Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology.

Gout is a metabolic arthritis caused by hyperuricemia. In recent years, the prevalence of gout has been increased significantly in China due to the improvement of the living standards, and gout has become another common metabolic disease following diabetes mellitus. Gout severely affects the health status and life quality of human. In order to monitor the near real-time prevalence of gout, a wastewater-based epidemiology (WBE) approach was carried out in 257 Chinese cities using febuxostat as the biomarker. Febuxostat in wastewater was measured by a LC-MS/MS method with satisfactory results of method validation. The average concentration of febuxostat in wastewater was 53.05 ± 31.76 ng/L, with the estimated per capita consumption of 124.40 ± 73.37 mg/day/1000 inhabitant. The calculated prevalence of febuxostat was 0.41 % ± 0.24 %, and the prevalence of gout was finally estimated to be 1.30 % ± 0.77 % (0.60 % to 2.11 %), which was nearly consistent with value of 1.10 % obtained from the Guideline for the diagnosis and management of hyperuricemia and gout in China (2019). The results indicated that the febuxostat-based WBE approach might be reasonable to assess the near real-time gout prevalence in China.

Comparison of the efficacy and safety of benzbromarone and febuxostat in gout and hyperuricemia: a systematic review and meta-analysis.

OBJECTIVE: Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood. This knowledge gap necessitates a comprehensive analysis and evidence update to guide drug selection for physicians and patients. METHOD: We conducted a systematic analysis by extracting relevant clinical studies from four medical literature databases. Forest plots, funnel plots, sensitivity analysis, Egger's test, and subgroup analysis were utilized to compare relevant indicators. RESULTS: The advantages and disadvantages of the two drugs were evaluated based on various indicators such as serum uric acid (SUA), triglyceride (TG), urinary uric acid (UUA), white blood cell count (WBC), total cholesterol (TC), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine (SC). Benzbromarone demonstrated better efficacy in rapidly reducing SUA levels and inhibiting inflammation for hyperuricemia and gout patients. Febuxostat was slightly less effective in lowering SUA, but there was no significant difference in its impact on liver and kidney function after long-term use. CONCLUSION: This study highlights the superiority of benzbromarone in rapidly reducing SUA and inhibiting inflammation. Febuxostat shows comparable effects on liver and kidney function after long-term use. These findings provide valuable insights for clinicians and patients in drug selection. Key Points • Benzbromarone stands out as a highly effective treatment for hyperuricemia and gout, offering rapid reduction of serum uric acid levels and potent anti-inflammatory effects. • When it comes to long-term use, febuxostat demonstrates comparable effects on liver and kidney function. This provides reassurance for patients who require extended treatment duration. • Moreover, our study goes beyond previous research by presenting a more comprehensive and detailed analysis.

Trends in healthcare utilization by patients with gout: A cross-sectional study using Health Insurance Review and Assessment Service data.

This study aimed to analyze the distribution of gout patients and the utilization of healthcare services in South Korea to provide valuable recommendations to clinicians and policymakers. A cross-sectional study was conducted. Claims data from the Health Insurance Review and Assessment Service spanning 2010 to 2019 were utilized, and a sample of 69,680 patients was included in the study. The incidence of gout was observed to be high in male patients over the age of 40, with most patients receiving outpatient care for gout management. Nonsteroidal anti-inflammatory drugs and urate-lowering agents were the most frequently prescribed medications, with prescriptions for colchicine and febuxostat increasing among urate-lowering agents. Musculoskeletal disorders were found to be the most common comorbidities among gout patients. Although the total costs of gout management increased, there was no significant increase in cost per patient. This study provides insights into the current state of healthcare utilization for gout patients in South Korea and trends in the disease burden and use of medications. The findings have crucial implications for clinicians and policymakers involved in decision-making regarding the management and treatment of gout.

Comparison of clinical and economic evaluation between selected generic and original febuxostat tablets in Chinese gout patients with hyperuricemia: A real-world multicenter retrospective study.

