Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease

0563725 - FGÚ 2023 RIV CH eng J - Článek v odborném periodiku
Hojná, Silvie - Kotsaridou, Zoe - Vaňourková, Z. - Rauchová, Hana - Behuliak, Michal - Kujal, P. - Kadlecová, Michaela - Zicha, Josef - Vaněčková, Ivana
Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease.
Biomedicines. Roč. 10, č. 10 (2022), č. článku 2509. E-ISSN 2227-9059
Grant CEP: GA ČR(CZ) GA19-06199S
Institucionální podpora: RVO:67985823
Klíčová slova: SGLT-2 inhibition * proteinuria * uninephrectomized salt-loaded * two-kidney * one-clip hypertension * fawn-hooded hypertensive rat
Obor OECD: Physiology (including cytology)
Impakt faktor: 4.7, rok: 2022
Způsob publikování: Open access
https://www.mdpi.com/2227-9059/10/10/2509

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.
Trvalý link: https://hdl.handle.net/11104/0336017