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

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 (α SMA) 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.