Abstract: FR-PO983
Dapagliflozin Suppresses Urinary Biomarkers of Kidney Damage Regardless of Proteinuric Levels in CKD
Session Information
- CKD Interventions: Trials and Quality Improvement
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Kim, Soyeon, Soonchunhyang University Hospital, Seoul, Korea (the Republic of)
- Chu, Seung Hye, 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)
Background
Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduce the risk of chronic kidney disease (CKD) progression in individuals with or without diabetes mellitus (DM). However, the beneficial effect of SGL2i on CKD patients with low levels of proteinuria has not been established. The objective of this study was to compare the effect of dapagliflozin on biomarkers of kidney injury in CKD patients stratified by albuminuria level.
Methods
We prospectively enrolled healthy volunteers (HVs) (n=20) and CKD patients (n=43) with or without DM. The CKD group received dapagliflozin (10mg). Urine and serum samples were collected before treatment and 3 and 6 months after administration of dapagliflozin. We measured kidney injury molecule-1 (KIM-1), interleukin-1β (IL-1β) and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND1) copy number in the urine.
Results
Age did not differ between HV and CKD patients (52.05 ± 8.13 vs 53.90 ± 14.96 years, p=0.774). The estimated glomerular filtration rate (eGFR) level of CKD patients was lower than that of HV (62.55 ± 24.22 vs 94.95 ± 11.21 mL/min, p < 0.001). Among the CKD patients, 11 % (n=5) had diabetes. The median urinary albumin/creatinine ratio (uACR) in CKD patients was 339.80 mg/g (IQR 80.0-647.0 mg/g). Kidney injury markers were significantly elevated in the CKD patients compared to the HVs. Dapagliflozin reduced urinary KIM-1, IL-1 β and mtND-1 in CKD at 6 months after treatment (p < 0.001, p < 0.001 and p = 0.021, respectively). Futhermore, when CKD patients were divided into two groups according to uACR level (< 300 mg/g, ≥ 300 mg/g), dapagliflozin decreased urinary KIM-1 and IL-1β at 3 months after treatment in the high albuminuria group (n=22) (p=0.034 and p=0.047, respectively). In the low albuminuria group (n=20), uKIM-1 and IL-1β decreased after 6 months of dapagliflozin treatment (p=0.004 and p=0.0021). However, dapagliflozin did not change uACR and eGFR during the study period.
Conclusion
CKD patients with high albuminuria showed an earlier response to dapagliflozin compared to those with low albuminuria. Nevertheless, dapagliflozin demonstrated a reduction in urinary kidney injury biomarkers in CKD patients regardless of proteinuria levels. These findings suggest that SGLT2i may attenuate the progression of low proteinuric CKD.
Funding
- Government Support – Non-U.S.