Challenges Associated with the Management of Gouty Arthritis in Patients with Chronic Kidney Disease: A Systematic Review

Curiel, Rodolfo V.; Guzmán, Nicolás

doi:10.1016/j.semarthrit.2012.03.013

Cited by 49 publications

(65 citation statements)

References 99 publications

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“…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] . To the best of our knowledge, a population-based pharmacokinetic approach for febuxostat has not yet been reported and may provide a basis for the safe and effective prescription of febuxostat.…”

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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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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“…Furthermore, probenecid, which is the alternative to allopurinol, is relatively contraindicated in CKD because of concerns surrounding urolithiasis, as well as its low efficacy in the presence of kidney dysfunction. 6 Febuxostat, a novel and potent nonpurine selective xanthine oxidoreductase inhibitor, has been shown to be highly efficacious in reducing serum uric acid (sUA) levels. Because it is mainly metabolized by the liver, it is well tolerated in patients with mild-to-moderate kidney dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

et al. 2014

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Hyperuricemia (HU) is common in patients with chronic kidney disease (CKD), and accumulating evidence suggests it has a pathogenic role in the progression of the disease. However, a major challenge in treating patients with HU is the adverse effects caused by urate-lowering drugs used to treat CKD. Because of these untoward effects, doses need to be reduced, which leads to suboptimal efficacy. Febuxostat has been shown to be highly efficacious in reducing serum uric acid (sUA) and is well tolerated in patients with mild kidney dysfunction. However, its safety and efficacy have not been well studied in more advanced cases of CKD. We studied the safety and efficacy of escalating doses of febuxostat over a 24-week period in 70 patients with CKD stages 3b, 4 and 5, and we also observed the changes in blood pressure, estimated glomerular filtration rate (eGFR) and proteinuria following the reduction of sUA. Drug-related adverse events (AEs) occurred in only 5 out of 70 patients. All but one of the events were mild, and all five patients fully recovered. By 24 weeks, the reduction of sUA levels was >40% in CKD stage 3b and >50% in CKD stages 4 and 5. More than 70% of patients achieved target sUA levels of 6 mg dl(-1) or less. Multivariate analysis showed that a greater reduction in sUA with febuxostat was associated with an increase in eGFR and a tendency toward decreased proteinuria. Febuxostat was safe and efficacious in the treatment of CKD stages 3b-5.

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“…Recently, interleukin 1 inhibitors, such as anakinra, are being investigated as potential alternative treatments for refractory gout;15 however, anakinra also requires renal dosing. Thus, patients with chronic kidney disease are often limited in terms of therapeutic options, with febuxostat and uricase agents often being used, although the safety of these drugs in severe renal failure has not been reported 23. The American College of Rheumatology Guidelines also stress the importance of behavioural modification, including weight loss, smoking cessation and decreasing intake of purine-rich foods, such as meats, seafood and alcohol.…”

Section: Discussionmentioning

confidence: 99%

Ulcerated tophaceous gout

2015

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SUMMARYGout is an inflammatory arthritis characterised by hyperuricemia, which, if poorly controlled, can lead to the development of tophi. We report the case of a 60-year-old Caucasian man with poorly controlled polyarticular tophaceous gout with multiple comorbidities (including renal failure) who presented with tophaceous ulcers of the upper extremity. These ulcers caused extreme pain, requiring chronic opiate medications, and were associated with decreased sensation and reduced ability to move the extremity. His hospital course was complicated by acute kidney injury, haemolytic anaemia and Clostridium difficile infection. He required 1 month of antibiotics and intensive wound care for his ulcers. This case highlights the diagnosis, natural history and management of an unusual complication of hyperuricemia. BACKGROUND

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Challenges Associated with the Management of Gouty Arthritis in Patients with Chronic Kidney Disease: A Systematic Review

Cited by 49 publications

References 99 publications

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

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

Safety, efficacy and renal effect of febuxostat in patients with moderate-to-severe kidney dysfunction

Ulcerated tophaceous gout

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