Abstract: FR-PO642

The Study of Mechanisms of SGLT2 Inhibitors for Renoprotection in Human Diabetic Kidney Disease

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Author

  • Sato, Saeko, Saitama Medical center, Saitama Medical University, Kawagoe, Japan
Background

SGLT2 inhibitor (SGLT2i) has been reported to suppress not only glomerular hyperfiltration, but also have direct action on renal proximal tubule cells in vitro. There have been no reports on detailed investigations of its mechanism in humans, and there are many discussions about that. Therefore, we explore the effect of verious SGLT2i on kidney function and kidney injury in patients with diabetic kidney disease (DKD).

Methods

In patients with type 2 diabetes (T2DM) with DKD, the usual dose of SGLT2 inhibitor (Iplagliflozin 50mg or Canagliflozin 100mg or Dapagliflozin 5mg or Luceogliflozin 2.5mg or Tofogliflozin 20mg or Empagliflozin 10 mg) (when the effect was insufficient, it could be increased to the maximum dose), we compared and examined the several items before administration and one month after, 12 months after.

Results

73 cases was subjected. Administration of SGLT2i significantly reduced HbA1c and mean blood pressure in the examination room also decreased significantly after one month and 12 month (data not shown).
In renal function, estimate glomerular filtration rate (eGFRcreat) decreased significantly after one month, but improved after 12 months (61.3 ± 21.8 → 59.7 ± 22.5 (p = 0.0201) → 61.4 ± 23.7 mg/gCr). The urine albumin-to-creatinine ratio (u-ACR) decreased significantly both after one month and 12 months (560.2 ± 882.7 → 323.4 ± 553.4 (p = 0.0082) → 281.5 ± 430.2 mg/gCr (p = 0.0054)).
In inflammation or oxidative stress biomarkers, malondialdehyde modified LDL (MDA-LDL) was significantly decreased after one month and 12 months (133.4 ± 39.5 → 109 ± 28.2 U / L (p = 0.0141) after 12 months). Urinary monocyte chemoattractant protein 1 (MCP-1) did not change after one month, but it decreased significantly after 12 months (2.49 ± 1.75 → 1.27 ± 1.39 pg/gCr (p = 0.0169)). Urinary liver-type fatty-acid-binding protein (L-FABP) also did not change after one month, but it decreased significantly in 12 months (11.4 ± 21.7 → 8.0 ± 16.8 μg/gCr (p = 0.0004)).
There was no correlation between the rate of change in HbA1c or the rate of change in blood pressure and the rates of change in eGFR, u-ACR, MDA-LDL, u-MCP-1 and u-L-FABP.

Conclusion

Renoprotection of SGLT2i for DKD in T2DM is considered to be the main mechanism of improvement of glomerular hypertension at early stage, but direct suppression of inflammation and oxidative stress acts in the long term.