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Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.
Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.
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@#Periodontitis is associated with abnormal purine metabolism, which is manifested by increased uric acid in host blood and increased expression of the purine-degrading enzyme, xanthine oxidoreductase (XOR), in periodontal tissues. Both XOR and uric acid are pro-oxidative and pro-inflammatory mediators under pathological conditions. Animal studies have found that injection of uric acid promotes the progression of periodontitis and that febuxostat (an XOR inhibitor) improves tissue destruction in periodontitis. Therefore, blocking the source of uric acid may be a therapeutic strategy to control the progression of periodontitis. In this article, the rationality of XOR inhibitors as potential therapeutic drugs for periodontitis is reviewed. The literature review results suggest that XOR inhibitors show antioxidative, anti-inflammatory, and anti-osteoclastic effects, and XOR inhibitors show clinical efficacy in the treatment of infectious, inflammatory and osteolytic diseases. Although there is no direct evidence to support the finding that XOR inhibitors can ameliorate periodontal microecological dysbiosis, these drugs can modulate intestinal microflora dysbiosis, and there is indirect evidence to support a beneficial effect of XOR inhibitors on periodontal microecological dysbiosis. In conclusion, XOR inhibitors may be used as immunomodulators for the adjuvant treatment of periodontitis by inhibiting inflammation, oxidative stress and anti-osteoclast effects.
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Objective:To evaluate the effect of febutostat on vascular endothelial function, intima-media thickness(C-IMT) and elasticity of the carotid artery in patients with asymptomatic hyperuricemia.Methods:This study was a randomized controlled clinical trial that enrolled asymptomatic hyperuricemia patients from the outpatient and inpatient departments of Huai′an First People′s Hospital from October 2018 to October 2020. The participants were randomly divided into two groups: the Febuxostat group and the control group. Serum triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), nitric oxide(NO), endothelin-1(ET-1), malondialdehyde(MDA), and superoxide dismutase(SOD) were measured at baseline and 1, 3, and 6 months after treatment, and brachial artery flow-mediated dilation(FMD) was quantified by color Doppler ultrasound. The following parameters of the common carotid artery were detected at baseline and 12 months after treatment: C-IMT, arterial compliance(AC), one-point pulse wave velocity(PWV), stiffness index(β), and pressure-strain elasticity modulus(Ep). The differences before and after treatment and between the two groups were compared. Pearson correlation was used to analyze the correlation between ΔUA and ΔNO, ΔET-1, ΔC-IMT, ΔAC, Δβ, ΔEp, and ΔPWVβ after treatment with febuxostat. Results:Compared with baseline, TG, HOMA-IR, ET-1 and MDA were significantly lower, while FMD, NO and SOD were significantly higher after 3-months treatment with febuxostat. After 12-months treatment, there was no significant difference in C-IMT or Ep, but there was an increase in AC and a decrease in PWVβ or β compared with baseline. There was a negative correlation between ΔFMD and ΔUA( r=-0.403, P=0.004), but there were no correlations between ΔNO and ΔUA( r=-0.187, P=0.194), ΔET-1 and ΔUA( r=0.038, P=0.791) after 6-months treatment. And ΔUA was an independent factor for ΔFMD( F=2.94, P=0.003, adjusted R2=0.139). After 12-months treatment, there was a negative correlation between ΔAC and ΔUA, and a positive correlation between ΔPWVβ and ΔUA, but there were no correlations between the following indicators: ΔC-IMT and ΔUA( r=0.169, P=0.240), Δβ and ΔUA( r=-0.214, P=0.136), ΔEp and ΔUA( r=-0.077, P=0.597). In the control group, there were no differences among the above indicators between each follow-up time and baseline. Conclusion:Febuxostat improves vascular endothelial function and elasticity in patients with asymptomatic hyperuricemia, which may be related to the decreased oxidative stress response.
