Abstract: FR-PO187
Effect of Canagliflozin on Glomerular Hyperfiltration Evaluated by Transcutaneous GFR Monitor in Spontaneously Diabetic Torii Fatty Rats
Session Information
- Diabetic Kidney Disease: Basic - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Kodama, Goh, Kurume University School of Medicine, Fukuoka, Japan
- Nakayama, Yosuke, Kurume University School of Medicine, Fukuoka, Japan
- Ito, Sakuya, Kurume University School of Medicine, Fukuoka, Japan
- Yokota, Yunosuke, Kurume University School of Medicine, Fukuoka, Japan
- Fukami, Kei, Kurume University School of Medicine, Fukuoka, Japan
Group or Team Name
- Division of Nephrology, Department of Medicine, Kurume University School of Medicine
Background
Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce glomerular hyperfiltration, thereby preventing the progression of diabetic kidney disease. However, since consecutive measurements of total nephron GFR in a same experimental model is not fully established, it is difficult to assess the precise effects of SGLT2 inhibitors on tubuloglomerular feedback (TGF). Transcutaneous GFR monitor (MediBeacon®) allows consecutive measurements by detecting fluorescence of FITC-sinistrin on the same animal, including multiple measurements with no sampling. Therefore, we assessed the effects of canagliflozin (CANA) on glomerular hemodynamic effects using transcutaneous GFR monitor in Spontaneously Diabetic Torii fatty rat (SDT-fatty rat), an obese type 2 diabetic model.
Methods
Eight week-SDT-fatty rats were given 100 mg/kg of CANA. Sprague Dawley (SD) rats were used as control. Fluorescence monitoring device was placed onto back of rats, and FITC-sinistrin was injected intravenously. After 2 hours, device was removed and half-life of sinistrin was measured, and then GFR was calculated. GFR could be measured one day before, 2 hours after, and 1 week after the treatment with CANA in a same rat. Adenosine production in response to increased sodium chloride reabsorption by CANA is evaluated by measuring urinary adenosine levels. SDT-fatty rats are treated with selective A1 adenosine receptor (A1aR) antagonist before administration of CANA.
Results
Serum glucose levels significantly increased in SDT-fatty rats (235.0mg/dL vs 133.8mg/dL). Baseline GFR in SDT-fatty rats was significantly higher than that in SD rats (23.7ml/min/kg, 15.3ml/min/kg, respectively). Treatment with CANA dramatically reduced diabetes-induced increased GFR at 2 hours after administration (17.3ml/min/kg) compared to baseline (p<0.01 vs baseline GFR). GFR at 1 week after administration with CANA in a same rat returned to baseline level without glucosuria (22.7ml/min/kg, p=0.49 vs baseline GFR). Urinary adenosine levels at 2 hours after administration with CANA and the effects of co-administration with A1aR antagonist on CANA-induced reduction of GFR will be evaluated.
Conclusion
SGLT2 inhibition plays a pivotal role in the regulation of GFR via TGF in SDT-fatty rats, which may contribute to renal protective effects reported in clinical trials.