Febuxostat efficiently reduces the progression of chronic kidney disease in asymptomatic hyperuricemia: An interventional study

Febuxostat efficiently reduces the progression of chronic kidney disease in asymptomatic hyperuricemia: An interventional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Febuxostat efficiently reduces the progression of chronic kidney disease in asymptomatic hyperuricemia: An interventional study Showkat Azad, Pradip Kumar Dutta, Md Nurul Huda, Mohammad Abdul Kader, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5905053/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Therapeutic approaches for addressing asymptomatic chronic kidney disease (CKD) with renal impairment requires careful consideration, as there is a lack of substantial evidence endorsing specific medications. This study examined the outcomes of administering febuxostat to persons diagnosed with asymptomatic hyperuricemia in CKD (stages 3 and 4). Methods A single-patient blinded; placebo-controlled study was carried out at Chittagong Medical College Hospital in Chattogram 4203 over a one-year period. Participants were randomly assigned to two groups: one group received a daily dose of 40 mg of febuxostat while the other was given placebo tablets. As necessary, diuretics, antihypertensives, and antidiabetics were administered. Evaluations, which included patient history, physical examinations, outcomes, and pertinent tests, were performed at baseline, the 3rd month, and the 6th month. Results There were 105 similar-baseline patients in each group. The mean serum uric acid (SUA) level in the febuxostat group lowered from 8.55 to 4.92 mg/dL after six months, while in the placebo control it elevated from 8.10 to 8.99. In febuxostat group, the mean eGFR elevated from 25.28 to 27.01 ml/min/1.73 m 2 , while in the placebo control it reduced from 26.81 to 23.32. In the febuxostat group, at the six-month mark, eGFR differed across groups following a substantial decrease in systolic and diastolic blood pressure ( p < 0.05). Conclusions In our clinical setting, febuxostat proved more effective than a placebo in reducing serum uric acid levels and maintaining eGFR in patients with stage 3 and 4 CKD. Hence, febuxostat could be employed to treat hyperuricemia-associated asymptomatic chronic renal disease. Asymptomatic hyperuricemia CKD eGFR Febuxostat Serum uric acid Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Background Chronic Kidney Disease (CKD) is a medical state characterized by a continuous and irreversible deterioration in kidney function. The progression of CKD can vary depending on the underlying causes and the effectiveness of treatments, which typically involve the management of diabetes mellitus, hypertension, and proteinuria. Research has highlighted a link between high serum uric acid (SUA) levels and negative outcomes in those with CKD, suggesting that increased uric acid may play a role in the disease's progression and intensity 1 . Previous studies have demonstrated that males aged 30 to 40 exhibit a higher incidence of hyperuricemia (21.5%) 2 and its correlation with accelerated glomerular filtration rate (eGFR) decline 3 . According to Neogi T, hyperuricemia can lead to urate deposition diseases, attributed to the accumulation of monosodium urate monohydrate crystals within the extracellular fluids 4 . Iseki, K. et al . revealed that women who have a SUA level of 6.0 mg/dL, below the commonly established threshold for hyperuricemia 1 , are at a heightened risk of experiencing a downturn in renal function. Furthermore, hyperuricemia impacts the initiation of kidney impairment during the early phase of CKD 5 . For individuals with gouty arthritis or tophi, it is advisable to consider medications using urate-lowering drugs to manage hyperuricemia 6 . Alongside, it is recommended to provide lifestyle guidance encompassing dietary adjustments, drinking restrictions, physical exercise, education, and the management of concurrent health conditions. Febuxostat is a non-purine, non-competitive inhibitor of xanthine oxidase (XO). Unlike allopurinol, which is a purine-based inhibitor, febuxostat lacks a purine core structure and specifically inhibits both the oxidized and reduced forms of XO. It undergoes hepatic glucuronidation and oxidation for metabolism following excreted through both urinary and faecal pathways (49.1% and 44.9% excretion rates, respectively) 7 . Moreover, evidence supports the efficacy and favorable tolerability of this medication among individuals with slight to intermediate renal impairment 8 . Following treatment with oral febuxostat for five years in 116 hyperuricemic gout patients, a post