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OBJE CTIVE To mine and analyze t he cardiac adverse drug reaction （ADR）signals induced by febuxostat in post-marketing experience ，and to provide reference for rational drug use in clinic. METHODS Reporting odds ratio （ROR） method was used to mine the ADR signals induced by febuxostat from the FDA Adverse Event Reporting System during the first quarter of 2009 to the fourth quarter of 2020；the information of cardiac disease signals was counted and analyzed. RESULTS A total of 209 ADR signals were detected in 8 282 adverse drug event （ADE）reports with febuxostat as the primary suspected drug ， involving 27 cardiac signals and 754 ADE reports. The most reported signals were symptoms （262 reports），including dizziness ， oedema peripheral，chest pain ，palpitations and gravitational oedema and so on ，followed by coronary atherosclerotic heart disease signal，heart failure signal ，arrhythmia signal ，sudden cardiac death signal （233，157，90，12 reports，respectively）. More than half of the signals were mentioned in the drug instructions ，while the unmentioned signals were mainly kinds of cardiac failure ， arrhythmia and extrasystoles ，etc. The patients with cardiac ADEs who received febuxostat were more male than female ，and the age was 60 and over ；the drug dosage was mostly 40 mg/d or 80 mg/d as recommended in the drug instructions ，and cardiac ADEs mostly occurred within 1 month of medication. CONCLUSIONS Routine attention should be paid to the cardiac safety of febuxostat during medication ，further evaluation and validation of febuxostat-induced cardiac ADR signals are still needed.
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Objective:To investigate the risk factors of hyperuricemia (HUA) in non-dialysis diabetic nephropathy (DN) patients, and to observe the protective effect of febuxostat on kidney.Methods:The clinical data of 317 DN patients without dialysis in Affiliated Hospital of Hebei University from January 2018 to February 2021 were analyzed retrospectively. Among them, HUA occurred in 148 cases (HUA group), the incidence of HUA was 46.69%, and no HUA occurred in 169 cases (non-HUA group). In HUA group, 74 patients were treated with febuxostat (observation subgroup), and 74 patients with allopurinol (control subgroup). Multivariate Logistic regression analysis was used to analyze the independent risk factors of HUA in patients with DN; a nomogram model for predicting the occurrence of HUA in patients with DN was established by R 4.0.2 software, the predictive ability of the nomogram model was evaluated by receiver operating characteristic (ROC) curve, and the calibration and validity of the prediction model were verified by correction curve and deviation correction C-index.Results:There were no significant difference in gender composition and the incidence of diabetic retinopathy, diabetic peripheral neuropathy, diabetic foot between the two groups ( P>0.05); the age, body mass index (BMI), DN course>3 years rate, smoking rate, drinking rate, family history of diabetes rate, seafood consumption more than 2 times a week rate, and the incidences of hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke in HUA group were significantly higher than those in non-HUA group: (57.96 ± 5.25) years old vs. (56.14 ± 4.71) years old, (24.18 ± 3.95) kg/m 2 vs. (23.06 ± 3.12) kg/m 2, 78.38% (116/148) vs. 30.77% (52/169), 84.46% (125/148) vs. 28.99% (49/169), 93.92% (139/148) vs. 40.24% (68/169), 62.84% (93/148) vs. 50.30% (85/169), 46.62% (69/148) vs. 15.38% (26/169), 41.89% (62/148) vs. 20.71% (35/169), 73.65% (109/148) vs. 45.56% (77/169), 39.86% (59/148) vs. 18.34% (31/169), 45.95% (68/148) vs. 26.04% (44/169) and 50.68% (75/148) vs. 8.28% (14/169), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption were independent risk factors for HUA in patients with DN ( OR = 1.053, 1.062, 3.192, 3.638, 5.397, 1.371, 1.690, 1.404, 1.392, 2.295 and 2.581; 95% CI 1.028 to 1.078, 1.031 to 1.093, 2.517 to 3.867, 2.754 to 4.522, 4.169 to 6.625, 1.253 to 1.489, 1.482 to 1.898, 1.237 to 1.571, 1.284 to 1.501, 1.730 to 2.860 and 1.862 to 3.300; P<0.01), but the family history of diabetes was not related to the occurrence of HUA in DN patients ( P>0.05). A nomogram model was established based on age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption as predictors of HUA in patients with DN; the results of correction curve analysis show that the actual curve was consistent with the ideal curve, and the prediction of HUA in patients with DN by the nomogram model was consistent with the actual situation (C-index was 0.931, 95% CI 0.895 to 0.967). The results of ROC curve analysis show that the nomogram model had a strong ability to predict the occurrence of HUA in patients with DN (the area under the curve was 0.855, 95% CI 0.842 to 0.868). The total effective rate in observation subgroup was significantly higher than that in control subgroup: 93.24% (69/74) vs. 70.27% (52/74), the levels of uric acid, creatinine and urea nitrogen after treatment were significantly lower than those in control subgroup: (314 ± 65) μmol/L vs. (392 ± 75) μmol/L, (227 ± 46) μmol/L vs. (271 ± 53) μmol/L and (13.52 ± 2.47) mmol/L vs. (16.80 ± 3.05) mmol/L, and there were statistical differences ( P<0.01). Conclusions:The age, BMI, course of DN, smoking, drinking, hypertension, hyperlipidemia, coronary heart disease, nephrolithiasis, stroke and weekly seafood consumption are independent risk factors for HUA in patients with DN. Febuxostat can effectively protect the renal function of patients with DN complicated with HUA.
