Effects of canagliflozin on kidney oxygenation evaluated using blood oxygenation level-dependent MRI in patients with type 2 diabetes

Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation. A single-arm study was conducted to investig...

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Published in:Frontiers in endocrinology (Lausanne) 2024-08, Vol.15, p.1451671
Main Authors: Mori, Katsuhito, Inoue, Tsutomu, Machiba, Yuri, Uedono, Hideki, Nakatani, Shinya, Ishikawa, Masahiro, Taniuchi, Satsuki, Katayama, Yutaka, Yamamoto, Akira, Kobayashi, Naoki, Kozawa, Eito, Shimono, Taro, Miki, Yukio, Okada, Hirokazu, Emoto, Masanori
Format: Article
Language:English
Subjects:
Aged
BOLD MRI
Canagliflozin - therapeutic use
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - drug therapy
Female
GFR
Humans
Hypoglycemic Agents - therapeutic use
Kidney - diagnostic imaging
Kidney - drug effects
Kidney - metabolism
kidney disease
kidney oxygenation
Magnetic Resonance Imaging - methods
Male
Middle Aged
Oxygen - blood
SGLT2 inhibitor
Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
type 2 diabetes
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Summary:Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation. A single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods. In the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI. Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2024.1451671