Abstract: FR-PO179
Clarification of the Mechanism of Acute GFR Change by SGLT2 Inhibition with In Vivo Imaging Technique
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
- Wada, Yoshihisa, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Kidokoro, Kengo, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Kondo, Megumi, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Tokuyama, Atsuyuki, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Kadoya, Hiroyuki, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Nagasu, Hajime, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Satoh, Minoru, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Sasaki, Tamaki, Kawasaki Madical School, Kurashiki, Okayama, Japan
- Kashihara, Naoki, Kawasaki Madical School, Kurashiki, Okayama, Japan
Background
SGLT2 inhibition (SGLT2i) exerted the effects to lower the risk of kidney failure in patients with type 2 diabetic kidney disease (DKD). Improvement of glomerular hyperfiltration via tubuloglomerular feedback (TGF) has been considered to be involved in this mechanism. We have successfully developed the novel method to measure single nephron GFR (SNGFR) in mice using multiphoton laser microscopy (MPM). We demonstrated that adenosine/adenosine 1a receptor (A1aR) pathway plays a pivotal role in the TGF mechanism in type 1 diabetic model, Akita mice (Circulation 2019). The purpose of this study is to clarify the acute effects of SGLT2i on glomerular hemodynamic in type 2 diabetic rat.
Methods
Zucker lean (ZL) rats and zucker diabetic fatty (ZDF) rats were used. Both rats were divided to the following groups; luseogliflozin (10mg/kg, gavage) group, luseogliflozin + adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1mg/kg) group, and insulin group. SNGFR was measured after four weeks of treatment. For the acute phase study, catheter was inserted into the ureter to collect urine. Serial urine-collections of urine were performed every 30 minutes after administration of luseogliflozin. Urinary excretions of glucose, sodium, and adenosine were measured. At the same time points, SNGFR was measured to evaluate the correlation between urinary excretions of these parameters and GFR change.
Results
SNGFR in the untreated ZDF group was significantly higher than in the ZL group. Luseogliflozin treatment increased urinary sodium and glucose excretion and reduced serum glucose level in the ZDF group. SNGFR significantly declined after 30 minutes and became stabilized until 90 minutes after administration, with inverse relationship to urinary sodium. The A1aR-antagonist group showed similar urinary excretion pattern, but initial decline of SNGFR was not observed.
Conclusion
Adenosine/ A1aR pathways play an important role in the regulation of GFR and is involved in the acute decline of GFR by SGLT2i treatment.