title: Sodium-Glucose Cotransporter-2 Inhibition and the Glomerulus: A Review.
abstract: Blood glucose-lowering treatment options generally target insulin action or beta-cell function. In diabetes, expression of the sodium-glucose cotransporter-2 (SGLT2) genes is up-regulated and renal threshold increased, resulting in increased glucose reabsorption from glomerular filtrate, reducing urinary glucose excretion and worsening the hyperglycemic condition. The SGLT2 inhibitors (SGLT2i) are a novel class of anti-diabetic drugs that lower blood glucose levels through the suppression of renal glucose reabsorption thereby promoting renal glucose excretion. The efficacy of SGLT2i is reduced in renal impairment because the ability of glucose-lowering is directly proportional to glomerular filtration rate. On the other hand, ongoing research suggests that SGLT2i may offer potential nephroprotection in diabetes. The SGLT2i have been shown to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and the biochemical progression of chronic kidney disease. Additional mechanisms through which SGLT2i exert nephroprotection may include normalizing blood pressure and uricemia. This review explores this bidirectional relationship of the SGLT2i and the glomerulus. While SGLT2i exhibit reduced efficacy in later stages, they exhibit nephroprotective effects in early stages of renal impairment.
  
  
  
  Janssen India (Pharmaceutical division of Johnson & Johnson).
authors.affiliation: Department of Endocrinology, Bharti Hospital, Karnal, India. brideknl@gmail.com.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Medical Affairs, Janssen (Pharmaceutical Division of Johnson & Johnson), Mumbai, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Singh
authors.affiliation: Medical Affairs, Janssen (Pharmaceutical Division of Johnson & Johnson), Mumbai, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Nagrale
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects; D065667:Renal Elimination / Q000187:drug effects; D065608:Renal Reabsorption / Q000187:drug effects; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose
keywords: Chronic kidney disease; Diabetes mellitus; Endocrinology; Glomerular hyperfiltration; Glomerulus; Nephrology; Nephroprotection; SGLT2 inhibitors