ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO187

Effect of Canagliflozin on Glomerular Hyperfiltration Evaluated by Transcutaneous GFR Monitor in Spontaneously Diabetic Torii Fatty Rats

Session Information

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.