Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease

Physiol Rep. 2017 Apr;5(7):e13228. doi: 10.14814/phy2.13228.


Sodium glucose transporter (SGLT)-2 inhibition has renoprotective effects in diabetic kidney disease. Whether similar effects can be achieved also in non-diabetic kidney disease is speculative. Chronic kidney disease was induced in C57BL/6N mice by feeding an oxalate-rich diet for 14 days, known to induce nephrocalcinosis-related tubular atrophy and interstitial fibrosis without directly affecting the glomerular compartment. Empagliflozin treatment started from day 0 of oxalate feeding had no effect on the decline of glomerular filtration rate, crystal deposition, blood urea nitrogen or serum creatinine levels on day 7 and 14. Tissue morphometry of tubular injury and kidney mRNA levels of kidney injury molecule-1 or tissue inhibitor of metalloproteinase-2 were comparable between empagliflozin- and vehicle-treated mice with oxalate nephropathy on day 7 and 14. Similarly, empagliflozin did not affect markers of interstitial fibrosis, including silver, alpha smooth muscle actin (αSMA) and collagen 1 staining, and mRNA levels of fibronectin-1, collagen 1α1, fibroblast-specific protein-1, and transforming growth factor (TGF)-β2 on day 7 and 14. Thus, the specific renoprotective mechanisms-of-action of SGLT2 inhibition in diabetic kidney disease do not apply to chronic oxalosis, a non-diabetic form of chronic kidney disease.

Keywords: Crystal; diabetic nephropathy; glomerulosclerosis; progression.

MeSH terms

  • Animals
  • Benzhydryl Compounds / pharmacology
  • Benzhydryl Compounds / therapeutic use*
  • Blood Urea Nitrogen
  • Disease Models, Animal
  • Glomerular Filtration Rate / drug effects
  • Glucosides / pharmacology
  • Glucosides / therapeutic use*
  • Hepatitis A Virus Cellular Receptor 1 / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Oxalic Acid
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Benzhydryl Compounds
  • Glucosides
  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Protective Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Tissue Inhibitor of Metalloproteinase-2
  • Oxalic Acid
  • empagliflozin