Head-to-head comparison of two SGLT-2 inhibitors on AKI outcomes in a rat ischemia-reperfusion model.

Animals Rats Acute Kidney Injury / drug therapy Benzhydryl Compounds / pharmacology Canagliflozin / pharmacology Cardiovascular Diseases / drug therapy Ischemia / drug therapy MicroRNAs / therapeutic use Reperfusion Sodium-Glucose Transporter 2 Inhibitors / pharmacology
Acute kidney injury Canagliflozin Empagliflozin Sodium-glucose cotransporter 2 inhibitors

Journal

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Titre abrégé: Biomed Pharmacother
Pays: France
ID NLM: 8213295

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 12 03 2022
revised: 23 06 2022
accepted: 28 06 2022
pubmed: 7 7 2022
medline: 9 9 2022
entrez: 6 7 2022
Statut: ppublish

Résumé

The CREDENCE trial testing canagliflozin and the EMPA-REG OUTCOME trial testing empagliflozin suggest different effects on acute kidney injury (AKI). AKI diagnosis was mainly made based on changes of serum creatinine (sCr) although this also reflect mode of action of SGLT-2 inhibitors. We analyzed both compounds in a rat AKI model. The renal ischemia-reperfusion injury (I/R) model was used. Four groups were analyzed: sham, I/R+placebo, I/R+canagliflozin (30 mg/kg/day), I/R+ empagliflozin (10 mg/kg/day). Glucose excretion was comparable in both treatment groups indicating comparable SGLT-2 inhibition. Comparing GFR surrogate markers after I/R (sCr and blood urea nitrogen (BUN)), sCr peaked 24 h after I/R, BUN after 48 h, respectively, in the placebo treated I/R group. At all investigated time points after I/R sCr and BUN was higher in the I/R + canagliflozin group as compared to placebo treated rats, whereas the empagliflozin group did not differ from the placebo group. I/R led to tubular dilatation and necrosis. Empagliflozin was able to reduce that finding whereas canagliflozin had no effect. Treatment with empagliflozin also resulted in a significant reduction in an improved inflammatory score (p = 0.006). Renal expression of kidney injury molecule-1 (KIM-1) increased after I/R and empagliflozin but not canagliflozin significantly alleviated KIM-1 expression. I/R reduced urinary miR-26a excretion. Empagliflozin but not canagliflozin was able to restore normal levels of urinary miR-26a. This study in an AKI model confirmed safety data in the EMPA-REG OUTCOME trial suggesting that empagliflozin might reduce AKI risk. The empagliflozin effects on KIM-1 and miR-26a might indicate beneficial regulation of inflammation. These data should stimulate clinical studies with AKI risk as primary endpoint.

Identifiants

DOI: 10.1016/j.biopha.2022.113357 PMID: 35792391
pubmed: 35792391
pii: S0753-3322(22)00746-6
doi: 10.1016/j.biopha.2022.113357
pii:
doi:

Substances chimiques

Benzhydryl Compounds 0
Canagliflozin 0SAC974Z85
MicroRNAs 0
Sodium-Glucose Transporter 2 Inhibitors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113357

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement B.K.K. reports lecture fees and/or advisory board memberships and/or study participation from Astellas, Bayer, Boehringer Ingelheim, Chiesi, Riepharm, Pfizer, Sanofi, Servier, and Vifor Pharma, all outside the submitted work. D.D and T.K. are research employees of Boehringer Ingelheim.

Auteurs

Chang Chu (C)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; The First Clinical Medical College of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Denis Delić (D)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorferstr. 65, 88397 Biberach, Germany.

Jana Alber (J)

University of Hohenheim, Department of Physiology, Stuttgart, Germany.

Martina Feger (M)

University of Hohenheim, Department of Physiology, Stuttgart, Germany.

Yingquan Xiong (Y)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany.

Ting Luo (T)

The First Clinical Medical College of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, China; Nephrology Division, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Ahmed A Hasan (AA)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Egypt.

Shufei Zeng (S)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany.

Mohamed M S Gaballa (MMS)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Faculty of Veterinary Medicine, Benha University, Toukh, Egypt.

Xin Chen (X)

Department of Nephrology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; The First Clinical Medical College of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Lianghong Yin (L)

The First Clinical Medical College of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: 13725251458@126.com.

Thomas Klein (T)

Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach, Germany.

Saban Elitok (S)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Klinikum Ernst von Bergmann gGmbH, Potsdam, Germany.

Bernhard K Krämer (BK)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; European Center for Angioscience, Medical Faculty Mannheim, University of Heidelberg, Germany.

Michael Föller (M)

University of Hohenheim, Department of Physiology, Stuttgart, Germany.

Berthold Hocher (B)

Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Germany; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China; IMD Institut für Medizinische Diagnostik Berlin-Potsdam GbR, Berlin, Germany. Electronic address: berthold.hocher@medma.uni-heidelberg.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › Insuffisance rénale › Atteinte rénale aigüe › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Composés benzhydryliques › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides › Canagliflozine › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Maladies cardiovasculaires › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Ischémie › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Techniques d'investigation › Perfusion › Reperfusion › Head-to-head comparison of two SGLT-2...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs du cotransporteur sodium-glucose de type 2 › Head-to-head comparison of two SGLT-2...