SGLT2 Inhibitors: Electrolyte, Water Balance, and Stone Prevention Benefits Beyond Metabolic Effects

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have revolutionized the therapeutic landscape of cardiometabolic and renal diseases. Originally developed to lower blood glucose in type 2 diabetes by promoting glycosuria, these agents are now recognized for their profound, glucose-independent cardiorenal protective effects. Beyond their well-documented metabolic and hemodynamic benefits, emerging pharmacological evidence highlights their significant impact on tubular transport, electrolyte homeostasis, and water balance. By acting directly on the proximal tubule, SGLT2 inhibitors uniquely modulate the excretion and reabsorption of key ions and fluids. This distinct mechanism of action opens new pharmacological avenues for managing complex fluid and mineral imbalances, suggesting that their therapeutic utility in renal medicine extends far beyond standard metabolic regulation.The primary aim of this Research Topic is to explore and consolidate the latest clinical, translational, and mechanistic research regarding the targeted renal benefits of SGLT2 inhibitors in electrolyte and fluid management. We seek to clearly elucidate the underlying pharmacological mechanisms that drive these non-metabolic effects. By curating high-quality research, this collection aims to bridge the knowledge gap surrounding three critical clinical challenges: the correction of hypomagnesemia, the pharmacological management of the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), and the prevention of kidney stone formation (nephrolithiasis). Ultimately, this Topic endeavors to provide clinicians and researchers with actionable pharmacological insights to optimize SGLT2 inhibitor therapy for complex renal and electrolyte disorders.We welcome the submission of Original Research, Review, Mini-Review, and Clinical Trial articles that advance our understanding of the broader pharmacological utility of SGLT2 inhibitors in renal medicine. The scope of this Research Topic specifically focuses on, but is not limited to, the following core themes:• Correction of Hypomagnesemia: Mechanistic and clinical studies investigating how SGLT2 inhibitors alter tubular transport to enhance renal magnesium reabsorption, and their clinical efficacy in correcting hypomagnesemia in vulnerable patient populations.• SIADH Correction: Research exploring the unique osmotic diuretic and aquaretic properties of SGLT2 inhibitors, specifically focusing on their pharmacological mechanisms and clinical viability in correcting hyponatremia and managing SIADH.• Preventing Kidney Stone Formation (Nephrolithiasis): Studies assessing the impact of SGLT2 inhibitors on urinary lithogenic and inhibitory factors, alterations in urinary volume and pH, and long-term clinical outcomes related to stone prevention.• Translational Renal Pharmacology: Novel insights into the molecular pathways, receptor interactions, and tubular modifications induced by SGLT2 inhibition that directly govern renal water and mineral balance. Topic editors: Armando Luis Negri, Guillermo Rosa Diez Source: https://www.frontiersin.org/research-topics/77496/sglt2-inhibitors-electrolyte-water-balance-and-stone-prevention-benefits-beyond-metabolic-effects