title: [Prevention of diabetic nephropathy: from bench to bedside].
abstract: The early phases of diabetic nephropathy are characterized by an increase of GFR that, according to the tubular hypothesis, is secondary to alterations of proximal tubules. Experimental studies have in fact shown that hyperglycemia induces an increase in proximal re-absorption due to hypertrophy of tubular cells with consequent increment of sodium-glucose co-transport. The increased re-absorption in turn causes a reduction of the distal delivery of solutes and, through activation of tubuloglomerular feedback, an increase in single- nephron GFR. The resulting hyper-filtration has been proposed as a main risk factor for progression of diabetic renal disease. Limiting this early alteration may therefore represent a useful strategy for the prevention of diabetic nephropathy, that represents the major cause of ESRD in the western world today. Dapagliflozin, a competitive and highly selective inhibitor of sodium-glucose co-transport, reduces proximal tubular glucose re-absorption, increases renal glucose excretion, and reduces hyperglycemia in a dose-dependent manner. This singular mechanism of action may also have a limiting effect on diabetic hyper-filtration. Clinical trials are therefore warranted to evaluate the reno-protective efficacy of this drug in the long term.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Liberti
authors.forename: Adelia
authors.initials: A
authors.lastname: Sagliocca
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmisano
authors.forename: Laura
authors.initials: L
authors.lastname: Pirro
authors.forename: Michele
authors.initials: M
authors.lastname: Provenzano
authors.forename: Roberto
authors.initials: R
authors.lastname: Minutolo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: Luca
authors.initials: L
authors.lastname: De Nicola
mesh_terms: D000804:Angiotensin II / Q000032:analysis; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D057170:Translational Research, Biomedical
chemical_list: C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000804:Angiotensin II