Gliflozins (sodium-glucose transporter-2 inhibitors) exhibited renoprotective effects not only in diabetic but also in non-diabetic patients with
chronic kidney disease (CKD). Controversial results were reported in experimental non-diabetic models of CKD. Therefore, we examined
empagliflozin effects in three CKD models, namely, in fawn-hooded hypertensive (FHH) rats, uninephrectomized
salt-loaded (UNX + HS) rats, and in rats with
Goldblatt hypertension (two-kidney, one-clip 2K1C) that were either untreated or treated with
empagliflozin (10 mg/kg/day) for eight weeks. Plethysmography blood pressure (BP) was recorded weekly, and renal parameters (
proteinuria, plasma
urea,
creatinine clearance, and
sodium excretion) were analyzed three times during the experiment. At the end of the study, blood pressure was also measured directly. Markers of oxidative stress (
TBARS) and
inflammation (MCP-1) were analyzed in kidney and plasma, respectively.
Body weight and visceral adiposity were reduced by
empagliflozin in FHH rats, without a significant effect on BP. Experimentally induced CKD (UNX + HS and 2K1C) was associated with a substantial increase in BP and relative heart and kidney weights.
Empagliflozin influenced neither visceral adiposity nor BP in these two models. Although
empagliflozin increased
sodium excretion, suggesting effective SGLT-2 inhibition, it did not affect diuresis in any experimental model. Unexpectedly,
empagliflozin did not provide renoprotection because
proteinuria, plasma
urea, and plasma
creatinine were not lowered by
empagliflozin treatment in all three CKD models. In line with these results,
empagliflozin treatment did not decrease
TBARS or MCP-1 levels in either model. In conclusion,
empagliflozin did not provide the expected beneficial effects on kidney function in experimental models of CKD.