Generic febuxostat tablets were listed in China's third-round centralized drug procurement program. However, there are no sufficient data available on the use of febuxostat in a real-world setting. This study aimed to compare the efficacy, safety, and cost of selected generic febuxostat with original febuxostat in primary gout and hyperuricemia. Medical records at 3 tertiary hospitals from January 2014 to February 2022 were retrospectively analyzed. Propensity score matching was used to balance the distribution of baseline characteristics. The proportion of patients achieving target serum uric acid (SUA) levels at 12 weeks, the percent changes from baseline in SUA, adverse drug reactions, and the cost of febuxostat therapy were assessed. A total of 221 patients were recruited and 57 pairs of patients were 1:1 matched in the 2 groups. There was no statistically significant difference in the proportion of patients achieving a target SUA levels below 300 µmol/L, the percent changes of SUA decreased from baseline, and the incidence of adverse drug reactions between the 2 groups (all P > .05). The daily febuxostat cost in the generic group were significantly lower than that in original group (P < .05). Based on the results of this study, the clinical efficacy of selected generic febuxostat is comparable to that of original febuxostat for gout with hyperuricemia. No serious adverse reactions were reported in the 2 groups, and generic febuxostat is more economical than the original febuxostat.

Febuxostat dose requirement according to renal function in patients who achieve target serum urate levels: A retrospective cohort study.

OBJECTIVES: To determine the febuxostat dose requirement according to renal function in patients who achieve target serum urate (SU) levels. METHODS: Of 3153 gout patients who underwent febuxostat treatment, 873 patients with an initial SU level>6mg/dL were included and categorized by the estimated glomerular filtration rate: normal, chronic kidney disease (CKD) stage 3, and stages 4-5. Ninety-five patients with insufficient follow-up were further excluded. The dose of febuxostat in patients who achieved the SU target (< 6mg/dL) was defined as the average daily dosage at the time of SU target achievement. RESULTS: The cohort of 778 gout patients had a median age of 52.0 years (IQR, 41.0-63.0) and comprised 711 (91.4%) men. The mean SU at febuxostat initiation was higher in the CKD 4-5 (9.6 [± 3.1] mg/dL) than in the other groups (CKD 3, 8.7 [± 1.7]; normal, 8.4 [± 1.7]; P<0.001). Patients achieved target SU at a median of 4.0 (1.9-9.6) months and in those who achieved target SU, the dose of febuxostat at the time of SU target achievement was significantly lower in the CKD 4-5 group (50.0 [± 16.5] mg) than in the other groups (vs. CKD stage 3, 60.0 [± 19.5] mg; P<0.01, vs. normal, 60.0 [± 19.8] mg; P<0.01). Furthermore, CKD stage 4-5 had a negative correlation with the febuxostat dose requirement (Beta: -2.334, P<0.05). CONCLUSION: Among patients who achieved SU target, those with severely decreased renal function (CKD 4-5) required a lower febuxostat dose to achieve the target SU level compared to patients with normal or mild renal impairment.

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout.

BACKGROUND: While xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia. METHODS: A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12. RESULTS: Fewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target. CONCLUSIONS: People with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

Contributing Factors of Diabetes Mellitus among Patients with Gout (Results of the Long-Term Prospective Study).

It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age  ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m2; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m2; serum uric acid level (sUA) ≥ 420 µmol/L and  ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98-9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50-4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02-5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19-4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11-0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21-1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 µmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.

Febuxostat alleviates Arsenic Trioxide-Induced renal injury in Rats: Insights on the crosstalk between NLRP3/TLR4, Sirt-1/NF-κB/TGF-ß signaling Pathways, and miR-23b-3p, miR-181a-5b expression.

Febuxostat (FBX), a xanthine oxidase inhibitor, is known to improve renal function and can show promise as a therapeutic agent for preventing drug-induced nephrotoxicity. This study aimed to explore the protective effect of FBX in preventing renal damage caused by arsenic trioxide (ATO) toxicity and uncover the underlying mechanisms. The researchers examined how FBX (10 mg/kg, orally) affected ATO-induced kidney injury (5 mg/kg, intraperitoneally) in rats. Kidney function and toxicity parameters in serum and oxidative stress biomarkers and inflammatory cytokine levels in renal tissue were measured. H&E staining was used to detect histopathological changes in the kidney. Network the molecular mechanisms of FBX in improving kidney injury were investigated using Western blotting and PCR techniques. The findings showed that FBX improved kidney function by inhibiting the pathological changes seen in H&E staining, decreasing levels of probed kidney function and toxicity measures in serum and tissue, and exhibiting antioxidant and anti-inflammatory effects. FBX decreased MDA, MPO, TNF-α, IL-1ß, IL-6, COX-II, and NADPH oxidase levels, while increased GSH, GPx, SOD, and IL-10 levels. FBX also reduced the expression of NLRP3, ASC, TLR4, and micro-RNA 181a-5b while increased the expression of IKBα, Sirt-1, and micro-RNA 23b-3p, according to Western blotting and PCR results. In conclusion, FBX can play a vital role in reducing kidney injury in cases of ATO-induced nephrotoxicity, though more clinical research needs to be conducted.

