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The kidneys reabsorb filtered glucose through the sodium\u2010glucose cotransporters sodium\u2010glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin\u2010angiotensin\u2010aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.<\/jats:p>","DOI":"10.1161\/jaha.120.018889","type":"journal-article","created":{"date-parts":[[2020,11,14]],"date-time":"2020-11-14T10:01:11Z","timestamp":1605348071000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6986-8885","authenticated-orcid":false,"given":"Edoardo","family":"Gronda","sequence":"first","affiliation":[{"name":"Programma Cardiorenale U.O.C. 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