Comparative Renoprotective Effect of Febuxostat and Allopurinol in Predialysis Stage 5 Chronic Kidney Disease Patients: A Nationwide Database Analysis

Hsu, Yun‐Shiuan Olivia; Wu, I‐Wen; Chang, Shang‐Hung; Lee, Cheng‐Chia; Tsai, Chung‐Ying; Lin, Chan‐Yu; Lin, Wan‐Ting; Huang, Yu‐Tung; Wu, Chao‐Yi; Kuo, George; Hsiao, Chih‐Yen; Lin, Hsing‐Lin; Yang, Chih‐Chao; Yen, Tzung‐Hai; Chen, Yung‐Chang; Hung, Cheng‐Chieh; Tian, Ya‐Chong; Kuo, Chang‐Fu; Yang, Chih‐Wei; Anderson, Gerard F.; Yang, Huang‐Yu

doi:10.1002/cpt.1697

Cited by 19 publications

(15 citation statements)

References 44 publications

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“…By analyzing the U.S. Medicare claims data, they concluded that no difference was observed in the risk of myocardial infarction, stroke, new-onset heart failure, coronary revascularization, or all-cause mortality between patients initiating febuxostat and allopurinol [ 103 ]. Similar results were reported in the population-based cohort studies published by Hsu et al and Chen et al [ 98 , 104 ]. In 2020, a meta-analysis of 17 clinical trials reported that no statistical difference was observed in the risk of major adverse cardiovascular events and cardiovascular events between febuxostat and allopurinol treatment groups [ 105 ].…”

Section: Treatment and Evidence Of Clinical Trialssupporting

confidence: 91%

“…The adjusted hazard ratio was 0.65 and 0.66 for long-term dialysis and long-term dialysis or death with febuxostat use, respectively. This study revealed that in the CKD stage 5 predialysis patients, febuxostat users had a lower risk of progression to long-term dialysis or death compared to allopurinol users [ 98 ]. Chung et al had published another study investigating the impact of ULT on the progression and recovery of CKD by analyzing 5860 gout patients.…”

Section: Treatment and Evidence Of Clinical Trialsmentioning

confidence: 99%

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Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

Lee

Chen

et al. 2021

Diagnostics

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The relationship between hyperuricemia, gout, and renal disease has been investigated for several years. From the beginning, kidney disease has been considered a complication of gout; however, the viewpoints changed, claiming that hypertension and elevated uric acid (UA) levels are caused by decreased urate excretion in patients with renal impairment. To date, several examples of evidence support the role of hyperuricemia in cardiovascular or renal diseases. Several mechanisms have been identified that explain the relationship between hyperuricemia and chronic kidney disease, including the crystal effect, renin–angiotensin–aldosterone system activation, nitric oxide synthesis inhibition, and intracellular oxidative stress stimulation, and urate-lowering therapy (ULT) has been proven to reduce renal disease progression in the past few years. In this comprehensive review, the source and physiology of UA are introduced, and the mechanisms that explain the reciprocal relationship between hyperuricemia and kidney disease are reviewed. Lastly, current evidence supporting the use of ULT to postpone renal disease progression in patients with hyperuricemia and gout are summarized.

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Section: Treatment and Evidence Of Clinical Trialssupporting

confidence: 91%

Section: Treatment and Evidence Of Clinical Trialsmentioning

confidence: 99%

Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

Lee

Chen

et al. 2021

Diagnostics

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“…When comparing the all-cause mortality of the two XOis, febuxostat has been found as both comparable and at higher risk to allopurinol (37). However, in our previous study, febuxostat was associated with superior renoprotection without compromising survival compared to allopurinol in CKD 5 patients (38). Without a consensus, further studies focusing on the mortality risk of the different XOis in CKD 5 patients are necessary.…”