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Febuxostat, as a xanthine oxidase inhibitor, is a classic anti-gout drug with significant therapeutic effects and good tolerability. The structures of febuxostat and its derivatives can be divided into two parts: a substituted phenyl ring and a five-membered or six-membered heterocyclic ring with a carboxyl substitution. This paper reviewed the research progress of febuxostat derivatives in recent ten years and classified the structure-activity relationships of various febuxostat derivatives. Exploring the action mechanisms and structure-activity relationships of xanthine oxidase inhibitors might be significant for the rational design and development of new anti-gout chemical entities.
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@#Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease. Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals. Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported. Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.
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ABSTRACT Objective: To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients. Methods: Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week. Results: No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P<0.05). There was no difference in 24-hour urine protein quantification, albuminuria, and creatinine ratio between two groups before treatment, and significant differences were observed after treatment. Fifty percent of patients from the treatment group achieved the treatment goal with 20 mg febuxostat at 4 weeks. Tubular markers were also decreased with the treatment. Conclusions: Febuxostat can reduce uric acid and improve renal function effectively in patients with CKD stage 3 diabetic nephropathy, while being well tolerated. However, the conclusion is still uncertain due to the short term of the study.
RESUMO Objetivo: Investigar a eficácia e segurança do febuxostat na função renal em pacientes com DRC estágio 3, com nefropatia diabética. Métodos: Foram recrutados pacientes em nosso hospital com nefropatia diabética (DN) estágio 3 de doença renal crônica (DRC) complicada por ácido úrico sérico alto (360 µmol/L). Os pacientes foram então divididos em grupo de tratamento e grupo controle, de acordo com o método da tabela de números aleatórios. Todos os pacientes receberam dieta pobre em purinas, inibidores do sistema renina-angiotensina-aldosterona (RAAS) e tratamento hipoglicêmico de rotina. O Febuxostat foi empregado apenas no grupo de tratamento. Os níveis de ácido úrico no sangue (AIU), creatinina sérica (Scr), cistatina C (cys-c), TFGe, quantificação de proteínas na urina em 24 horas, razão albumina e creatinina (ACR) foram avaliados em todos os pacientes antes e após o tratamento às 4, 8, 12 e 24 semanas. Resultados: Nenhuma diferença foi encontrada antes do tratamento entre os dois grupos. Após o tratamento nas 4, 8, 12 e 24 semanas, os níveis de sUA, SCr, cys-c e TFGe entre os dois grupos foram significativamente diferentes (P <0,05). Não houve diferença na quantificação de proteínas na urina em 24 horas, albuminúria e razão de creatinina entre dois grupos antes do tratamento, e diferenças significativas foram observadas após o tratamento. Cinquenta por cento dos pacientes do grupo de tratamento atingiram a meta de tratamento com 20 mg de febuxostat em 4 semanas. Marcadores tubulares também foram reduzidos com o tratamento. Conclusões: O Febuxostat pode reduzir o ácido úrico e melhorar a função renal efetivamente em pacientes com nefropatia diabética estágio com DRC no estágio 3, sendo bem tolerado. No entanto, a conclusão ainda é incerta devido ao curto prazo do estudo.
