Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease

Sakai, Yukinao; Otsuka, Tomoyuki; Ohno, Dai; Murasawa, Tsuneo; Sato, Naoki; Tsuruoka, Shuichi

doi:10.3109/0886022x.2013.844622

Cited by 37 publications

(30 citation statements)

References 20 publications

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“…Thus, renal function should be regularly monitored during drug treatment for ensuring safety. No serious adverse reaction occurred during the study, which is similar to the finding in previous study using febuxostat in severe CKD patients (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). The results indicate the safety of febuxostat use in CKD patients.…”

Section: Safetysupporting

confidence: 79%

“…However, previous information on the efficacy and safety of febuxostat use in CKD patients above stage 3 is limited. Several studies explored the efficacy and safety of using febuxostat for treating patients undergoing advanced CKD treatment (Table 5) (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). However, because of the limited number of patients included in this study and lower dosages used, further research is required for verifying the results.…”

Section: Discussionmentioning

confidence: 96%

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Febuxostat in patients with hyperuricemia and severe chronic kidney disease

Yang¹

2018

Afr. J. Pharm. Pharmacol.

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Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR).Its pharmacokinetics is not dependent on renal clearance, and it may be advantageous in patients with chronic kidney disease (CKD). Although febuxostat is effective in patients with mild-to-moderate CKD, its efficacy and safety in patients with severe CKD remain unclear. This retrospective study included patients with an estimated glomerular filtration rate (eGFR) of < 30 ml/min/1.73 m 2 and hyperuricemia, who received febuxostat. The study was performed at Kaohsiung Medical University Hospital between January, 2015 and December, 2015. Changes were observed in the serum uric acid level, rate of achieving the target uric acid level (<6.0 mg/dL), changes in the eGFR, treatment dosage, and adverse events. 217 patients (65.9 ± 15.1 yrs, 145 males and 72 females) with severe CKD and hyperuricemia were included. Febuxostat significantly lowered the serum uric acid level (9.4 ± 1.9 at baseline and 5.6 ± 1.9 ml/min after treatment, P < 0.001). The serum uric acid level was <6 mg/dl in 126 patients (58.1%). There were no significant changes in eGFR (17.6 ± 7.4 at baseline and 17.8 ± 8.9 ml/min after treatment, P = 0.642) or indices of liver dysfunction. Adverse events were found in 5 patients, all adverse events improved after discontinuing febuxostat. This study demonstrated that febuxostat is efficacious and well tolerated in severe CKD patients with hyperuricemia, although renal function monitoring may be needed.

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Section: Safetysupporting

confidence: 79%

Section: Discussionmentioning

confidence: 96%

Febuxostat in patients with hyperuricemia and severe chronic kidney disease

Yang¹

2018

Afr. J. Pharm. Pharmacol.

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“…Several studies reported a beneficial effect of UA lowering on CKD progression and UA has been proposed as a promising target of therapy in CKD patients. [37][38][39][40][41][42][43] Recently, Omori et al 37 reported that in animal models with obstructive nephropathy, febuxostat inhibited renal interstitial inflammation and fibrosis suggesting a therapeutic value in slowing CKD progression. In accordance, Sakai et al 42 reported that febuxostat by lowering UA levels in CKD patients may suppress the progression of CKD.…”

Section: Introductionmentioning

confidence: 99%

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

et al. 2014

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The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

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“…Another study also reported the usefulness of febuxostat in elderly patients with renal impairment [13] . Several studies have suggested that sustained urate-lowering therapy with febuxostat may impede renal decline in patients with gout [14,15] . However, the administration of febuxostat to patients with severe renal dysfunction (CCr <30 ml/min) or to those undergoing maintenance hemodialysis (HD) has not been examined in sufficient detail and is information that is clinically desired [16] .…”

Section: Population Pharmacokinetics and Therapeutic Efficacy Of Febumentioning

confidence: 99%

Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment

Hira

Chisaki²,

Noda³

et al. 2015

Pharmacology

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The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m², including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment.

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Febuxostat for treating allopurinol-resistant hyperuricemia in patients with chronic kidney disease

Cited by 37 publications

References 20 publications

Febuxostat in patients with hyperuricemia and severe chronic kidney disease

Febuxostat in patients with hyperuricemia and severe chronic kidney disease

Hyperuricemia and chronic kidney disease: an enigma yet to be solved

Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment

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