The aim: to assess the effects of SGLT2 inhibitor empagliflozin, DPP-4 inhibitor linagliptin, and their combination on structural changes in kidneys in a model of type 2 diabetic nephropathy. Eight-week-old male db/db diabetic mice (BKS.Cg-Dock7m+/+Leprdb/J) were treated with empagliflozine (10 mg/kg), linagliptin (10 mg/kg), combination of both agents, or placebo for 8 weeks. Nondiabetic heterozygous db/+ mice were used as control. Renal structural changes were analyzed quantitatively from the light and electron microscopic images. Both empagliflozin and linagliptin, either alone or in combination, attenuated mesangial expansion estimated by mesangial volume (p=0.00for empagliflozin, p=0.03 for linagliptin and combination). The width of glomerular basement membrane was diminished in all treated groups (all p<0.01). In diabetic mice, podocytopathy was manifested by the foot process effacement (p=0.03). Under treatment, the number of podocyte foot processes increased (p=0.003 for linagliptin, p=0.03 for empagliflozin and combination) and the width of podocyte foot processes decreased in all treated groups (p=0.003 for empagliflozin and linagliptin, p=0.001 for combintion). The number of endothelial fenestrae in glomerular capillaries was increased after the treatment (all p<0.01). The interaction between empagliflozin and linagliptin was significant for the number and width of podocyte foot processes, and the number of endothelial fenestrae (all p<0.01). The effects of both agents on structural changes were not associated with hypoglycemic activity. The obtained results demonstrate that empagliflozin and linagliptin ameliorate renal fibrosis and podocyte injury in a model of type 2 diabetic nephropathy.
A.I. Korbut: None. V. Klimontov: None. I. Taskaeva: None. N.P. Bgatova: None. I. Ishchenko: None. E.L. Zavjalov: None.