title: 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.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Steiger
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany hjanders@med.uni-muenchen.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019815:Oxalic Acid; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D020011:Protective Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D019815:Oxalic Acid; C570240:empagliflozin
keywords: Crystal; diabetic nephropathy; glomerulosclerosis; progression