Changeover Trial of Febuxostat and Topiroxostat for Hyperuricemia with Cardiovascular Disease: Sub-Analysis for Chronic Kidney Disease (TROFEO CKD Trial)

Sezai, Akira; Unosawa, Satoshi; Taoka, Makoto; Osaka, Shunji; Sekino, Hisakuni; Tanaka, Masashi

doi:10.5761/atcs.oa.19-00162

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…This suggests that while both medications effectively lowered SUA levels in hyperuricemia patients, they did so to a comparable extent, without a discernible difference between the two treatment groups. Similarly, according to the TROFEO study [5] there was no significant difference in serum uric acid levels between the Topiroxostat and febuxostat groups either before or after treatment, but they also concluded reduction of serum uric acid was more rapid with febuxostat than topiroxostat which was not present in our study.…”

Section: Discussionsupporting

confidence: 63%

“…Additionally, Kario K et al in 2021 found that while urinary albumin-creatinine ratio (UACR) significantly decreased from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), it did not significantly change with febuxostat (-8.8%; p = 0.362) [14] . However, findings from the TROFEO CKD trial study suggested that febuxostat demonstrated more potent renal protective effects than topiroxostat [15] . The eGFR analysis from Table 4 indicates a statistically significant improvement in eGFR values within the Topiroxostat group over the 12-week period, with a mean improvement of 0.6375 mL/min/1.73 m 2 and a p-value of 0.00034.…”

Section: Discussionmentioning

confidence: 99%

“…Kazuomi Kario in his study on Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia gave febuxostat and topiroxostat at dosages of 10-60mg/dl and 40-160mg/dl respectively [4] . Similar dosages has been used by Akira Sezai in the TROFEO study [5] .…”

Section: Interventionsmentioning

confidence: 90%

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Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

Senthil,

Khanna

2024

Int. J. Orthop. Sci.

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Hyperuricemia is a metabolic condition associated with various health complications, including gout, kidney disease, and cardiovascular events. Topiroxostat and febuxostat are two commonly prescribed xanthine oxidase inhibitors for managing hyperuricemia, yet there is a paucity of direct comparative studies evaluating their efficacy and safety profiles. To address this gap, we conducted a prospective, randomized, open-label, parallel-group trial involving 50 patients diagnosed with hyperuricemia. Patients were randomly assigned to receive either topiroxostat or febuxostat for a duration of 12 weeks. Primary outcome measures included changes in serum uric acid (SUA) levels, while secondary outcomes encompassed renal function parameters and incidence of adverse events. Our findings indicate that both topiroxostat and febuxostat effectively reduced SUA levels over the treatment period, with no significant difference observed between the two groups. However, topiroxostat demonstrated a more significant reduction in serum creatinine levels, urinary albumin excretion, and improvement in estimated glomerular filtration rate (eGFR) compared to febuxostat. Safety profiles were favorable for both medications, with no serious adverse events reported. These results suggest that while both topiroxostat and febuxostat are effective in lowering SUA levels, topiroxostat may offer additional renal protective benefits. Further comparative studies are warranted to elucidate the clinical implications and optimal use of these medications in hyperuricemia management.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

Senthil,

Khanna

2024

Int. J. Orthop. Sci.

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“…For example, related results have shown that topiroxostat ameliorates kidney injury in puromycin aminonucleoside nephrosis rats by reducing oxidative stress and the UA concentration [ 135 , 136 ]. However, febuxostat had stronger renoprotective and antioxidant effects than topiroxostat in patients with hyperuricemia and chronic kidney disease (CKD) [ 137 ].…”

Section: Xanthine Oxidase Inhibition Studiesmentioning

confidence: 99%

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

Liu

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.

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“…Moreover, febuxostat was more effective and faster than allopurinol in achieving the serum uric acid target in patients with gout [36]. Similarly, febuxostat has an advantage over topiroxostat in cardiorenal protection in hyperuricemic patients with cardiovascular disease [37,38]. Recently, there have been only two reports on the treatment of SI-AKI with febuxostat showing that febuxostat improves the prognosis of SI-AKI animals through antioxidant stress and anti-inflammation [20,21].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Xanthine oxidase (XO) utilizes molecular oxygen as a substrate to convert purine substrates into uric acid, superoxide, and hydrogen peroxide, which is one of the main enzyme pathways to produce reactive oxygen species (ROS) during septic inflammation and oxidative stress. However, it is not clear whether XO inhibition can improve sepsis-induced renal hypoxia in sepsis-induced acute kidney injury (SI-AKI) mice. In this study, pretreatment with febuxostat, an XO-specific inhibitor, or kidney knockdown of XO by shRNA in vivo significantly improved the prognosis of SI-AKI, not only by reducing the levels of blood urea nitrogen, serum creatinine, tumor necrosis factor-α, interleukin-6, and interleukin-1β in peripheral blood but also by improving histological damage and apoptosis, reducing the production of ROS, and infiltrating neutrophils and macrophages in the kidney. More importantly, we found that pharmacological and genetic inhibition of XO significantly improved renal hypoxia in SI-AKI mice by a hypoxia probe via fluorescence staining. This effect was further confirmed by the decrease in hypoxia-inducible factor-1α expression in the kidneys of mice with pharmacological and genetic inhibition of XO. In vitro, the change in XO activity induced by lipopolysaccharide was related to the change in hypoxia in HK-2 cells. Febuxostat and XO siRNA significantly relieved the hypoxia of HK-2 cells cultured in 2% oxygen and reversed the decrease in cell viability induced by lipopolysaccharide. Our results provide novel insights into the nephroprotection of XO inhibition in SI-AKI, improving cell hypoxia by inhibiting XO activity and reducing apoptosis, inflammation, and oxidative stress.

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Changeover Trial of Febuxostat and Topiroxostat for Hyperuricemia with Cardiovascular Disease: Sub-Analysis for Chronic Kidney Disease (TROFEO CKD Trial)

Cited by 8 publications

References 21 publications

Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

Navigating the choice between topiroxostat and febuxostat for hyperuricemia management: A prospective comparative study

The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

Inhibition of Xanthine Oxidase Protects against Sepsis-Induced Acute Kidney Injury by Ameliorating Renal Hypoxia

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