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Humans , Diabetes Mellitus , Diabetic Nephropathies/drug therapy , Uric Acid , China , Febuxostat/therapeutic use , Kidney/physiologyABSTRACT
Gout is one of the most common forms of acute inflammatory arthritis caused by long-standing hyperuricemia. Various clinical and epidemiological studies have demonstrated that uric acid, which is strongly associated with the pathogenesis of gout, is closely related with increased cardiovascular (CV) risk. Thus, properly controlling uric acid levels within its physiological level using urate-lowering therapy has been hypothesized to improve CV outcomes. Recently, however, on the basis of the results of the largest prospective, the double-blind, randomized controlled trial, entitled “the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES),” has aroused the possibility of increased CV-related and all-cause mortality in patients receiving febuxostat. Largely on the basis of this unpredicted result, the US and Korea Food and Drug Administration issued a public safety alert concerning the high risk of CV death with the use of febuxostat in February 2019. This unexpected announcement left many rheumatologists confused when they decide the first-line urate-lowering drug in Korea. In this review, we searched for previous studies on uric acid and increased risk of CV disease. In addition, we will introduce various interpretations of the results of the CARES trial and discuss the best choice of urate-lowering therapy for Korean.
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OBJECTIVE: To compare efficacy and safety of febuxostat in gouty patients with chronic kidney disease (CKD) stage 3 and stage 4/5. METHODS: Age and sex matched patients with CKD stage 3 and stage 4/5 who were diagnosed with gout were included. The dose of febuxostat was increased according to serum uric acid (sUA) level. Adherence, the number of gout attack, the change of sUA, the change of estimated glomerular filtration rate (eGFR) and adverse events (AEs) were evaluated for 12 months. RESULTS: There were no significant differences in the baseline variables between CKD stage 3 and CKD stage 4/5. Disease duration was longer and baseline sUA was higher in the CKD stage 4/5. There were no significant differences in the mean sUA at the last follow-up, the number of patients who reached the sUA target of 6 mg/dL and the number of gout attack between the groups. There were no significant differences in the change of eGFR and decrease of eGFR between the groups. There were 2 cases of AEs. One patient in CKD stage 3 had maculopapular rash and one patient in CKD stage 4/5 had dizziness. The AEs were subsided after febuxostat was stopped. CONCLUSION: Febuxostat was efficacious and well tolerated in gout patients with CKD stage 4/5.
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Humans , Dizziness , Exanthema , Febuxostat , Follow-Up Studies , Glomerular Filtration Rate , Gout , Renal Insufficiency, Chronic , Uric AcidABSTRACT
Objective@#To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease (CKD) stages 3-5 patients with hyperuricemia (HUA).@*Methods@#The study was a prospective cohort study. The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed. The patients were assigned to febuxostat (A) group, allopurinol (B) group and non-hyperuricemia (C) group according to the level of serum uric acid and the choice of urate-lowering drugs. Serum uric acid, hypersensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and endothelin-1 (ET-1) were measured at baseline, 1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared. According to the level of serum uric acid, patients were divided into attainment group and nonattainment group, and the correlation between uric acid and oxidative stress was analyzed at baseline and 3 months after treatment respectively.@*Results@#There was no significant difference in baseline levels of serum uric acid, inflammation and oxidative stress between group A and group B (P>0.05). The levels of serum uric acid, hs-CRP, MDA and ET-1 of group A and group B were significantly higher than those of group C, but the level of SOD of group A and group B was significantly lower than that of group C at baseline (P<0.001). After treatment for 1 month and 3 months, the values of serum uric acid, hs-CRP, MDA and ET-1 in group A were significantly lower than those in group B, while the level of SOD in group A was significantly higher than that in group B (P<0.001). Compared with pre-treatment period, both the serum uric acid, hs-CRP, MDA and ET-1 levels of group A and group B were declined significantly while SOD had a significant rise after 3 months treatment (P<0.001). The changes of group A were significantly higher than those of group B (P<0.001). At baseline and 3 months after treatment, serum uric acid was positively related to hs-CRP, MDA and ET-1, but negatively related to SOD in nonattainment group (| r|>0.50, P<0.001); serum uric acid was positively related to hs-CRP, MDA and SOD (| r|>0.70, P<0.001), and there was no correlation between serum uric acid and ET-1 in attainment group (P>0.05).@*Conclusions@#Febuxostat performed better than allopurinol in lowering urate and inhibiting oxidative stress in CKD stages 3-5 patients with HUA, thus reducing vascular endothelial injury. Elevated serum uric acid may be one of the important factors that promote oxidative stress and increase endothelial damage in CKD patients.
