1. Dapagliflozin Reduces Urinary Kidney Injury Biomarkers in Chronic Kidney Disease Irrespective of Albuminuria Level.
- Author
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Cho J, Doo SW, Song N, Lee M, Lee H, Kim H, Jeon JS, Noh H, and Kwon SH
- Subjects
- Humans, Male, Female, Middle Aged, Prospective Studies, Aged, Hepatitis A Virus Cellular Receptor 1 metabolism, Adult, Interleukin-1beta urine, Case-Control Studies, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 urine, Diabetes Mellitus, Type 2 complications, Benzhydryl Compounds therapeutic use, Albuminuria urine, Albuminuria drug therapy, Glucosides therapeutic use, Biomarkers urine, Renal Insufficiency, Chronic urine, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic physiopathology, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Glomerular Filtration Rate drug effects
- Abstract
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-1β (IL-1β), 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-1β, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM-1 and IL-1β, 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., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2024
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