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

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...

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Autores principales: Hojná, Silvie, Kotsaridou, Zoe, Vaňourková, Zdeňka, Rauchová, Hana, Behuliak, Michal, Kujal, Petr, Kadlecová, Michaela, Zicha, Josef, Vaněčková, Ivana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599022/
https://www.ncbi.nlm.nih.gov/pubmed/36289772
http://dx.doi.org/10.3390/biomedicines10102509
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author Hojná, Silvie
Kotsaridou, Zoe
Vaňourková, Zdeňka
Rauchová, Hana
Behuliak, Michal
Kujal, Petr
Kadlecová, Michaela
Zicha, Josef
Vaněčková, Ivana
author_facet Hojná, Silvie
Kotsaridou, Zoe
Vaňourková, Zdeňka
Rauchová, Hana
Behuliak, Michal
Kujal, Petr
Kadlecová, Michaela
Zicha, Josef
Vaněčková, Ivana
author_sort Hojná, Silvie
collection PubMed
description 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.
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spelling pubmed-95990222022-10-27 Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease Hojná, Silvie Kotsaridou, Zoe Vaňourková, Zdeňka Rauchová, Hana Behuliak, Michal Kujal, Petr Kadlecová, Michaela Zicha, Josef Vaněčková, Ivana Biomedicines Article 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. MDPI 2022-10-07 /pmc/articles/PMC9599022/ /pubmed/36289772 http://dx.doi.org/10.3390/biomedicines10102509 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hojná, Silvie
Kotsaridou, Zoe
Vaňourková, Zdeňka
Rauchová, Hana
Behuliak, Michal
Kujal, Petr
Kadlecová, Michaela
Zicha, Josef
Vaněčková, Ivana
Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title_full Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title_fullStr Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title_full_unstemmed Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title_short Empagliflozin Is Not Renoprotective in Non-Diabetic Rat Models of Chronic Kidney Disease
title_sort empagliflozin is not renoprotective in non-diabetic rat models of chronic kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599022/
https://www.ncbi.nlm.nih.gov/pubmed/36289772
http://dx.doi.org/10.3390/biomedicines10102509
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