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Endocrinol Metab : Endocrinology and Metabolism


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Gheun-Ho Kim 1 Article
Diabetes, obesity and metabolism
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis
Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung
Endocrinol Metab. 2023;38(4):359-372.   Published online July 24, 2023
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AbstractAbstract PDFPubReader   ePub   
When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.


Citations to this article as recorded by  
  • Results from a cross-specialty consensus on optimal management of patients with chronic kidney disease (CKD): from screening to complications
    Mustafa Arici, Samir Helmy Assaad-Khalil, Marcello Casaccia Bertoluci, Jason Choo, Yau-Jiunn Lee, Magdalena Madero, Guillermo Javier Rosa Diez, Vicente Sánchez Polo, Sungjin Chung, Teerawat Thanachayanont, Carol Pollock
    BMJ Open.2024; 14(3): e080891.     CrossRef
  • Chronic Kidney Disease and SGLT2 Inhibitors
    Eun Sil Koh, Sungjin Chung
    The Journal of Korean Diabetes.2024; 25(1): 16.     CrossRef
  • Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors
    Veraprapas Kittipibul, Zachary L. Cox, Supavit Chesdachai, Mona Fiuzat, JoAnn Lindenfeld, Robert J. Mentz
    Journal of the American College of Cardiology.2024; 83(16): 1568.     CrossRef
  • Synopsis of the Korean Society of Nephrology 2023 Practical Recommendations for the Management of Diabetic Kidney Disease
    Sungjin Chung
    The Korean Journal of Medicine.2023; 98(6): 270.     CrossRef
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