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Abstract: TH-PO1172

SGLT2 Inhibitor Alters Circulating Mitokine Levels in Patients with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Jeong, Seunghwan, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
  • Noh, Hyunjin, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
  • Kwon, Soon hyo, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
  • Lee, Haekyung, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
Background

Mitokines are released in response to mitochondrial stress and the mitochondrial unfolded protein response. They play a crucial role in inter-organ communication. Sodium–glucose co-transporter 2 (SGLT2) inhibitors mitigate mitochondrial dysfunction. In this study, we aimed to investigate changes in mitokine levels in patients with chronic kidney disease (CKD) and the effects of SGLT2 inhibitor treatment.

Methods

We prospectively recruited SGLT2 inhibitor-naïve patients with CKD (n = 68; 22.1 % with diabetes) and healthy controls (n= 35). Circulating mitokine levels—fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and humanin—were measured using ELISA. In patients with CKD, mitokine levels were reassessed at 3 and 6 months following SGLT2 inhibitor treatment.

Results

Compared to healthy controls, levels of MOTS-c, FGF21, and humanin were increased, whereas GDF15 levels were decreased in CKD patients (Figure 1). When patients with CKD were stratified into two groups based on their respective baseline mitokine levels, MOTS-c levels decreased 6 months after SGLT2 inhibitor treatment in the high baseline group (P = 0.014). In the low GDF15 group, GDF15 levels increased at 3 months and remained elevated at 6 months after SGLT2 inhibitor treatment. In contrast, in the high GDF15 group, the levels decreased at 3 months and remained decreased at 6 months. FGF21 levels decreased at 6 months compared to 3 months in both the low and high groups. Humanin levels increased at 3 months and remained elevated at 6 months, but this effect was observed only in the low group.

Conclusion

CKD is associated with dysregulated circulating mitokine levels. SGLT2 inhibitor treatment resulted in dynamic changes in mitokine levels, suggesting that SGLT2 inhibitors could attenuate mitochondrial damage in patients with CKD.

Digital Object Identifier (DOI)