Section: Discussionmentioning

confidence: 81%

Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study

et al. 2022

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BackgroundAdvanced chronic kidney disease (CKD) patients are at higher risk of sepsis-related mortality following infection and bacteremia. Interestingly, the urate-lowering febuxostat and allopurinol, both xanthine oxidase inhibitors (XOis), have been suggested to influence the sepsis course in animal studies. In this study, we aim to investigate the relationship between XOis and infection/sepsis risk in pre-dialysis population.MethodsPre-dialysis stage 5 CKD patients with gout were identified through the National Health Insurance Research Database (NHIRD) in Taiwan from 2012 to 2016. Outcomes were also compared with national data.ResultsIn our nationwide, population-based cohort study, 12,786 eligible pre-dialysis stage 5 CKD patients were enrolled. Compared to non-users, febuxostat users and allopurinol users were associated with reduced sepsis/infection risk [hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.87–0.99; P = 0.0324 vs. HR, 0.92; 95% CI, 0.86–0.99; P = 0.0163]. Significant sepsis/infection-related mortality risk reduction was associated with febuxostat use (HR, 0.68; 95% CI, 0.52–0.87). Subgroup analysis demonstrated preference of febuxostat over allopurinol in sepsis/infection-related mortality among patients younger than 65 years of age, stain users, non-steroidal anti-inflammatory drug non-users, and non-diabetics. There was no significant difference in major adverse cardiac and cerebrovascular event (MACCE) risk between users and non-users while reduced risk of all-cause mortality was observed for XOi users.ConclusionsUse of XOi in pre-dialysis stage 5 CKD patients may be associated with reduced risk of sepsis/infection and their related mortality without increased MACCE and overall mortality.

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“…However, several of these studies had small sample sizes [ 28 , 29 ]. Another major caveat of other studies was a short median follow-up duration of less than one year [ 28 , 30 ]. Because allopurinol can cause acute reduction in GFR due to reduced glomerular pressure [ 4 ], a sufficient study duration is required to adequately capture its effect on CKD.…”

Section: Discussionmentioning

confidence: 99%

Superior effect of allopurinol compared to febuxostat on the retardation of chronic kidney disease progression

et al. 2022

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Background Although hyperuricemia is associated with chronic kidney disease, whether and how it should be managed for renoprotection remains debatable. Thus, we investigated whether allopurinol and febuxostat, the most frequently used urate-lowering treatments, have differential renoprotective effects on chronic kidney disease. Methods Incident users of allopurinol and febuxostat were identified from two tertiary referral centers. One-to-one propensity score matching between the allopurinol and febuxostat groups was performed. Participants were followed up until the occurrence of clinical outcomes, urate-lowering agent discontinuation, mortality, or the end of the study period, whichever occurred first. The primary outcomes were a 30% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease. Differential trends of eGFR decline were estimated using a linear mixed-effects model. Results Each group included 654 participants. Baseline eGFRs were 40.1 [26.6–57.3] and 39.1 [27.9–58.3] mL/min/1.73 m2 in the allopurinol and febuxostat group, respectively. Adjusted least square mean change in serum urate was −1.58 mg/dL [95% confidence interval (CI), −1.78 to −1.38] and -2.69 mg/dL (95% CI, −2.89 to −2.49) in the allopurinol and febuxostat groups, respectively. Despite lower serum urate levels, febuxostat was significantly more associated with a 30% decline in eGFR (hazard ratio 1.26; 95% CI 1.03–1.54) and end-stage renal disease (hazard ratio 1.91, 95% CI 1.42–2.58) than allopurinol. Annual eGFR decline in febuxostat users was estimated to be more rapid than in allopurinol users by 2.14 (standard error 0.71) mL/min/1.73 m2 per year. Conclusions Allopurinol demonstrated attenuation of chronic kidney disease progression and prevention of hypouricemia, compared to febuxostat. Because the treatment can be renoprotective, further studies on its effects on chronic kidney disease are required.

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Comparative Renoprotective Effect of Febuxostat and Allopurinol in Predialysis Stage 5 Chronic Kidney Disease Patients: A Nationwide Database Analysis

Cited by 19 publications

References 44 publications

Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

Reduced Risk of Sepsis and Related Mortality in Chronic Kidney Disease Patients on Xanthine Oxidase Inhibitors: A National Cohort Study

Superior effect of allopurinol compared to febuxostat on the retardation of chronic kidney disease progression

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