The Clinical Effects of New Non-Purine Xanthine Oxidase Inhibitor, Febuxostat, in Patients with Chronic Kidney Disease

AbstractAs previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

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A REVIEW ON THE EFFECT OF FEBUXOSTAT IN CHRONIC KIDNEY PATIENTS, IT’S SIGNIFICANCE IN eGFR, URIC ACID AND ALBUMINURIA.

International Journal of Pharmaceutical and Biological Science Archive ◽

10.32553/ijpba.v7i2.121 ◽

2019 ◽

Vol 7 (2) ◽

Author(s):

Jinsu Deena Jose ◽

Mathew George ◽

Lincy Joseph

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Uric Acid ◽

Kidney Disease ◽

Uric Acid Level ◽

Acid Level ◽

Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitor ◽

Irreversible Reduction ◽

Risk Of Progression

Chronic kidney disease is defined as the abnormality of the kidney structure or function for≥ 3 months and is associated with an irreversible reduction of the excretory and the endocrine functions of the kidney. An important risk factor for the development and progression of CKD is hyperuricemia. Hyperuricemia can occur as a result of the increased production or the reduced secretion of uric acid. Increased uric acid level is significantly associated with a greater decline in renal function and there is a higher risk of progression into kidney failure. Febuxostat is a nonpurine xanthine oxidase inhibitor for the treatment of hyperuricemia in patients with chronic kidney disease. It reduces serum uric acid concentrations by blocking the transformation of hypoxanthine to xanthine and xanthine to uric acid. Febuxostat is mainly metabolized in the liver and excreted through both urine and feces. Renal adjustment is also not required in CKD patients with mild to moderately reduced eGFR as it is metabolized mainly by glucuronidation and oxidation in the liver and well excreted by both urinary and fecal routes. Recent studies show that, in addition to lowering the uric acid level, febuxostat preserves the eGFR. Keywords: Chronic kidney disease, hyperuricemia, febuxostat, eGFR

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MP493NOVEL XANTHINE OXIDASE INHIBITOR TEI-B AMELIORATES URINARY ALBUMIN EXCRETION IN NORMOURICEMIC DIABETIC KIDNEY DISEASE MODELS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx174.mp493 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii609-iii609

Author(s):

Takashi Shirakura ◽

Shunsuke Tsujimoto ◽

Yoshiki Tsubosaka ◽

Reiko Aizawa ◽

Chieko Matsui ◽

...

Keyword(s):

Kidney Disease ◽

Xanthine Oxidase ◽

Diabetic Kidney Disease ◽

Urinary Albumin Excretion ◽

Oxidase Inhibitor ◽

Urinary Albumin ◽

Disease Models ◽

Xanthine Oxidase Inhibitor ◽

Diabetic Kidney ◽

Albumin Excretion

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The Effect of Alopurinol on Blood Urea Nitrogen and Creatinine Serum Levels in Patients with Chronic Kidney Disease

Journal of Agromedicine and Medical Sciences ◽

10.19184/ams.v7i1.10928 ◽

2021 ◽

Vol 7 (1) ◽

pp. 8

Author(s):