Acute severe gouty arthritis secondary to isotretinoin toxicity in a young male: a case report.

Acute gouty arthritis is a recognized complication of hyperuricemia and one of the most common forms of inflammatory arthritis in adults. Drug-induced hyperuricemia is increasingly prevalent in clinical practice. Diuretics, antitubercular medications, and immunosuppressants are the common drugs associated with hyperuricemia. Oral isotretinoin is the drug of choice for different forms of severe acne and is rarely associated with hyperuricemia. We present the case of a 30-year-old male with severe acne vulgaris who was prescribed isotretinoin and later presented with acute gout. The patient developed hyperuricemia and swelling of the right first metatarsophalangeal joint within two months of isotretinoin commencement. There was a second episode of similar joint swelling three months later, parallel to the isotretinoin rechallenge. The dose of isotretinoin was reduced with the addition of febuxostat. The patient did not develop further episodes and remained symptom-free without urate-lowering therapy.

Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease.

Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Febuxostat administration significantly reduced the serum uric acid concentration among patients with CKD when compared with control [- 3.40 (95% CI - 4.19 to - 2.62) vs. - 0.35 (95% CI - 0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis among patients with decreased serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group showed significant difference at 8 weeks (2.01 (95% CI 0.31 to 3.7) vs. 0.04 (95% CI - 1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Febuxostat effectively reduced serum uric acid in the CKD population without improving endothelial dysfunction. It was able to preserve renal function in the subgroup of patients with CKD and lower serum uric acid level after treatment.Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005 .

Febuxostat, a xanthine oxidase inhibitor, regulated long noncoding RNAs and protected the brain after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease and is associated with a high global health burden. Long noncoding RNAs are involved in the pathological damage of ICH. Febuxostat, one of the xanthine oxidase inhibitors, is commonly used in the treatment of hyperuricemia and has been studied in different pathological processes, and its protective effects have been proven in different organs. This study was conducted to investigate whether febuxostat protects brain via regulating long noncoding RNAs after ICH. The modified neurological severity score, wire hanging test, Evans blue perfusion and immunofluorescence were performed to test the protective effects of febuxostat in a mouse model of ICH. Whole transcriptome sequencing was conducted to identify the lncRNAs affected by febuxostat and their functions were analyzed. Febuxostat ameliorated behavioral abnormalities and protected the blood-brain barrier after ICH. Fifteen lncRNAs regulated by febuxostat after ICH were detected. These 15 lncRNAs were associated with 83 gene ontology items. In total, 35 genes, 15 mRNAs and 202 miRNAs were regarded as potential targets for the 15 lncRNAs; 183 co-expressed genes were identified for these 15 lncRNAs and the co-expression network was constructed. Potential binding between lncRNAs and mRNAs was also studied. Enrichment analysis revealed that the functions of the 15 lncRNAs were related to maintaining the blood-brain barrier. This study demonstrated febuxostat protected brain after ICH. Fifteen lncRNAs were regulated and were associated with the effects of febuxostat on BBB integrity after ICH.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

INTRODUCTION: We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. METHODS: Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. RESULTS: This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). CONCLUSION: Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

[Prevention of urolithiasis using febuxostat in patients with metabolic syndrome].

INTRODUCTION: Urolithiasis is a chronic highly recurrent disease. The development of new methods of its pathogenetic treatment and prevention is a priority task of practical urology. AIM: To evaluate the clinical efficiency and safety of Febuxostat-SZ and to develop the rec-ommendations for its use in patients with uric acid stones. MATERIALS AND METHODS: The analysis of 525 patients with urolithiasis was carried out. On the basis of a comprehensive examination, they were divided into two groups: in the group 1, pa-tients (n=231) had urolithiasis and metabolic syndrome, while in the group 2 (n=294), only urolithia-sis was diagnosed without metabolic syndrome. In both groups, depending on the stone composi-tion, in addition to general measures, specific stone prevention was carried out, which included die-tary regimen and drug therapy. RESULTS: Uric acid excretion after 6 months of therapy in patients with urolithiasis and meta-bolic syndrome decreased from 9.8+/-1.8 to 3.9+/-1.1 mmol/l, urinary excretion of citrates and urine acidity increased from 0.8 +/-0.6 to 2.5+/-0.8 mmol/l and from 5.4+/-0.5 to 6.3+/-0.5, respectively, while serum uric acid level decreased from 451.4+/-15.1 up to 385.2+/-16.2 mmol/l. In the group of patients who, in addition to prescribing stone prevention, underwent correction of the metabolic syndrome, uric acid excretion after 3 months decreased by half: from 9.7+/-1.9 to 5.0+/-1.2 mmol/l, urine pH and citrate excretion increased from 5.4+/-0.4 to 6.3+/-0.5 and from 0.8+/-0.5 to 2.3+/-1.0 mmol/l, respective-ly, while serum uric acid level decreased from 459.5+/-17.7 to 370.9+/-15.1 mmol/l after 6 months of treatment. CONCLUSION: The use of Febuxostat-SZ in the complex therapy of urinary stone disease showed high efficiency in normalizing urine acidity, the level of daily excretion and serum uric acid level, as well as satisfactory tolerability and a minimal profile of side effects.