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OBJECTIVE： To systematically evaluate the efficacy and safety of febustrin （80 mg/d and 40 mg/d） and allopurinol （300 mg/d） in the treatment of gout， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Embase， Cochrane library， CJFD， Wanfang database and CBM during from database establishment to Mar. 2019， randomized controlled trial （RCT） about efficacy and safety of febustrin 80 mg/d （trial group）， 40 mg/d （observation group） and allopurinol 300 mg/d （control group） in the treatment of gout were collected. After extracting data of clinical studies met inclusion criteria and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was conducted for blood uric acid decrease level， the compliance rate of serum uric acid concentration， incidence of liver dysfunction， incidence of renal dysfunction， incidence of digestive tract reaction and frequency of acute gout attack with Rev Man 5.1 software and Stata 13.0 software. RESULTS： A total of 17 RCTs were included， involving 1 816 patients. Meta-analysis results showed that， the serum uric acid decrease level of patients in trial group [MD＝－70.17， 95％CI （－97.41， －42.93）， P＜0.001] and the compliance rate of serum uric acid concentration [RR＝1.58， 95％CI （1.20， 2.08）， P＝0.001] were higher than observation group； the decrease of serum uric acid level [MD＝－34.68，95％（－61.35， －8.00）， P＝0.01] and the compliance rate of serum uric acid concentration [RR＝1.39，95％CI（1.04，1.85）， P＝0.03] in trial group were significantly higher than control group； the frequency of acute gout attack [RR＝1.54（1.02，2.31）， P＝0.04] in trial group was significantly higher than observation group. The incidence of liver dysfunction in observation group [RR＝0.71，95％CI（0.52，0.99），P＝0.04] was significantly lower than control group， with statistical significance. There was no statistical significance in other indexes among other indexes （P＞0.05）. CONCLUSIONS： Compared with febulostat 40 mg/d and allopurinol 300 mg/d， the efficacy of febulostat 80 mg/d is superior in reducing uric acid levels of gout patients.
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Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease (CKD) stages 3-5 patients with hyperuricemia (HUA). Methods The study was a prospective cohort study. The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed. The patients were assigned to febuxostat (A) group, allopurinol (B) group and non -hyperuricemia (C) group according to the level of serum uric acid and the choice of urate-loweringdrugs. Serum uric acid, hypersensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and endothelin-1 (ET-1) were measured at baseline, 1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared. According to the level of serum uric acid, patients were divided into attainment group and nonattainment group, and the correlation between uric acid and oxidative stress was analyzed at baseline and 3 months after treatment respectively. Results There was no significant difference in baseline levels of serum uric acid, inflammation and oxidative stress between group A and group B (P>0.05). The levels of serum uric acid, hs-CRP, MDA and ET-1 of group A and group B were significantly higher than those of group C, but the level of SOD of group A and group B was significantly lower than that of group C at baseline (P<0.001). After treatment for 1 month and 3 months, the values of serum uric acid, hs-CRP, MDA and ET-1 in group A were significantly lower than those in group B, while the level of SOD in group A was significantly higher than that in group B (P<0.001). Compared with pre-treatment period, both the serum uric acid, hs-CRP, MDA and ET-1 levels of group A and group B were declined significantly while SOD had a significant rise after 3 months treatment (P<0.001). The changes of group A were significantly higher than those of group B (P<0.001). At baseline and 3 months after treatment, serum uric acid was positively related to hs-CRP, MDA and ET-1, but negatively related to SOD in nonattainment group (|r|>0.50, P<0.001);serum uric acid was positively related to hs-CRP, MDA and SOD (|r|>0.70, P<0.001), and there was no correlation between serum uric acid and ET-1 in attainment group (P>0.05). Conclusions Febuxostat performed better than allopurinol in lowering urate and inhibiting oxidative stress in CKD stages 3-5 patients with HUA, thus reducing vascular endothelial injury. Elevated serum uric acid may be one of the important factors that promote oxidative stress and increase endothelial damage in CKD patients.
