title: Sodium-glucose cotransporter-2 inhibition and the potential for renal protection in diabetic nephropathy.
abstract: OBJECTIVE
  Renal hyperfiltration has been used as a surrogate marker for increased intraglomerular pressure in patients with diabetes mellitus. Previous human investigation examining the pathogenesis of hyperfiltration has focused on the role of neurohormones such as the renin-angiotensin-aldosterone system (RAAS). Unfortunately, RAAS blockade does not completely attenuate hyperfiltration or diabetic kidney injury. More recent work has therefore investigated the contribution of renal tubular factors, including the sodium-glucose cotransporter, to the hyperfiltration state, which is the topic of this review.
  
  
  RESULTS
  Novel sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce proximal tubular sodium reabsorption, thereby increasing distal sodium delivery to the macula densa, causing tubuloglomerular feedback, afferent vasoconstriction and decreased hyperfiltration in animals. In humans, SGLT2 inhibition was recently shown to reduce hyperfiltration in normotensive, normoalbuminuric patients with type 1 diabetes. In clinical trials of type 2 diabetes, SGLT2 is associated with significant renal effects, including modest, acute declines in estimated glomerular filtration rate followed by the maintenance of stable renal function, and reduced albuminuria.
  
  
  CONCLUSIONS
  Existing data are supportive of a potential renal-protective role for SGLT2 inhibition in patients with diabetes. Dedicated renal outcome trials are ongoing and have the potential to change the clinical practice.
authors.affiliation: Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marko
authors.initials: M
authors.lastname: Škrtić
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001559:Benzhydryl Compounds / Q000627:therapeutic use; D000068896:Canagliflozin; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005960:Glucosides / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D065608:Renal Reabsorption / Q000187:drug effects; D012982:Sodium, Dietary / Q000494:pharmacology; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D012982:Sodium, Dietary; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin; C570240:empagliflozin