Safety and Efficacy of Dotinurad on Uric Acid in Patients With Chronic Kidney Disease With Estimated Glomerular Filtration Rate Below 25 ML/Min/1.73 M²

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2024 May 2

PMID 38694413

Authors

Akira Mima

Hidemasa Gotoda

Shinji Lee

Affiliations

Soon will be listed here.

Abstract

Introduction Dotinurad is being developed as a selective uric acid reabsorption inhibitor. However, its effect on lowering serum uric acid (UA) levels in chronic kidney disease (CKD) patients with severe renal dysfunction is unknown. Therefore, the purpose of this study was to determine the effect of dotinurad on renal function in CKD patients with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73 m. Methods Seven patients with CKD who received dotinurad 0.5 mg to 4 mg per day were studied retrospectively. Changes in UA, eGFR, and urine protein-to-creatinine ratio (UPCR) were analyzed. The observation period was 10.9±2.1 months. Results Serum UA levels were decreased and maintained with dotinurad administration. Nevertheless, there were no improvements noted in renal function. Additionally, no serious adverse effects were identified in any of the patients throughout the observation period. Conclusion Although the sample size in this study was small, our findings demonstrate the efficacy of dotinurad in individuals with advanced CKD who have an eGFR lower than 25 mL/min/1.73 m.

References

Mima A, Murakami A, Lee R, Lee S . Predictive significance of glomerular insulin receptor substrate-1 in patients with diabetic kidney disease. Metabol Open. 2023; 18:100240. PMC: 10070893. DOI: 10.1016/j.metop.2023.100240. View

Mima A . Prediction of decreased estimated glomerular filtration rate using liver fibrosis markers: a renal biopsy-based study. Sci Rep. 2022; 12(1):17630. PMC: 9587235. DOI: 10.1038/s41598-022-22636-9. View

Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y . Modification of the Modification of Diet in Renal Disease (MDRD) Study equation for Japan. Am J Kidney Dis. 2007; 50(6):927-37. DOI: 10.1053/j.ajkd.2007.09.004. View

FitzGerald J, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles A . 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020; 72(6):744-760. PMC: 10563586. DOI: 10.1002/acr.24180. View

Mima A, Matsubara T, Arai H, Abe H, Nagai K, Kanamori H . Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy. Lab Invest. 2006; 86(9):927-39. DOI: 10.1038/labinvest.3700445. View

Mima A . Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease. J Diabetes Complications. 2018; 32(7):720-725. DOI: 10.1016/j.jdiacomp.2018.04.011. View

Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha S . Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002; 417(6887):447-52. DOI: 10.1038/nature742. View

Mima A . Safety and Efficacy of Imeglimin for Type 2 Diabetes in Patients Undergoing Dialysis. In Vivo. 2023; 37(3):1334-1338. PMC: 10188007. DOI: 10.21873/invivo.13214. View

Kang D, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M . A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002; 13(12):2888-97. DOI: 10.1097/01.asn.0000034910.58454.fd. View

10.

Hung S, Kuo K, Wu C, Tarng D . Indoxyl Sulfate: A Novel Cardiovascular Risk Factor in Chronic Kidney Disease. J Am Heart Assoc. 2017; 6(2). PMC: 5523780. DOI: 10.1161/JAHA.116.005022. View

11.

Mima A, Kitada M, Geraldes P, Li Q, Matsumoto M, Mizutani K . Glomerular VEGF resistance induced by PKCδ/SHP-1 activation and contribution to diabetic nephropathy. FASEB J. 2012; 26(7):2963-74. PMC: 3382088. DOI: 10.1096/fj.11-202994. View

12.

Yamanaka H . Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids. 2011; 30(12):1018-29. DOI: 10.1080/15257770.2011.596496. View

13.

Hisatome I, Li P, Miake J, Taufiq F, Mahati E, Maharani N . Uric Acid as a Risk Factor for Chronic Kidney Disease and Cardiovascular Disease　- Japanese Guideline on the Management of Asymptomatic Hyperuricemia. Circ J. 2020; 85(2):130-138. DOI: 10.1253/circj.CJ-20-0406. View

14.

Mima A . A Narrative Review of Diabetic Kidney Disease: Previous and Current Evidence-Based Therapeutic Approaches. Adv Ther. 2022; 39(8):3488-3500. DOI: 10.1007/s12325-022-02223-0. View

15.

Mikuls T, Maclean C, Olivieri J, Patino F, Allison J, Farrar J . Quality of care indicators for gout management. Arthritis Rheum. 2004; 50(3):937-43. DOI: 10.1002/art.20102. View

16.

Mima A, Ohshiro Y, Kitada M, Matsumoto M, Geraldes P, Li C . Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int. 2011; 79(8):883-96. PMC: 3612886. DOI: 10.1038/ki.2010.526. View

17.

Drozdzik M, Czekawy I, Oswald S, Drozdzik A . Intestinal drug transporters in pathological states: an overview. Pharmacol Rep. 2020; 72(5):1173-1194. PMC: 7550293. DOI: 10.1007/s43440-020-00139-6. View

18.

Miyata H, Takada T, Toyoda Y, Matsuo H, Ichida K, Suzuki H . Identification of Febuxostat as a New Strong ABCG2 Inhibitor: Potential Applications and Risks in Clinical Situations. Front Pharmacol. 2017; 7:518. PMC: 5187494. DOI: 10.3389/fphar.2016.00518. View

19.

Hosoya T, Sano T, Sasaki T, Fushimi M, Ohashi T . Clinical efficacy and safety of dotinurad, a novel selective urate reabsorption inhibitor, in Japanese hyperuricemic patients with or without gout: randomized, multicenter, double-blind, placebo-controlled, parallel-group, confirmatory phase 2 study. Clin Exp Nephrol. 2019; 24(Suppl 1):53-61. PMC: 7066091. DOI: 10.1007/s10157-019-01818-2. View

20.

Mima A, Qi W, King G . Implications of treatment that target protective mechanisms against diabetic nephropathy. Semin Nephrol. 2012; 32(5):471-8. PMC: 3584697. DOI: 10.1016/j.semnephrol.2012.07.010. View