Miftakhul Huda ◽

Pulong Wijang Pralampita ◽

Dini Agustina ◽

Cholis Abrori ◽

Septa Surya Wahyudi

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Serum Creatinine ◽

Xanthine Oxidase ◽

Kidney Function ◽

Blood Urea Nitrogen ◽

Secondary Data ◽

Urea Nitrogen ◽

Xanthine Oxidase Inhibitor

Chronic kidney disease (CKD) is a structural and function disorder of renal for > 3 months with implications for individual health. CKD has become a health problem throughout the world and its implementation provides a considerable economic burden on the health system. The decreasing value of GFR (glomerular filtration rate) in CKD can cause uric acid retention so that serum uric acid levels increase (hyperuricemia). Hyperuricemia can occur due to an increase in urinary metabolism (overproduction), a decrease in uric acid expenditure (underexcretion), or a combination of both. The group of antihyperuricemic drugs that have good effectiveness and long-term safety is xanthine oxidase inhibitors. The commonly used xanthine oxidase inhibitor drug is allopurinol. The purpose of this study was to determine whether there was an effect of allopurinol on kidney function in CKD patients. The results of this study are expected to provide input in the treatment of hyperuricemia in CKD patients and reduce the progression of CKD. This study used a retrospective observational analytic design with a cross-sectional approach. The study population was CKD patients from January 2018 to January 2019 at Bina Sehat Hospital Jember. The sampling technique uses purposive sampling. This study uses secondary data obtained from medical records of CKD patients at Bina Sehat Hospital Jember. Secondary data obtained in the form of identity data and the results of laboratory tests of patients. The medical record data that has been obtained is distributed and analyzed using a paired T-test to compare the mean or mean differences of the two groups in pairs. The bivariate test results for blood urea nitrogen and serum creatinine levels in CKD patients were obtained p <0.001. Based on these results there is a significant relationship between blood urea nitrogen and serum creatinine levels before and after consuming allopurinol. The conclusion was that allopurinol was shown to be able to provide an effect on the kidney function of CKD patients based on blood urea nitrogen and serum creatinine levels. Keywords: Chronic kidney disease, hyperuricemia, allopurinol

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Hyperuricemia Resistant to a Xanthine Oxidase Inhibitor, Topiroxostat: a Case Report

10.21203/rs.3.rs-538083/v1 ◽

2021 ◽

Author(s):

Takahide Kimura ◽

Seiki Yamada ◽

Masayuki Tanemoto

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Xanthine Oxidase ◽

Oxidase Inhibitor ◽

Uric Acid Concentration ◽

Common Complication ◽

Xanthine Oxidase Inhibitor ◽

Xanthine Oxidase Inhibitors ◽

Serum Uric Acid Concentration ◽

Rate Limiting

Abstract Hyperuricemia is a common complication of chronic kidney disease. Gout is a clinical symptom of hyperuricemia, and lowering serum uric acid concentration has been recommended to prevent its recurrence. We present a case whose hyperuricemia was resistant to a xanthine oxidase inhibitor, febuxostat, but not another inhibitor, topiroxostat, while both are presumed to inhibit the same enzymatic center of this rate-limiting enzyme for uric acid production. The different efficacy indicates that xanthine oxidase inhibitors are not interchangeable even among those acting on the same site of the enzyme.

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Management of Hyperuricemia in Patients with Chronic Kidney Disease: a Focus on Renal Protection

Current Hypertension Reports ◽

10.1007/s11906-020-01116-3 ◽

2020 ◽

Vol 22 (12) ◽

Author(s):

Jan T. Kielstein ◽

Roberto Pontremoli ◽

Michel Burnier

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Uric Acid ◽

Kidney Disease ◽

Current Knowledge ◽

Oxidase Inhibitor ◽

Renal Protection ◽

Xanthine Oxidase Inhibitor ◽

Lowering Therapy ◽

Clinical Conditions

Abstract Purpose of Review In chronic kidney disease (CKD), plasma uric acid levels are increased because of the decrease in glomerular filtration rate. However, in addition to CKD, hyperuricemia is frequently associated with a number of other conditions such as hypertension, type 2 diabetes, obesity, and heart failure, overweight, and cardiovascular disease. Recent Findings It is now becoming increasingly clear that, in many clinical conditions, elevated levels of uric acid have a much greater role beyond just causing gout. The present review will summarize current knowledge on the relation between hyperuricemia, CKD, and existing comorbidities, as well as the mechanisms of uric acid–related renal damage. In addition, the role and evidence for urate-lowering therapy in prevention and cardiovascular protection in CKD patients is discussed with a focus on allopurinol and febuxostat. To date, several clinical studies have provided evidence that urate-lowering therapy may help to prevent and delay the decline of renal function in patients with CKD. Summary Use of a xanthine oxidase inhibitor should be considered in patients who are at high renal risk and/or with declining renal function in the presence of hyperuricemia with and without deposition, although additional studies are warranted to define treatment targets. Notwithstanding, the possibility to delay deterioration of renal function in patients with CKD merits consideration.

