SGLT2 Inhibition and Kidney Potassium Homeostasis

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Sodium-glucose transporter 2 (SGLT2) inhibitors are used to treat type 2 diabetes and heart failure.
• SGLT2 inhibition in the proximal tubule influences kidney potassium (K+) handling.
• Physiological changes suggest potential for both increasing and decreasing K+ excretion.

Approach:

• This review examines the physiological mechanisms by which SGLT2 inhibitors affect kidney K+ excretion.
• It analyzes clinical observations regarding plasma K+ concentration in patients treated with SGLT2 inhibitors.
• The review synthesizes data to explain the low incidence of dyskalemias despite theoretical risks.

Key Points:

• SGLT2 inhibitors can theoretically increase and decrease renal K+ excretion through various pathways.
• Clinical data show SGLT2 inhibitors rarely cause significant plasma K+ abnormalities.
• These drugs may offer protection against hyperkalemia, particularly in patients with reduced kidney function or on renin-angiotensin-aldosterone system inhibitors.

Conclusions:

• The opposing effects of SGLT2 inhibitors on K+ handling likely offset each other, explaining the rarity of dyskalemias.
• SGLT2 inhibitors appear to attenuate hyperkalemia risk more than they cause hypokalemia.
• Further human studies are needed to fully elucidate the determinants of K+ handling under SGLT2 inhibition.