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

Abstract

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.

• Authors: Qiuyue Ma, Stefanie Steiger, Hans-Joachim Anders
• Journal: Physiological reports (Physiol Rep) Vol. 5 Issue 7 (Apr 2017) ISSN: 2051-817X [Electronic] United States
• PMID: 28364032 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• 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

Topics

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