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Kidney Week

Abstract: TH-OR55

Effects of Canagliflozin on Renal Oxygenation Evaluated Using Blood Oxygenation Level-Dependent MRI in Patients with Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Mori, Katsuhito, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Inoue, Tsutomu, Saitama Medical University, Saitama, Japan
  • Machiba, Yuri, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Nakatani, Shinya, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Uedono, Hideki, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Ishikawa, Masahiro, Saitama Medical University, Saitama, Japan
  • Taniuchi, Satsuki, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Yamamoto, Akira, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Kobayashi, Naoki, Saitama Medical University, Saitama, Japan
  • Kozawa, Eito, Saitama Medical University, Saitama, Japan
  • Shimono, Taro, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Miki, Yukio, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
  • Okada, Hirokazu, Saitama Medical University, Saitama, Japan
  • Emoto, Masanori, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
Background

Results obtained in recent clinical trials suggest that SGLT2 inhibitors have protective effects against diabetic and chronic kidney disease, though the precise mechanisms remain largely unknown. Since the kidneys are susceptible to hypoxic damage, we hypothesized that use of an SGLT2 inhibitor improves renal oxygenation.

Methods

The effects of canagliflozin on renal oxygenation in patients with type 2 diabetes (T2D) were examined using blood oxygenation level-dependent (BOLD) MRI. Based on a method previously reported, T2* maps were generated, then primary analysis of cortical T2* values was performed using the 12-layer concentric objects (TLCO) method, while cortical oxygenation was also evaluated based on region of interest (ROI) method. The primary endpoints were change in T2* value from before (Day 0) to after the initial treatment (Day 1, about two hours after initial single dose) and also after five consecutive canagliflozin treatments (Day 5).

Results

Fourteen patients with T2D were enrolled, with median age 65.5 (interquartile range 59.0-72.0) years, body mass index 24.2 (22.3-26.7) kg/m2, HbA1c 7.1% (6.9-7.7%), estimated glomerular filtration rate 59.2 (46.9-76.8) mL/min/1.73 m2, and urinary albumin creatine ratio 20.5 (5.7-468.7) mg/gCr. Results with the TLCO method showed that canagliflozin treatment did not cause a significant change in T2* (mean and 95% confidential interval) from Day 0 [54.1 (51.4-56.9)] to Day 1 [55.2 (52.5-58.0)] (p=0.336) and also to Day 5 [53.4 (50.7-56.2)] (p=0.519). On the other hand, the T2* value was significantly increased from 52.8 (50.6-55.0) to 54.5 (52.3-56.9) (p=0.031) on Day 1, while no significant change from Day 0 to Day 5 [53.7 (51.5-56.0) (p=0.241)] was found with use of the ROI method.

Conclusion

The present findings indicate that canagliflozin administration may improve renal cortical oxygenation in patients with T2D.

Funding

  • Commercial Support – Mitsubishi Tanabe Pharma Corporation