Sodium-glucose cotransporter 2 inhibitors and inflammation in chronic kidney disease: Possible molecular pathways

J Cell Physiol. 2018 Jan;234(1):223-230. doi: 10.1002/jcp.26851. Epub 2018 Aug 4.

Abstract

Clinical trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and canagliflozin) have shown a decrease in the progression of chronic kidney disease (CKD). SGLT2 inhibitors represent a new category of oral antidiabetic agents that can also reduce systolic and diastolic blood pressure, as well as serum uric acid, and improve the glomerular filtration rate. Apart from affecting renal hemodynamics and glycotoxicity, evidence suggests that SGLT2 inhibitors may be renoprotective due to their effects on inflammation in renal tissues. Inflammatory responses play a prominent role in the pathophysiology of CKD as several structural and functional disorders of renal failure are strongly related to the overproduction of proinflammatory mediators. The present review discusses the anti-inflammatory properties of SGLT2 inhibitors. The different molecular pathways through which SGLT2 inhibitors may affect inflammation in the kidneys are also commented upon.

Keywords: canagliflozin; chronic kidney disease; dapagliflozin; empagliflozin; inflammation; renal failure; sodium-glucose cotransporter 2 inhibitors.

Publication types

  • Review

MeSH terms

  • Benzhydryl Compounds / therapeutic use
  • Blood Pressure / drug effects
  • Canagliflozin / therapeutic use
  • Disease Progression
  • Glomerular Filtration Rate / drug effects
  • Glucose / metabolism
  • Glucosides / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / pathology
  • Sodium-Glucose Transporter 2 / drug effects
  • Sodium-Glucose Transporter 2 / genetics*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Uric Acid / blood

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin
  • dapagliflozin
  • Uric Acid
  • empagliflozin
  • Glucose