hoc study demonstrated that urate lowering either maintained or improved eGFR 9 . The hypothesis posits that the decline of uric acid levels in the bloodstream may serve as a preventive measure toward the gradual loss of kidney function observed in individuals suffering from hyperuricemia and/or gout. It is absolutely necessary to conduct prospective studies in hyperuricemic individuals who already have compromised renal function to investigate the impact of reducing serum uric acid levels on renal function. The goal of this study was to assess the effectiveness of febuxostat in averting the deterioration of renal function, as reflected by estimated glomerular filtration rate (eGFR), in individuals with asymptomatic hyperuricemia who are in stages 3 and 4 of chronic kidney disease. Since uric acid has emerged as an open threat for CKD advancement, treating hyperuricemia, even in asymptomatic patients, with the cost-effective febuxostat could potentially halt the advancement of chronic kidney disease (CKD) and alleviate the burden on individuals who are prone to developing end-stage renal disease (ESRD). Considering the facts mentioned above and the limited number of experimental studies or research conducted in our country, further investigation is necessary. In this study we sought to appraise the effectiveness of febuxostat in ameliorating the advancement of chronic kidney disease (specifically stages 3 and 4) in individuals diagnosed with asymptomatic hyperuricemia. 2. Methods A quasi-experimental study was conducted at the Department of Nephrology in Chittagong Medical College Hospital, Chattogram 4203, Bangladesh from August 1, 2018 to March 30, 2019. It included 210 patients with confirmed chronic kidney disease (CKD) in stages 3 and 4, who exhibited asymptomatic hyperuricemia and were undergoing outpatient or inpatient treatment. The research methodology included a placebo control group to assess the efficacy of the intervention. 2.1 Inclusion and Exclusion criteria This study analyzed CKD patients at stages 3 and 4 with asymptomatic hyperuricemia, based on specific criteria. The study included participants aged 18 years or older with a serum uric acid level of 7 to 10.0 mg/dL and an eGFR range of 15–59 mL/min/1.73 m 3 . The study excluded kidney patients with uncontrolled diabetes mellitus, systolic blood pressure (SBP) above 140 mmHg, signs and symptoms of gout and urolithiasis, elevated liver enzymes, acute renal injury, severe heart failure, decompensated liver failure, active malignant disease, and a previous history of hypersensitivity to febuxostat. To ensure accuracy, individuals who had ingested allopurinol or febuxostat within five days prior to eligibility confirmation were also excluded. These criteria and exclusions aimed to focus the analysis on the specific population of interest and minimize confounding factors that could influence outcomes. 2.2 Procedure of the study For this interventional research, we looked at medical data for all ESRD patients admitted to the Nephrology ward at Chittagong Medical College Hospital, Chattogram 4203 between July 1, 2021, and June 30, 2022. Individuals in CKD stages 3 and 4 with blood uric acid levels between 7 and 10 mg/dL but no signs of hyperuricemia were chosen systematically. A standard case record form was used for data collection. Eligible participants were followed up every three months using medical history, physical parameters, and relevant investigations. Blood was obtained from an accessible vein in a red-topped vacutainer after the patient fasted for at least 4 hours/overnight. Serum uric acid, parathyroid hormone, creatinine, phosphate, calcium, and sGPT serum albumin were analyzed an automated bioanalyzer (HUMAN) to test serological parameters according to GmBH-Germany guidelines. HbA1c was tested using an automated analyzer in a blue-topped vacutainer without anticoagulant. Clinical condition and investigation reveal titrated medication dosage. Finally, 105 patients from each group were followed up. 2.3 Data Processing and Analysis : Data was checked and fed into SPSS or Graph Pad Prism for processing and assessment. Categorical variables were displayed in terms of both counts and percentages. For group comparisons, independent sample t-tests were used, and for comparisons within groups, we used paired sample t-tests. Correlations were determined with the use of Pearson's correlation test. A 95% confidence range was calculated and a significance level of p = 0.05 was employed. No adjustments were made to the provided p-values. 