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

Front Endocrinol (Lausanne). 2024 Aug 30:15:1451671. doi: 10.3389/fendo.2024.1451671. eCollection 2024.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.

Keywords: BOLD MRI; GFR; SGLT2 inhibitor; kidney disease; kidney oxygenation; type 2 diabetes.

MeSH terms

  • Aged
  • Canagliflozin* / therapeutic use
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney* / diagnostic imaging
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Oxygen* / blood
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Canagliflozin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Oxygen
  • Hypoglycemic Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Mitsubishi Tanabe Pharma Corporation. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.