Association between urate-lowering therapy and cardiovascular events in patients with asymptomatic hyperuricemia.

INTRODUCTION/OBJECTIVES: To investigate the role of urate-lowering therapy (ULT) in the prevention of cardiovascular disease (CVD) in patients with asymptomatic hyperuricemia using the Japanese healthcare record database. METHODS: This retrospective cohort study used data from the JMDC Claims Database, which includes records of medical check-ups and Japanese health insurance claims. Subjects aged at least 18 years with a serum uric acid (sUA) level ≥ 7.0 mg/dL and at least one medical check-up from January 2007 to August 2021 were included in this study. The exposure was any ULT prescription, and the primary outcome included composite CVD outcomes, including coronary artery disease, stroke, and atrial fibrillation. Analysis was performed with a new-user design and overlap weighting to balance the baseline characteristics of the subjects. Cox proportional hazards models were used to investigate the association between ULT and the development of CVD. RESULTS: In total, 152,166 patients were included in the main analysis before overlap weighting in this retrospective cohort study. The number of subjects in the ULT group was 5,270, and there were 146,896 subjects in the control group. Composite CVD outcomes were observed in a total of 7,703 patients. The risk of developing composite CVD outcomes was not different between the ULT group and the control group (HR: 1.01, 95% CI: 0.89 to 1.13). CONCLUSIONS: ULT for patients with asymptomatic hyperuricemia did not prevent the development of CVD based on the Japanese claims database. Key points • Among subjects with asymptomatic hyperuricemia, ULT was not associated with a lower risk of CVD • There was no appropriate cutoff for initiating ULT in patients with asymptomatic hyperuricemia • There was no appropriate cutoff as the therapeutic goal of ULT in patients with asymptomatic hyperuricemia.

Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats.

BACKGROUND: Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats. METHODS: SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated. RESULTS: Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group. CONCLUSIONS: Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.

Comparison between the Effects of Allopurinol and Febuxostat on the Survival of Patients on Maintenance Hemodialysis.

INTRODUCTION: There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid-lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea. METHODS: This study used data from a national HD quality assessment program and the claims data. Use of ULDs was defined as more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups. Patients who were not prescribed allopurinol or febuxostat were included in group 1 (n = 43,251); patients who were prescribed allopurinol were included in group 2 (n = 9,987); and patients who were prescribed febuxostat were included in group 3 (n = 2,890). RESULTS: Kaplan-Meier curves showed that the survival rate was greatest in group 3 and worst in group 1 among the three groups. Multivariable analysis showed that group 2 had better patient survival compared to group 1; however, there was no significant difference in patient survival between groups 2 and 3. In addition, patients with hyperuricemia or gout had better patient survival compared to those without these diseases. CONCLUSIONS: Our study showed that survival in patients receiving ULDs was not inferior to that of those not receiving ULDs. Patient survival between patients on HD receiving allopurinol and those receiving febuxostat was similar.

Towards the Development of Dual Hypouricemic and Anti-inflammatory Candidates: Design, Synthesis, Stability Studies and Biological Evaluation of Some Mutual Ester Prodrugs of Febuxostat-NSAIDs.

