A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease
Abstract
:1. Introduction
2. The Association of URAT1 and Other UA Transporters with Metabolic Syndrome
2.1. Metabolic Syndrome and Hyperuricemia
2.2. The Effect of Insulin Resistance on URAT1 Expression
2.3. The Effect of Insulin on UA Transport by Other Urate Transporters
2.4. The Effect of Inhibition of URAT1 on Metabolic Parameters in Humans
2.5. The Effect of Inhibition of URAT1 on Metabolic Parameters in Mice
2.6. The Effects of Other UA-Lowering Drugs on Metabolic Parameters
2.7. The Possible Mechanisms of an Improvement in Metabolic Parameters by Dotinurad
3. The Association of URAT1 and Other UA Transporters with CKD
3.1. CKD and Hyperuricemia
3.2. The Effect of CKD on Renal URAT1 Expression
3.3. The Effect of CKD on Other Urate Transporter Expressions
3.4. The Effect of IS on CKD
3.5. The Effect of Inhibition of URAT1 on CKD
3.6. The Effects of Other UA-Lowering Drugs on CKD
3.7. The Effects of Febuxostat and Dotinurad on Advanced CKD
UA-Lowering Drugs | XO Inhibitors | Uricosuric Drugs | ||||
---|---|---|---|---|---|---|
Allopurinol | Febuxostat | Topiroxostat | Benzbromarone | Probenecid | Dotinurad | |
Inhibition of UA Transporters | ABCG2 | ABCG2 | ABCG2 | ABCG2 | URAT1 | |
URAT1 | URAT1 | |||||
GLUT9 | GLUT9 | |||||
OAT1 | OAT1 | |||||
OAT3 | OAT3 | |||||
Albuminuria | No data | Improved [85,87,90] | Improved [92] | No data | No data | Improved [14,79] |
eGFR or serum creatinine | Improved [82,83] | Improved [85] | Not improved [93] and Improved [94] | No data | No data | Improved [14,79,80,81] |
eGFR in patients with CKD stage 4 and 5 | No data | Not improved [96,97] | No data | No data | No data | Improved [79,80,81] |
Proximal tubular impairment | No data | Improved [87] | Not improved [93] | No data | No data | No data |
Renal outcomes | Improved [84] | Improved [91] | No data | Improved [95] | No data | No data |
4. The Association of URAT1 and Other UA Transporters with the Development of CVD
4.1. The Association of URAT1 with Atherogenesis
4.2. The Association of Other UA Transporters with Atherogenesis
4.3. The Effect of Inhibition of URAT1 on Atherosclerosis
4.4. The Effects of Other UA-Lowering Drugs on Endothelial Function
4.5. The Effects of UA-Lowering Drugs on CVD
5. A Summary of Unfavorable Effects of the Inhibition of ABCG2, OAT1, and OAT3 on the Kidneys and Vascular Endothelial Cells in CKD Patients
6. A Summary of the Beneficial Effects of Dotinurad on the Kidneys and Atherosclerosis in CKD Patients
7. Possible Beneficial Effects of Dotinurad for Heart Failure (HF)
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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UA-Lowering Drugs | XO Inhibitors | Uricosuric Drugs | ||||
---|---|---|---|---|---|---|
Allopurinol | Febuxostat | Topiroxostat | Benzbromarone | Probenecid | Dotinurad | |
Inhibition of UA Transporters | ABCG2 | ABCG2 | ABCG2 | ABCG2 | URAT1 | |
URAT1 | URAT1 | |||||
GLUT9 | GLUT9 | |||||
OAT1 | OAT1 | |||||
OAT3 | OAT3 | |||||
Body weight | Reduced | Reduced | Suppressed weight gain | Reduced | No data | Reduced |
(animal) [41] | (animal and human) [41,54] | (animal) [55] | (human) [54] | (animal and human) [14,33] | ||
Visceral fat | Reduced | Reduced | No change | Reduced | No data | Reduced |
(animal) [42,56] | (human) [54] | (animal) [55] | (human) [54] | (animal) [33] | ||
Blood pressure | Reduced | Reduced | No data | Reduced | Reduced [56] (human) | Reduced |
(animal and human) [41,56] | (animal and human) [41,54] | (human) [54] | (animal and human) [14,33] | |||
Glucose metabolism | Improved | Improved | No data | No change | No data | Improved |
(animal) [41] | (animal) [41] | (human) [54] | (animal and human) [14,33] | |||
Serum lipids | Improved | Improved | No data | Improved | No data | Improved |
(animal) [41] | (animal and human) [41,54] | (human) [54] | (animal and human) [14,33] | |||
Hepatic steatosis | Improved | Improved | No change | Improved | No data | Improved |
(animal) [42] | (human) [54] | (animal) [55] | (human) [54] | (animal) [33] |
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Yanai, H.; Adachi, H.; Hakoshima, M.; Iida, S.; Katsuyama, H. A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease. Cells 2024, 13, 450. https://doi.org/10.3390/cells13050450
Yanai H, Adachi H, Hakoshima M, Iida S, Katsuyama H. A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease. Cells. 2024; 13(5):450. https://doi.org/10.3390/cells13050450
Chicago/Turabian StyleYanai, Hidekatsu, Hiroki Adachi, Mariko Hakoshima, Sakura Iida, and Hisayuki Katsuyama. 2024. "A Possible Therapeutic Application of the Selective Inhibitor of Urate Transporter 1, Dotinurad, for Metabolic Syndrome, Chronic Kidney Disease, and Cardiovascular Disease" Cells 13, no. 5: 450. https://doi.org/10.3390/cells13050450