Preservation of Renal Function during Gout Treatment with Febuxostat: A Quantitative Study

Whelton, Andrew; MacDonald, Penny A.; Chefo, Solomon; Gunawardhana, Lhanoo

doi:10.3810/pgm.2013.01.2626

Cited by 50 publications

(56 citation statements)

References 36 publications

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“…In an interventional study, Whelton et al [22] predicted that 1.15 mL of eGFR would be preserved for every 1 mg/dL reduction of serum uric acid in patients with gout. It is therefore pertinent that future clinical interventional studies examining hyperuricemia and renal function should include serum uric acid as an important parameter.…”

Section: Discussionmentioning

confidence: 99%

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study

Yang

Chang

et al. 2019

Med Princ Pract

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Objective: Recent studies have reported that reduced excretion of urinary uromodulin is associated with renal tubular function and risks of progressive kidney disease. Gouty nephropathy is usually seen in patients with gout. Patients with chronic gouty nephropathy are characterized by the deposition of monosodium urate crystals primarily involving the collecting ducts in the medulla. We postulated that this correlation may be specific to gout and may serve as a useful biomarker for chronic kidney disease (CKD). Materials and Methods: A total of 114 Taiwanese patients diagnosed with gout (n = 72), CKD (n = 26), or healthy volunteers (n = 16) were prospectively enrolled for this study from the Rheumatology and Nephrology Outpatient Clinics of our institution. We obtained urine and blood samples on patient visits to the outpatient clinics. Demographic data were obtained from medical records. Results: In patients with gout, the spot urinary uromodulin/creatinine ratio (uUMCR; mg/g) in patients with CKD was significantly lower than that in those without CKD (CKD group: 2.2; non-CKD group: 5.6, p = 0.005). Multivariate analysis revealed that patients with CKD and gout had a lower uUMCR than those with gout alone (p = 0.028). A significant association was not observed in our non-gout cohort. Conclusion: The association of decreased uUMCR with CKD status was identified only in patients with gout in the present study. We believe that uUMCR might serve as an indicator of differential CKD in patients with gout.

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Section: Discussionmentioning

confidence: 99%

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study

Yang

Chang

et al. 2019

Med Princ Pract

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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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“…They preserved their renal function for 12 months. In an open-label Febuxostat/Allopurinol Comparative Extension Long-Term (EXCEL) study, the effect of xanthine oxidase inhibitor on renal function was confirmed in 551 patients with gout, who had taken febuxostat for up to 4 years [27]. In this study, the continuous reduction of SUA level was related to a slower decrease of renal function (p＜0.001).…”

Section: The Kidney and Uric Acidmentioning

confidence: 72%

“…In this study, the continuous reduction of SUA level was related to a slower decrease of renal function (p＜0.001). This study showed that a sustained reduction of 1 mg/dl of SUA was correlated with the preservation of 1.15 ml/min of GFR [27]. However, ongoing prospective trials are needed to confirm the effect of febuxostat on the decline of GFR over an extended period in patients with CKD and hyperuricemia without deposition [28].…”

Section: The Kidney and Uric Acidmentioning

confidence: 88%

Hyperuricemia and Urologic Disease

Cho

Min

2017

Urogenit Tract Infect

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Gout is a disease that causes painful inflammatory arthritis related to hyperuricemia, due to the incorrect metabolism of uric acid. Decreased renal excretion of urate is thought to be the major hyperuricemic mechanism. Most genes responsible for the serum uric acid (SUA) level encode uric acid transporters or related regulatory proteins. The acquired effects can also modulate SUA level and uric acid excretion, which can result in acute gout. Interestingly, kidney related comorbidities in gout, such as hypertension, chronic kidney disease (CKD), and urolithiasis, all have a fairly high prevalence. Recent advancements in genetics and molecular physiology have greatly improved our understanding of renal reabsorption and secretion of filtered uric acid. Furthermore, the baseline SUA level appears to be established by a net balance between absorption and secretion through the epithelium of the kidneys and intestines. There have also been considerable progress in the management of gout patients with CKD. Increased prevalence of gout with CKD can be balanced by an expanded spectrum of treatment options for this important disease. Another issue is that lowering of the uric acid level can reduce the incidence of cardiovascular disease, renal disease, and urological complications. Basic research and clinical studies on these mechanisms might be helpful in determining the appropriate treatment for hyperuricemic patients. Based on currently existing literature, there have been improvements associated with medications that lower uric acid, particularly xanthine oxidase inhibitors. Here, we review the pathogenesis and epidemiology of hyperuricemia, specific diseases related to uric acid, and up-to-date perspectives on their management.

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Preservation of Renal Function during Gout Treatment with Febuxostat: A Quantitative Study

Abstract: Sustained urate-lowering therapy with febuxostat appears to impede renal decline in patients with gout. The results discussed in this article support similar observations previously reported in 116 hyperuricemic subjects with gout who received febuxostat for ≤ 5 years.

Cited by 50 publications

References 36 publications

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study

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

Hyperuricemia and Urologic Disease

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