Impact of the Four Pillars on Electrolyte Derangements during State-of-the-Art Therapy for Diabetic Kidney Disease
Abstract
The pharmacological management of diabetic kidney disease (DKD) has shifted toward a "four-pillar" approach that offers robust cardiorenal protection. While traditional renin-angiotensin system (RAS) inhibitors carry well-documented electrolyte risks, the distinct electrolyte profiles of novel therapies-sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and non-steroidal mineralocorticoid receptor antagonists (nsMRAs)-warrant a comprehensive understanding. This review examines these drug-induced electrolyte derangements. SGLT2 inhibitors demonstrate a highly favorable safety profile; despite inducing osmotic diuresis, they are notably associated with a reduced risk of hyperkalemia. Similarly, GLP-1 RAs possess an exceptionally low risk of direct renal electrolyte wasting, with imbalances occurring primarily secondary to severe gastrointestinal intolerance. Conversely, nsMRAs, such as finerenone, introduce a mild risk of hyperkalemia, though their unique receptor selectivity significantly diminishes this risk compared to traditional steroidal mineralocorticoid receptor antagonists. Crucially, combining SGLT2 inhibitors and nsMRAs creates a physiological synergy that attenuates hyperkalemic adverse effects while maximizing antiproteinuric benefits. By integrating these complementary mechanisms alongside routine electrolyte monitoring, clinicians can safely sustain these indispensable combination therapies and optimize…
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