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Objective:To prepare febuxostat nanosuspension and prepare sustained-release pellets,and investigate the in vitro dis-solution.Methods: Febuxostat nanosuspension was prepared by a high pressure homogenization method. Febuxostat nanosuspension pellets were prepared by fluidized bed coating technique. Eudragit RL30D and Eudragit RS30D were used to prepare the sustained-re-lease pellets. The dissolution mechanism of febuxostat nanosuspension sustained-release pellets was evaluated. Results: The average particle size of the prepared febuxostat nanosuspension was (212.5 ± 36.3) nm, PdI was (0.193 ± 0.018), zeta potential was ( -12.4 ± 0.3) mV,and the scanning electron microscopy showed that the particle size distribution of febuxostat nanosuspension was narrow. The in vitro dissolution of febuxostat nanosuspension sustained-release pellets was more stable and conformed to the first-order release model. Conclusion: The in vitro dissolution of febuxostat nanosuspension sustained-release pellets is more stable, and the preparation provides a new choice for febuxostat clinical application.
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Objective To investigate the clinical efficacy of heat-clearing and diuresis-promoting herbal formula Tongfeng Recipe in treating damp-turbidity-heat accumulation type of gout with tophus. Methods Sixty qualified patients were randomized into treatment group and control group, 30 cases in each group. The control group was given oral use of Febuxostat Tablets, and the treatment group was given Tongfeng Recipe combined with Febuxostat Tablets. After treatment for 6 months, we compared the changes of serum uric acid, the maximum diameter of the tophi, attack frequency of gout, scores of traditional Chinese medicine (TCM) syndromes, and adverse reaction in the two groups. Results (1) During the trial, 2 cases from the treatment group and 3 from the control group were lost to follow-up, and the final included case number of the treatment group and control group was 28, 27 respectively. (2) After treatment, the serum uric acid level in the two groups was decreased (P<0.01 compared with that before treatment), and the decrease in the treatment group was superior to that in the control group (P<0.05). (3) After treatment, the percentage of patients with serum uric acid less than 60mg/L in the treatment group and control group was 96.43％, 77.78％ respectively, the difference being significant(P<0.05).(4) After treatment, the maximum diameter of the tophi was reduced in the two groups(P<0.05 compared with that before treatment), and the decrease in the treatment group was superior to that in the control group (P<0.05). (5) After treatment, the scores of TCM syndromes in the two groups were markedly improved (P < 0.01 compared with those before treatment) , and the improvement in the treatment group was superior to that in the control group (P < 0.05). (6) During the treatment, acute attack of gout occurred in one case of the treatment group and in 7 cases of the control group, the difference being significant (P<0.05). The treatment group had 4 cases of diarrhea and one case of hepatic function injury, and the control group had 3 cases of diarrhea and one case of hepatic function injury , the difference being insignificant between the two groups (P > 0.05). Conclusion Heat-clearing and diuresis-promoting herbal formula Tongfeng Recipe exerts certain effect in treating damp-turbidity-heat accumulation type of gout with tophus, and the recipe is effective on decreasing serum uric acid, preventing the acute attack of gout induced by anti-uric acid treatment, and improving TCM syndromes.