2.4 Flow Chart of the Study: 3. Results The study analyzed 210 CKD patients who participated in a placebo-controlled clinical study, taking into account their age, gender, comorbid conditions, serum uric acid, creatinine, and eGFR. The mean ages of the study group and controls were 48.97 (± 12.22) and 51.19 (± 7.19) years, respectively as shown in Table 1 (p = 0.215). The male gender accounted for 61.42% of the 210 CKD patients, with a p-value of 0.54. Additionally, 50% were diabetic and 90% were hypertensive, with either low literacy levels or having completed only elementary school. The observed difference achieved statistical significance at a level of p = 0.001. No discernable distinction in marital status was evident between the patients and controls. Mean eGFR values were 38.6 ± 11.4 and 78.3 ± 10.3 ml/min/1.73 m 2 for the CKD and control groups, respectively. Baseline data (Table I) showed no substantial disparity between the Febuxostat and Placebo groups. The Febuxostat group had an average age of 48.97 years, while the Placebo group had an average age of 51.97 years. In both categories, males made up the vast majority. The majority of individuals in the research had hypertension and/or diabetes. In both groups, about half of patients had these conditions, and their prevalence was similar at baseline (p > 0.05; Table 1). However, the difference observed between the two groups did not reach statistical significance (p > 0.05) and stage 4 CKD was more prevalent than stage 3 in both. In our research, there were no significant differences (p > 0.05) in systolic and diastolic blood pressure (DBP), serum creatinine, estimated glomerular filtration rate, and uric acid levels between the Febuxostat and Placebo groups. Both groups had similar uric acid levels at the baseline of the study. The febuxostat group exhibited a noteworthy decrease in serum uric acid levels compared to the placebo group at both 3 and 6 months (p < 0.001). As can be seen in Fig. 1 A and Table II, this pattern persisted throughout the investigation. Serum creatinine and eGFR comparison study between groups has shown a downward pattern of serum creatinine and an upsurge of eGFR in febuxostat group, whereas in placebo group was observed vice versa, the differences reached statistical significance at the final follow up (after 6 months) (Table III). After the 6-month course of febuxostat treatment, the serum creatinine levels showed a reduction, and the eGFR showed an increase compared to the baseline. However, statistical analysis indicated that this change was not significant (refer to Fig. 1 B and Table III). Meanwhile, the placebo group had a marked enhancement in serum creatinine levels and a reduction in eGFR after 6 months of treatment in comparison with the baseline (refer to Fig. 1 B and Table III). In the febuxostat group, 42 of 105 participants (40%) had an eGFR decrease of 10% compared with 66 of 105 participants (62.9%) in the placebo group. However, statistical significance wasn't achieved for this difference ( p = 0.085, Table IV). Diastolic and systolic blood pressures were compared at baseline, three months, and six months in Table II. After six months, febuxostat treated patients had lower systolic (Fig. 2 A) and diastolic (Fig. 2 B) blood pressure than those who took a placebo, with a p-value of 0.05 signifying statistical significance. The study identified a positive interrelation between the reduction of serum uric acid level and the reduction of both SBP (p = 0.047; Fig. 3 A) and DBP (p = 0.216; Fig. 3 B) in 6 months among the study subjects, with only the reduction of SBP being statistically significant. 4. Discussion Febuxostat, a non-purine selective xanthine oxidase inhibitor, effectively reduce SUA by inhibiting the enzymatic conversion of hypoxanthine and xanthine to uric acid 10 . Its hepatic metabolism and minimal renal clearance render it particularly suitable for patients with CKD, where renal excretion is compromised 11 , 12 . Hyperuricemia, a key factor in CKD progression, exacerbates renal dysfunction through inflammatory pathways, endothelial damage, and oxidative stress 13 , 14 . The findings of this study affirm febuxostat's efficacy in lowering serum urate levels in CKD patients, consistent with the results of Sircar et al. 15 and Akimoto et al. 16 , which documented sustained uric acid reductions with febuxostat therapy. However, despite these promising results, the role of febuxostat in modifying CKD progression remains controversial due to discrepancies across longitudinal studies and randomized controlled trials. Notably, the FEATHER trial 17 failed to demonstrate a significant impact of febuxostat on renal outcomes in CKD patients, suggesting that urate-lowering therapy alone may not be sufficient to influence disease progression. One