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Clin Pharmacol Ther ; 115(6): 1441-1449, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38451017

RÉSUMÉ

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) with low albuminuria levels have not been established. This study aimed to compare the effects of dapagliflozin on kidney injury biomarkers in patients with CKD stratified by albuminuria level. We prospectively enrolled healthy volunteers (HVs; n = 20) and patients with CKD (n = 54) with and without diabetes mellitus. Patients with CKD were divided into two age-matched and sex-matched subgroups according to urinary albumin-creatinine ratio (uACR) levels (<300 mg/g and ≥300 mg/g). The CKD group received dapagliflozin (10 mg/day). Urine samples were collected before treatment and after 3 and 6 months of dapagliflozin. Urinary kidney injury molecule-1 (KIM-1), interleukin-1ß (IL-1ß), and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND1) copy number were measured. The estimated glomerular filtration rate (eGFR) of patients with CKD was lower than that of HVs (P < 0.001). During the study period, eGFR decreased and uACR did not change in the CKD group. Kidney injury markers were significantly elevated in patients with CKD compared with those in HVs. Dapagliflozin reduced urinary KIM-1, IL-1ß, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM-1 and IL-1ß, patients with CKD decreased after 6 months of dapagliflozin treatment regardless of albuminuria level. Dapagliflozin reduced urinary kidney injury biomarkers in patients with CKD, regardless of albuminuria level. These findings suggest that SGLT2 inhibitors may also attenuate the progression of low albuminuric CKD.


Sujet(s)
Albuminurie , Composés benzhydryliques , Marqueurs biologiques , Débit de filtration glomérulaire , Glucosides , Insuffisance rénale chronique , Inhibiteurs du cotransporteur sodium-glucose de type 2 , Humains , Composés benzhydryliques/usage thérapeutique , Albuminurie/urine , Albuminurie/traitement médicamenteux , Mâle , Femelle , Glucosides/usage thérapeutique , Marqueurs biologiques/urine , Insuffisance rénale chronique/urine , Insuffisance rénale chronique/traitement médicamenteux , Insuffisance rénale chronique/physiopathologie , Adulte d'âge moyen , Inhibiteurs du cotransporteur sodium-glucose de type 2/usage thérapeutique , Études prospectives , Sujet âgé , Débit de filtration glomérulaire/effets des médicaments et des substances chimiques , Récepteur cellulaire-1 du virus de l'hépatite A/métabolisme , Adulte , Interleukine-1 bêta/urine , Études cas-témoins , Diabète de type 2/traitement médicamenteux , Diabète de type 2/urine , Diabète de type 2/complications
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