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Abstract: SA-PO1000

SGLT2 Inhibitors Reduce Urinary Mitochondrial DNA Copy Number in Both Diabetic and Non-Diabetic CKD Patients

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Lee, Haekyung, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
  • Cho, Junghyun, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
  • Chung, Eui Suk, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
  • Kim, Hyoungnae, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
  • Jeon, Jin seok, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
  • Kwon, Soon hyo, Soonchunhyang University Hospital, Yongsan-gu, Seoul , Korea (the Republic of)
Background

Sodium–glucose co-transporter 2 (SGLT2) inhibitors improve renal and cardiovascular outcomes in patients with chronic kidney disease (CKD) regardless of the presence of type 2 diabetes mellitus (T2DM). In this work, we aimed to investigate whether SGLT2 inhibitors improve mitochondrial dysfunction in patients with T2DM or CKD.

Methods

We prospectively recruited SGLT2 inhibitor naïve patients with T2DM (n = 16), non-diabetic CKD (n = 16) and normal control (n= 22). Copy numbers of urinary mitochondrial DNA (mtDNA) in the form of mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured at baseline and after 3 months of treatment with SGLT2 inhibitors (empagliflozin in the T2DM group and dapagliflozin in the non-diabetic CKD group).

Results

Immunoglobulin A nephropathy was the most common underlying kidney disease (50%) in the non-diabetic CKD group. Estimated glomerular filtration rate was higher and albuminuria was lower in the T2DM group than in the non-diabetic CKD group (both p <0.001). Baseline urinary mtDNA levels were significantly higher in either T2DM or non-diabetic CKD group than in healthy controls (p <0.001 for mtND-1 and mtCOX-3, respectively), with mtDNA copy numbers comparable between the diabetic and non-diabetic CKD groups. SGLT2 inhibitors reduced urinary copy numbers of mtND-1 and mtCOX-3 in both the T2DM (p <0.001 for mtND-1 and mtCOX-3, respectively) and non-diabetic CKD groups (p <0.05 for mtND-1 and mtCOX-3, respectively) (Figure 1). The amount of reduction in urinary mtDNA copy number did not differ according to each SGLT2 inhibitor.

Conclusion

SGLT2 inhibitors reduce the elevated urinary mtND-1 and mtCOX-3 copy numbers in patients with T2DM or non-diabetic CKD, suggesting that SGLT2 inhibitors improve mitochondrial injury regardless of the presence of T2DM.

Figure 1. Change in urinary mitochondrial DNA copy numbers after sodium–glucose co-transporter 2 inhibitor treatment. (A) mtND-1, (B) mtCOX-3