Treatment of gout involves two basic approaches: reducing the serum uric acid mainly by xanthine oxidase inhibitors (XOIs) and alleviating the intensity of the accompanying acute arthritic inflammation using non-steroidal anti-inflammatory drugs (NSAIDs). Febuxostat (FEB) is the first non-purine XOI approved for the treatment of hyperuricemia and gout. The present study aims at combining the hypouricemic effect of FEB and the anti-inflammatory (AI) properties of NSAIDs in a single entity by adopting the "mutual prodrug" approach. Accordingly, a series of seven ester prodrugs comprising basically FEB together with different NSAIDs namely, diclofenac (4), ibuprofen (5), ketoprofen (6), indomethacin (7), naproxen (8), ketorolac (9) and etodolac (10) was synthesized. All the investigated seven prodrugs (4-10) were equipotent or even superior to their corresponding parent drugs in the hypouricemic and AI activities, together with a gastrointestinal (GI) safety profile. Among this series, the prodrug FEB-DIC (4) showed excellent dual in vivo hypouricemic and anti-inflammatory activity (43.60 % and 15.96 %, respectively) when compared to the parent drugs FEB and diclofenac (36.82 % and 12.10 %, respectively) and its physical mixture (37.28 % and 12.41 %, respectively). Investigation of the in vitro chemical stability and hydrolysis of the prodrug (4) in aqueous and biological samples using a developed HPLC method confirmed its stability in various pHs, whereas rapid hydrolysis to the parent drugs in liver homogenate and human plasma was proven. Finally, it is concluded that the mutual prodrug approach could be successfully used in drug design and development for overcoming undesirable difficulties without losing the desired activities of the parent drugs.

Renoprotective effect of febuxostat on contrast-induced acute kidney injury in chronic kidney disease patients stage 3: randomized controlled trial.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is known to be a complication of using intravascular contrast injection. Unfortunately, it is associated with adverse outcomes such as prolonged length of hospitalization and increased burden of health care costs. So, we aimed to determine the efficacy of febuxostat in the prevention of contrast-induced acute kidney injury among patients with chronic kidney disease Stage 3 performing percutaneous coronary intervention (PCI). METHODS: In a randomized controlled trial we enrolled 120 CKD stage 3 Patients with acute coronary syndrome referred to the cardiology department Ain-Shams University hospital for performing PCI and stenting. Patients were randomly assigned to two arms: Group I (study group): Included 60 patients who received Febuxostat added to the traditional treatment (IV hydration and N-acetylcysteine). The patients received Feburic 80 mg within 6-18 h before and within 6-18 h after the coronary intervention (a time gap of 24 h between two doses). Group II (control group): included 60 patients who received only traditional treatment. RESULTS: The incidence of AKI was higher in the control group with a statistically significant difference. We found that Independent Significant risk factors that led to AKI were febuxostate avoidance, DM, high urea level, high creatinine level, CKD stage 3B, high Mehran score and high AKI risk. CONCLUSION: We demonstrated that febuxostat has a Reno protective effect and it can help to reduce the incidence CI-AKI in CKD patients stage 3 performing PCI.

Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study.

BACKGROUND: Febuxostat is a selective xanthine oxidase inhibitor that reportedly exhibits antioxidant properties. We previously performed a multicentre, randomized controlled (PRIZE) study for vascular evaluation under uric acid (UA) control by febuxostat to investigate the progression of carotid lesions in asymptomatic hyperuricemic patients with carotid atherosclerosis for 2 years. HYPOTHESIS: The current subanalysis of the PRIZE study aimed to assess the effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker. METHODS: We recruited 383 patients (febuxostat group, n = 200; control group, n = 183) from the PRIZE trial for whom MDA-LDL measurements were available. The UA, MDA-LDL, low-density lipoprotein cholesterol (LDL-C) levels, and MDA-LDL/LDL-C ratio were identified, represented as the estimated difference from baseline to 24 months. We also evaluated the relationship between febuxostat dose (10, ≤20 to <40, and ≤40 to ≤60 mg) and changes in the MDA-LDL level, LDL-C level, or MDA-LDL/LDL-C ratios. RESULTS: The estimated change in MDA-LDL/LDL-C ratio from baseline to 24 months was significantly lower in the febuxostat group than in the control group (p = .025), whereas the estimated changes in MDA-LDL (p = .235) and LDL-C (p = .323) levels did not differ between the two groups. No significant correlation existed between the febuxostat doses and the estimated change in the MDA-LDL level (p = .626), LDL-C level (p = .896), or MDA-LDL/LDL-C ratio (p = .747). CONCLUSIONS: Our findings may indicate a possibility that febuxostat can lower the MDA-LDL/LDL-C ratio, a potential marker of atherosclerosis and oxidative stress, in asymptomatic hyperuricemic patients with carotid atherosclerosis. Further studies are required to validate our findings and elucidate the clinical antioxidant effect of febuxostat.