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Objective@#To study the influence of allopurinol and febuxostat on IL-1β and NALP3 levels and liver and kidney function in gout patients with hyperuricemia.@*Methods@#A total of 108 patients with stable gout accompanied by hyperuricemia were selected and randomly divided into control group and observation group according to the digital table, with 54 cases in each group.The control group was given allopurinol 100mg/time, orally, 3 times/d.The observation group was given febuxostat 40mg/time, orally, 1 time/d.The two groups were treated 4 weeks for 1 course, continuous treatment for 6 courses.The contents of serum IL-1β and NALP3, and renal function[creatinine(Scr), urea nitrogen(BUN), glomerular filtration rate(GFR) and uric acid(UA)], liver function[alanine aminotransferase(ALT) and aspartate aminotransferase(AST)]of the two groups were detected, and the adverse reaction of the two groups were observed.@*Results@#After treatment, the contents of serum IL-1β and NALP3 of the observation group decreased gradually, which were lower than those of the control group(t=1.910, 2.196, 4.954, 1.732, 5.944, 7.935, all P<0.05). After treatment, the blood UA of the two groups decreased significantly, the blood UA of the observation group was lower than the control group(t=9.772, P<0.05). The other kidney function indicators had no statistically significant differences between the two groups (t=0.082, 0.923, 1.395, all P>0.05). The liver function indicators of the two groups had no statistically significant differences(t=0.860, 0.563, all P>0.05). The incidence rate of adverse reactions in the observation group was 5.77%, which was lower than 20.75% in the control group(χ2=5.101, P=0.024).@*Conclusion@#Febuxostat in the treatment of gout with hyperuricemia can effectively reduce the level of serum UA, and inhibit the expression of inflammatory factors such as IL-1β and NALP3, with high safety, which is worthy of clinical promotion.
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OBJECTIVE:To provide reference for optimizing gout drug therapy plan. METHODS:A total of 107 patients met gout clinical diagnosis criteria in the Affiliated Hospital of Putian University during Jul. 1st,2016- Jul. 1st,2017 were divided into group A and B according to carrying out HLA-B*58:01 gene detection or not. Group A was divided into positive and negative subgroup according to the results of gene detection. Positive subgroup was given febuxostat 40 mg,qd. Negative subgroup was given allopurinol 300 mg,tid with a treatment course for 2 weeks,the level of uric acid was detected after a treatment course;febuxostat was given instead if the level of uric acid was not up to the standard. Group B was given allopurinol;after a treatment course,the level of uric acid was detected;febuxostat was given instead (usage and dosage as group A) if the level of uric acid was not up to the standard. Both groups were treated for 6 months. The levels of uric acid were investigated in 2 groups before and after treatment so as to evaluate up-to-standard rate of treatment. European 5-D health scale of 2 groups were followed up with telephone to calculate therapeutic efficacy by QALY. Cost-effectiveness of 2 groups were calculated,and sensitivity analysis was conducted. RESULTS:Before treatment,there was no statistical significance in urine acid levels between 2 groups (P>0.05). After treatment,urine acid levels of 2 groups were significantly lower than before treatment with statistical significance(P<0.05). Therapeutic effectiveness was 0.818 QALY in group A and 0.808 QALY in group B,without statistical significance between 2 groups(P>0.05). The cost of group A was 3932.46 yuan,and that of group B was 2174.92 yuan. Cost-effectiveness ratio of 2 groups were 4807.41 and 2691.73,and group A was significantly higher than group B. The therapy plan of group B showed that cost-effectiveness advantage. Sensitivity analysis supported the results. There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:It shows cost-effectiveness advantage to directly use allopurinol without gene detection in gout patients.
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OBJECTIVE: To observe clinical efficacy and safety of febuxostat in the treatment of type 2 diabetic nephropathy complicated with hyperuricemia. METHODS: A total of 137 patients with type 2 diabetic nephropathy complicated with hyperuricemia selected from our hospital during Jan. 2014-Jun. 2016 were divided into group A (46 cases), B (47 cases), C (44 cases) according to random number table. On the basis of routine treatment, group A was given Allopurinol tablets orally with initial dose of 0. 05 g, bid; increasing to 0. 10 g, bid, 2 weeks later. Group B was given Benzbromarone tablets 50 mg orally, qd. Group C was given Febuxostat tablets orally with initial dose of 40 mg, qd; increasing to 80 mg, qd, 2 weeks later. All patients received treatment for consecutive 12 weeks. Clinical efficacies of 2 groups were observed, and the levels of serum uric acid (SUA), Scr and BUN were also observed before and after treatment. The occurrence of ADR was recorded. RESULTS: Four, six, three patients withdrew from the study in group A, B, C, respectively. The total response rates of group B, C (87. 8％, 85. 4％) were significantly higher than that of group A (76. 2％), with statistical significance (P＜0. 05); there was no statistical significance between group B and C (P＞0. 05). Before treatment, there was no statistical significance in the levels of SUA, Scr or BUN among 3 groups (P＞0. 05). Four weeks after treatment, the levels of SUA in 3 groups were decreased significantly compared to before treatment, with statistical significance (P＜0. 05); there was no statistical significance in other indexes among 3 groups or between before and after treatment (P＞0. 05). Twelve weeks after treatment, the levels of SUA in 3 groups were decreased significantly compared to before treatment and 4 weeks after treatment, and group B and C were significantly lower than group A; the levels of Scr in group A and C were decreased significantly compared to before treatment, while that of group B was increased significantly compared to before treatment and group B was significantly higher than group A and C, with statistical significance (P＜0. 05). There was no statistical significance in the levels of Scr or BUN among 3 groups compared to 4 weeks after treatment; there was also no statistical significance in the levels of SUA between group B and C, the levels of Scr between group A and C (P＞0. 05). Total incidence of ADR in group C (12. 20％) was significantly lower than group A and B (25. 58％, 24. 39％), with statistical significance (P＜0. 05); there was no statistical significance between group A and B (P＞0. 05). CONCLUSIONS: Febuxostat is better than allopurinol in reducing the level of SUA in type 2 diabetic nephropathy patients with hyperuricemia. It shows small effect on renal function with better safety.
