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Abstract: FR-PO158

Sodium-Glucose Cotransporter 2 Inhibition Does Not Ameliorate Renal Progression in Adriamycin-Induced Nephropathy

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Cha, Jin Joo, Korea University, Ansan, Korea (the Republic of)
  • Lim, Jeong-Taek, Korea University, Ansan, Korea (the Republic of)
  • Yoo, Ji ae, Korea University, Ansan, Korea (the Republic of)
  • Ghee, Jungyeon, Korea University, Ansan, Korea (the Republic of)
  • Min, Hye sook, Wonkwang University Gunpo Hospital, Gunpo-si, Korea (the Republic of)
  • Cha, Dae R., Korea University, Ansan, Korea (the Republic of)
  • Kang, Young Sun, Korea University, Ansan, Korea (the Republic of)

Sodium-glucose cotransporter 2(SGLT2) inhibitors target SGLT2 in renal proximal tubules and promotes glycosuria in type 2 diabetic mellitus, resulting in lowering blood glucose. Clinical studies have shown that SGLT2 inhibitors attenuate the progression of diabetic nephropathy, which results were not merely associated with improved glucose control. To understand the related mechanisms, we investigated the effects of SGLT2 inhibitior dapagliflozin (DAPA) in a mouse model of adriamycin (ADX)-induced nephropathy.


ADX induced nephropathy model resulted in severe proteinuria and progressive glomerulosclerosis. Seven week old Balb/c mice were divided in five groups;1) control with vehicle, 2) control with DAPA 3mg, 3) ADX(11.5mg/kg) with vehicle, 4) ADX(11.5mg/kg) with DAPA 1mg, 5) ADX(11.5mg/kg) with DAPA 3mg. With ADX injection, DAPA was administered via gavage for 2 weeks. Molecular analyses using RT-PCR, western blot and immunohistochemistry were performed.


DAPA administration was associated with decreased systolic blood pressure (SBP) in control group, but not among ADX injected groups. DAPA administration did not alleviate proteinuria, glomerular sclerosis and interstitial fibrosis in the ADX-induced nephropathy. Also, there were no differences in the expressions of TGF-β , Smad2 and collagen IV in the renal cortex of ADX with DAPA groups compared to ADX control group. Expression of macrophage marker ED1 was significantly increased in the kidney of ADX control group. DAPA administration in ADX groups decreased macrophage infiltration in the renal medulla, whereas no significant difference was observed in the renal cortex. SGLT2 expressions in the kidney were decreased in DAPA groups as expected. Strangely, the expressions of SGLT2 increased in the medulla of ADX with DAPA groups.


SGLT2 inhibition with dapagliflozin had no effect on reduction in proteinuria and inflammatory changes in renal cortex of ADX-induced nephropathy. Our study suggest that SGLT2 inhibition may modulate inflammation in the renal medulla, which effect may have been masked by massive insult of cortex. More experimental studies on renal injury model is needed to clarify the underlying mechanisms.