Abstract: FR-PO1184
Renoprotective Effect of 5-Aminolevulinic Acid in Adenine-Induced CKD via Protective Functions on Mitochondria
Session Information
- CKD: Mechanisms, AKI, and Beyond - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Hori, Koji, The University of Tokyo Graduate School of Agricultural and Life Sciences, Bunkyo, Tokyo, Japan
- Tomita, Kenji, The University of Tokyo Graduate School of Agricultural and Life Sciences, Bunkyo, Tokyo, Japan
- Sato, Emiko, Tohoku University Graduate School of Pharmaceutical Sciences, Miyagi, Sendai, Japan
- Maeda, Shingo, The University of Tokyo Graduate School of Agricultural and Life Sciences, Bunkyo, Tokyo, Japan
- Momoi, Yasuyuki, The University of Tokyo Graduate School of Agricultural and Life Sciences, Bunkyo, Tokyo, Japan
- Yonezawa, Tomohiro, The University of Tokyo Graduate School of Agricultural and Life Sciences, Bunkyo, Tokyo, Japan
Background
The number of patients with chronic kidney disease (CKD) is increasing worldwide, and CKD can progress to end-stage renal disease (ESRD), leading to death. Oxidative stress is known to be involved in the onset and progression of CKD. In this study, we evaluated the efficacy of the antioxidant 5-aminolevulinic acid(5-ALA) against CKD with using adenine-induced CKD model mice.
Methods
Male 8-week old C57BL/6 mice were assigned and randomly divided into 4 groups: control group, 5-ALA group, adenine group (CKD group), and adenine+5-ALA group (treatment group). Adenine groups were fed a diet containing 0.2 % adenine, while the others were fed a normal diet. For prophylactic treatment, the mice were supplied with tap water as control or the water containing 5-ALA phosphate and sodium ferrous citrate (SFC) ad libitum (1.5 ml/ml as 5-ALA, overall molar ratio was 5-ALA:SFC = 1:0.05). After 6 weeks, blood and urine samples were collected and the mice were sacrificed and kidney tissues were sampled. The kidney index was calculated by dividing the kidney weight by the body weight. Transdermal GFR (tGFR), urine albumin/creatinine ratio (uACR), BUN, creatinine, and oxidative stress markers (8-OHdG, MDA) were evaluated. Renal pathology including HE and masson trichrome staining, F4/80 staining (marker of macrophages), COX staining (marker of mitochondrial dysfunction) and ultra-structural pathology using TEM in the kidney were analyzed. Statistical analysis was performed on the data obtained for each parameter.
Results
CKD group have atrophy in kidney significantly and shows significant decrease of kidney function on tGFR, uACR, BUN, and creatinine compared to the control group. Administration of 5-ALA ameliorate kidney atrophy partially and improve kidney functions significantly. In treatment group, plasma concentration of 8-OHdG decrease and tissue MDA decrease partially compare to CKD group. In pathology, CKD group mice have severe tubulointerstitial injury, fibrosis, infiltration of macrophages, mitochondrial hypofunction and disruption of mitochondrial structure. Whereas treatment of 5-ALA attenuates these changes.
Conclusion
Prophylactic treatment of 5-ALA alleviates adenine-induced CKD from both functional and structural aspects. It suggests the potential for 5-ALA to be used in the treatment of CKD.