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AB0646 COMPARATIVE ANALYSIS OF ASYMPTOMATIC HYPERURICEMIA AND GOUT - AN IMPACT ON KIDNEY STRUCTURE AND FUNCTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4306 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1356.1-1356

Author(s):

M. Hristova ◽

A. Kundurdzhiev ◽

T. Kundurzhiev ◽

R. Gancheva

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Urine Analysis ◽

Interstitial Fibrosis ◽

Structural Parameters ◽

Population Level ◽

Oxidase Inhibitor ◽

Tubular Atrophy ◽

Xanthine Oxidase Inhibitor ◽

The Impact

Background:The significance of asymptomatic hyperuricemia (AH) continues to be debated. At the population level, asymptomatic hyperuricemia is associated with multiple comorbidities, including hypertension, coronary artery disease, diabetes and chronic kidney disease.1Objectives:To investigate the impact of asymptomatic hyperuricemia on renal functional and structural parameters in comparison with symptomatic gout.Methods:The subjects included in the study were divided into two groups - 46 patients with asymptomatic hyperuricemia and 18 diagnosed with gout according to ACR/EULAR 2015 criteria.2 For renal function assessment urine analysis, albuminuria, estimated glomerular filtration rate (eGFR) based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used. Diagnostic ultrasound as well as renal biopsy were performed to evaluate structural and histological kidney changes. Statistical analysis was performed using SPSS 22.0 software (SPSS Inc, Chicago, USA).Results:There were no significant differences between the two groups on serum uric acid levels, albuminuria, and eGFR. However, erythrocyturia (p=0.047) and nephrolithiasis (p<0.001) prevailed significantly in patients with gout, 66.7% and 61.1% respectively. We did not find any histological differences between the two groups regarding the number of affected glomeruli, tubular atrophy and percentage of interstitial fibrosis based on light microscopy scans.Conclusion:Our results indicate that patients with AH need renal screening since both AH and gout show similar kidney changes. Further research is needed to elucidate the role of early treatment with xanthine oxidase inhibitor for asymptomatic hyperuricemia as prevention of complications such as erythrocyturia and nephrolithiasis.References:[1]Yip K, Cohen RE, Pillinger MH. Asymptomatic hyperuricemia: is it really asymptomatic? CurrOpin Rheumatology 2020; 32(1):71-79 doi: 10.1097/BOR.0000000000000679.[2]Neogi T, Jansen TL, Dalbeth N et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatogy 2015;67(10):2557-68. doi: 10.1002/art.39254.Disclosure of Interests:None declared.

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Clinical Effects of Xanthine Oxidase Inhibitors in Hyperuricemic Patients

Medical Principles and Practice ◽

10.1159/000512178 ◽

2020 ◽

Author(s):

Arrigo F.G. Cicero ◽

Federica Fogacci ◽

Raffaele Ivan Cincione ◽

Giuliano Tocci ◽

Claudio Borghi

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

English Language ◽

Clinical Evidence ◽

Oxidase Inhibitor ◽

Clinical Effects ◽

Xanthine Oxidase Inhibitor ◽

Positive Effects ◽

Xanthine Oxidase Inhibitors ◽

First Choice

This review aim is to critically resume the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine-oxidase inhibitor activity. For this reason, all of the studies published in English language from 2000 to August 2019 on uric acid-lowering drugs have been carefully reviewed. The terms “serum uric acid”, “xanthine oxidase”, “allopurinol”, “febuxostat”, and “topiroxostat” have been incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence: On the contrary, large long-term clinical trials have clearly demonstrated that xanthine oxidase inhibitors (namely, allopurinol and febuxostat) are effective, safe and relatively well-tolerated in the most part of patients. They have been largely tested in elderly, in patients affected by crhonic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function and glucose metabolism. Their cost is also low. In conclusion, xanthine oxidase inhibitors remain the first choice uric acid lowering drug for chronic treatment.

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