of the most notable observations in this study is the trend toward stabilization of estimated glomerular filtration rate (eGFR) in the febuxostat-treated group compared to the placebo group. While this finding hints at a potential renoprotective effect, the absence of statistical significance diminishes its clinical relevance. This aligns with previous meta-analyses, such as the study by Liu X, et al.; which questioned the effectiveness of uric acid-lowering therapies in altering CKD progression 18 . The lack of a definitive renoprotective benefit may be attributed to confounding factors, including patient adherence variability, baseline comorbidities, and the study’s relatively short follow-up period. Furthermore, the observed reduction in serum creatinine levels in the febuxostat group lacked statistical significance, further complicating its potential role in renal preservation. Another critical finding is the significant reduction in systolic blood pressure among febuxostat-treated patients, consistent with results reported by Sarvepalli et al. 19 The underlying mechanism remains speculative, though it is hypothesized that febuxostat-mediated reductions in uric acid levels may enhance endothelial function and decrease vascular resistance. Nonetheless, contrasting evidence exists; several studies reported that the blood pressure-lowering effect of urate reduction may not be universal and could depend on additional metabolic and vascular factors 20 , 21 . Given the well-established link between hypertension and CKD progression, the observed decrease in blood pressure may confer indirect renal benefits. However, the long-term impact of febuxostat on blood pressure regulation warrants further validation through larger and more extended studies. The cardiovascular and renal safety of febuxostat remains debated. The CARES trial 22 reported increased cardiovascular mortality, while the FAST trial 23 , 24 suggested neutral risk in lower-risk populations but raised concerns for high-risk groups. CKD patients, already predisposed to cardiovascular complications due to systemic inflammation 25 and oxidative stress 26 may be particularly vulnerable. While febuxostat effectively lowers uric acid, its cardiovascular impact remains unclear, with evidence suggesting both prothrombotic and anti-inflammatory effects 22 . Similarly, its renal safety is contested, with studies linking febuxostat to acute kidney injury via oxidative stress 27 while others suggest potential renoprotective 28 benefits in CKD by improving endothelial function and reducing urate burden. In our study, no significant renal complications were observed, likely due to study limitations, including sample size, follow-up duration, and the absence of a high-risk CKD cohort. However, given the reported risks, future research must incorporate rigorous, long-term cardiovascular and renal monitoring to refine febuxostat’s risk-benefit profile. Notably, while hyperuricemia is associated with renal dysfunction, excessively low uric acid levels may impair nitric oxide synthesis and disrupt vascular homeostasis, potentially exacerbating renal and cardiovascular outcomes. This underscores the need for a balanced approach to uric acid management rather than aggressive reduction. Until conclusive data emerges, clinicians must exercise caution, ensuring individualized patient selection and thorough risk assessment. Our study suggests that while febuxostat effectively reduces serum uric acid levels, its impact on kidney function, as measured by eGFR and serum creatinine, remains inconclusive. Although a trend toward eGFR stabilization was observed in the febuxostat group, the lack of statistical significance limits the interpretation of a renoprotective effect. These findings align with previous research questioning the clinical benefits of uric acid-lowering therapies in CKD. Despite these insights, several limitations must be acknowledged. The relatively short follow-up period and modest sample size may have reduced the statistical power to detect significant changes in kidney function parameters. Additionally, as a single-center study conducted in a tertiary care hospital, the findings may not be generalizable to the broader CKD population. The absence of long-term cardiovascular and mortality outcomes further constrains definitive conclusions regarding febuxostat’s overall safety. Future research should prioritize large-scale, multicenter trials with longer follow-up durations and comprehensive renal and cardiovascular assessments to establish a clearer risk-benefit profile. Conclusion In conclusion, this study provides compelling evidence that febuxostat significantly