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Objective To investigate the urate-lowering efficacy and renal effect of febuxostat in hyperuricemic patients with chronic kidney disease (CKD) stages 3-5. Methods A prospective, randomized, controlled trial of CKD stages 3-5 patients with hyperuricemia was conducted from June 2015 to June 2016. Patients were randomly assigned to either febuxostat group (treatment group) or allopurinol group (control group). Patients in treatment group received febuxostat 40 mg/d after study initiation, and the dosage was changed to 20 mg/d if serum uric acid (sUA)<360 μmol/L. Patients in control group were administered a dose of 100 mg/d of allopurinol. Serum uric acid, serum creatinine and other clinical parameters were measured at baseline and 1-6 months after treatment. The rate of achieving target sUA level and the change of eGFR in two groups were performed using SPSS 21.0. Results A total of 98 patients met the inclusion criteria and completed the trial. The treatment group and the control group had 51 cases and 47 cases, respectively. There was no significant difference between the two groups in age, sex, body mass index (BMI), blood pressure, serum creatinine, eGFR, sUA and renal diseases (P>0.05). At month 1-6, there were significant differences between treatment group and control group in the rate of achieving target sUA level (P<0.01). At month 1 and month 3, no statistical difference was observed in the change of eGFR between the two groups (P=0.624, P=0.319). At month 6, the changes in eGFR were +2.23 ml·min-1·(1.73 m2)-1 and-4.36 ml·min-1·(1.73 m2)-1 in the treatment and control group, respectively, and the difference between the two groups was significant (P=0.037). In patients with CKD stages 3-5, generalized estimating equation showed that after adjusting for confounding variables, the eGFR increased 1.149 ml·min-1·(1.73 m2)-1 (P=0.003) and 24-hour urinary protein decreased 0.019 g/d (P=0.037) when per 60 μmol/L decreased in sUA. Febuxostat 20 mg/d was able to keep target sUA levels in 90.2% patients with CKD stages 3-5 within half a year and no serious adverse effects appeared. Conclusions Febuxostat performs better than allopurinol in lowering urate and delaying progression of renal function in patients with CKD stages 3-5 and HUA. Febuxostat 20 mg/d may be the effective and safe maintenance dose to maintain target sUA level in patients with CKD stages 3-5, but whether it can be used as the best long-term maintenance dose needs to be further studied.
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Objective: To provide the methods and evidence for the treatment of patients with renal insufficiency and hyperuricemia, and explore the key points of work for clinical pharmacists.Methods: By participating in the treatment of one case of cervical cancer complicated with renal insufficiency and hyperuricemia, clinical pharmacist helped physician choose appropriate drugs and dosage, and monitored the patient with pharmaceutical care.Results: After the treatment, the blood uric acid decreased and renal function returned to normal, and the chemotherapy was completed successfully without obvious side effects.Conclusion: Clinical pharmacists participating in making individual therapeutic scheme can provide safe and effective medication care for patients and reduce adverse reactions.