease with a normal range of albuminuria if they have an eGFR ≥ 20 mL/min/1.73 m². The dosage of RAS inhibitors should be reduced or discontinued only as a last resort in chronic kidney disease patients with symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms. Similarly, once an SGLT2 inhibitor is initiated, it should be continued even if the eGFR falls below 20 mL/min/1.73 m², unless it is not tolerated or kidney replacement therapy is initiated [22]. RAS, renin-angiotensin system; SGLT2, sodium glucose cotransporter 2; KDIGO, Kidney Disease: Improving Global Outcomes; GFR, glomerular filtration rate; KSN, Korean Society of Nephrology; eGFR, estimated glomerular filtration rate.

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  Fig. 2. Indications for initiating RAS and SGLT2 inhibitors in nondiabetic chronic kidney disease. (A) Range of indications for initiating RAS inhibitors (red-colored boxes), and (B) SGLT2 inhibitors (B, blue-colored boxes) in nondiabetic chronic kidney disease based on the KDIGO GFR and albuminuria categories for staging chronic kidney disease according to KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease [26] are shown. (C) SGLT2 inhibitors may be initiated in patients with nondiabetic chronic kidney disease even with albuminuria < 200 mg/g and eGFR 20∼45 mL/min/1.73 m², as well as in patients with albuminuria ≥ 200 mg/g and eGFR ≥ 20 mL/min/1.73 m², and then continued even if the eGFR falls below 20 mL/min/1.73 m², unless kidney replacement therapy is initiated. RAS, renin-angiotensin system; SGLT2, sodium glucose cotransporter 2; KDIGO, Kidney Disease: Improving Global Outcomes; GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate.

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