lowers serum uric acid levels and reduces systolic blood pressure in CKD patients, highlighting its potential as a therapeutic option for this high-risk population. However, its effect on renal function remains uncertain, necessitating further investigation. These findings underscore the complex interplay between uric acid metabolism, kidney function, blood pressure regulation, and cardiovascular health. To establish febuxostat’s long-term safety and therapeutic value in CKD management, future studies must adopt a rigorous, multicenter approach with large sample size and extended follow-up, ensuring a comprehensive evaluation of both renal and cardiovascular outcomes in diverse patient cohorts. Abbreviations Chittagong Medical College and Hospital (CMCH) Chronic Kidney Disease (CKD) Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) End-stage renal disease (ESRD) estimated glomerular filtration rate (eGFR) Febuxostat versus Allopurinol Streamlined Trial (FAST) FEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER) serum uric acid (SUA) Statistical Package for Social Sciences (SPSS) xanthine oxidase (XO) Declarations Ethics approval and consent to participate: The Chittagong Medical College and Hospital Ethical and Review Committee authorized the study (CMC/PG/2021/488). Patients or their guardians gave their written consent after receiving necessary information. The confidentiality and identity of the patients were protected at all costs. Consent for publication: Not applicable Conflict of interest: The authors have no conflict of interest. Availability of data and material: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding: Not applicable Clinical trial number: Not applicable Acknowledgement: We would like to thank all the members of Medicine and Pediatric Department, Chittagong Medical College and Hospital, Chattogram 4203, Bangladesh, for their cordial support. References Iseki, K. et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. American journal of kidney diseases : the official journal of the National Kidney Foundation 44 , 642-650 (2004). Yamanaka, H. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides, nucleotides & nucleic acids 30 , 1018-1029, doi:10.1080/15257770.2011.596496 (2011). Satirapoj, B. et al. 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Tables Table I: Demographics and CKD stage of the study population by their treatment group ( n =210) Characteristics Febuxostat Group ( n =105) Placebo Group ( n =105) P value Age (years) Mean (±SD) 48.97 (±12.22) 51.97 (±7.19) 0.215* Range 19-75 38-63 Sex Male 57 (54.3%) 72 (68.6%) 0.220 † Female 48 (45.7%) 33 (31.4%) Creatinine Unit (mg/dL) 2.70±0.63 2.54±0.50 0.251* eGFR Unit (ml/min per 1.73 m 2 ) 25.28±7.59 26.81±7.31 0.392* Uric acid Unit (mg/dL) 8.55±1.05 8.10±0.61 0.054* H/O HTN Yes 90 (85.7%) 99 (94.3%) 0.232 † No 15 (14.3%) 6 (5.7%) H/O DM Yes 54 (51.4%) 51 (48.6%) 0.821 † Yes 54 (51.4%) 51 (48.6%) CKD stage Stage 3 36 (34.3%) 30 (28.6%) 0.607 † Stage 4 69 (65.7%) 75 (71.4%) BP (mmHg) Mean (±SD) Systolic BP 137±7 138±8 0.660* Diastolic BP 86±8 84±8 0.250* H/O: Signifies a history of; HTN: Hypertension; DM: Diabetes mellitus; BP: Blood Pressure. Unless specified otherwise, the data are presented as frequencies (in percentages); SD: Standard Deviation. *The P-value was computed through an independent sample t-test. † : P value was obtained through a chi -square test. Table II: Comparison of serum uric acid, serum creatinine, eGFR, systolic BP and diastolic BP between groups during the study period Parameters (unit) Time interval Study Groups N Mean ± SD P value † Serum uric acid (mg/dL) Baseline Febuxostat 105 8.55±1.05 0.054 Placebo 105 8.10±0.6 Month 3 Febuxostat 105 6.01±0.89 <0.001 Placebo 105 8.41±0.70 Month 6 Febuxostat 105 4.92±0.64 <0.001 Placebo 105 8.99±0.27 Serum creatinine (mg/dL) Baseline Febuxostat 105 2.70±0.63 0.251 Placebo 105 2.54±0.50 Month 3 Febuxostat 105 2.55±0.73 0.313 Placebo 105 2.72±0.63 Month 6 Febuxostat 105 2.45±0.88 0.019 Placebo 105 3.03±1.15 eGFR (ml/min/1.73 m 2 ) Baseline Febuxostat 105 25.28±7.59 0.329 Placebo 105 26.81±7.31 Month 3 Febuxostat 105 26.08±7.84 0.671 Placebo 105 25.31±7.15 Month 6 Febuxostat 105 27.01±8.29 0.048 Placebo 105 23.32±7.72 Systolic Blood Pressure (SBP) Baseline Febuxostat 105 137±7 0.680 Placebo 105 138±8 Month 3 Febuxostat 105 131±7 0.058 Placebo 105 135±7 Month 6 Febuxostat 105 130±8 0.023 Placebo 105 134±7 Diastolic Blood Pressure (DBP) Baseline Febuxostat 105 86±8 0.250 Placebo 105 84±8 Month 3 Febuxostat 105 78±6 0.058 Placebo 105 76±5 Month 6 Febuxostat 105 76±6 0.025 Placebo 105 80±7 † P values were derived from independent sample t test; BP: Blood pressure Table III: Changes in serum creatinine and eGFR from baseline from baseline to month 6 in the study groups Study group Variables (unit) Mean (±SD) values P value † At Baseline At month 6 Febuxostat Serum creatinine (mg/dL) 2.70±0.63 2.45±0.88 0.092 eGFR (ml/min per 1.73 m 2 ) 25.28±7.59 27.01±8.29 0.164 Placebo Serum creatinine (mg/dL) 2.54±0.50 3.03±1.5 0.003 eGFR (ml/min per 1.73 m 2 ) 26.81±7.31 23.32±7.72 <0.001 CI: Confidence interval; † P values are derived through a paired sample t test. Table IV: Percentage of patients experiencing a 10% reduction in eGFR at baseline eGFR change category Febuxostat group (n=105) Placebo group (n=105) P value* Decline ≥10% of baseline 42 (40.0%) 66 (62.9%) Decline <10% of baseline 9 (8.6%) 12 (11.4%) 0.085 No change or improvement 54 (51.4%) 27 (25.7%) *P value was derived from Chi -square test. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Apr, 2025 Reviews received at journal 05 Apr, 2025 Reviewers agreed at journal 05 Apr, 2025 Reviewers agreed at journal 04 Apr, 2025 Reviewers invited by journal 04 Apr, 2025 Submission checks completed at journal 27 Mar, 2025 First submitted to journal 24 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Sujan Islam","email":"","orcid":"","institution":"Mawlana Bhashani Science and Technology University","correspondingAuthor":false,"prefix":"","firstName":"Md.","middleName":"Sujan","lastName":"Islam","suffix":""},{"id":438773856,"identity":"436c3ce8-e0fc-4cfc-b82f-05510381c3bc","order_by":10,"name":"Sadia Afrin","email":"","orcid":"","institution":"Mawlana Bhashani Science and Technology University","correspondingAuthor":false,"prefix":"","firstName":"Sadia","middleName":"","lastName":"Afrin","suffix":""},{"id":438773857,"identity":"b3de9caa-5f43-4a99-a539-637af9035ab8","order_by":11,"name":"Mohammed Mehadi Hassan Chowdhury","email":"","orcid":"","institution":"Noakhali Science and Technology University","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"Mehadi Hassan","lastName":"Chowdhury","suffix":""},{"id":438773858,"identity":"e976cc94-20d2-4c7a-b3aa-13a91a9c48c3","order_by":12,"name":"Subodh Kumar Sarkar","email":"","orcid":"","institution":"Noakhali Science and Technology University","correspondingAuthor":false,"prefix":"","firstName":"Subodh","middleName":"Kumar","lastName":"Sarkar","suffix":""},{"id":438773859,"identity":"024467ac-136a-4b12-9a8b-9bf28545eb2f","order_by":13,"name":"Ashekul Islam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYFACHgbGxgaGBH4gAy4iQZQWyQaglgMkaTE4QKwW/v6zBx/O3LEtz/ja2cOfP7YxyPM38B68gU+LxI28ZMONZ24Xm93OS5M42MZgOOMAX7IFXnfd4DGTfNh2O3Hb7RwzBqAWxg0MPGZ4HSZ//oz5T5CWzbNzjD8AtdgT1GJwIMeMcSNQywbpHAOQwxIJajG8kWMsORPoFwmQX86ck0iecZiAX+TOnzH82Lvjdh7/7NzDHyrKbGz723vxhxg6ADqJmRT1o2AUjIJRMAqwAgCUsFHoxDDuNAAAAABJRU5ErkJggg==","orcid":"","institution":"Mawlana Bhashani Science and Technology University","correspondingAuthor":true,"prefix":"","firstName":"Ashekul","middleName":"","lastName":"Islam","suffix":""}],"badges":[],"createdAt":"2025-01-26 07:38:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5905053/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5905053/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80046039,"identity":"8f4b7ffe-db76-416e-b21a-36b71d764a9a","added_by":"auto","created_at":"2025-04-07 09:47:58","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43014,"visible":true,"origin":"","legend":"\u003cp\u003eMarginal averages of serum uric acid levels (A) and eGFR (B) in both groups from baseline to 6 months\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5905053/v1/1d19d3506b242382f7aeb3e1.jpg"},{"id":80044533,"identity":"a2f6b665-f6c9-4b08-93ca-3311633ca91d","added_by":"auto","created_at":"2025-04-07 09:39:58","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":43062,"visible":true,"origin":"","legend":"\u003cp\u003eEstimated marginal means of SBP (A) and DBP (B) in both groups from baseline to 6 months\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5905053/v1/dba2c72ea3046548fd77e09b.jpg"},{"id":80046040,"identity":"65d05a08-55e0-4614-9b6c-31be7758a549","added_by":"auto","created_at":"2025-04-07 09:47:58","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":50439,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment-related reduction in uric acid and SBP (A) and DBP (B) among 210 CKD patients.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5905053/v1/53da0ec60f91e1135f04ce62.jpg"},{"id":80044536,"identity":"d671b02c-e2ac-479d-b4ed-4bf5d76f1287","added_by":"auto","created_at":"2025-04-07 09:39:58","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":94429,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Method section.\u003c/p\u003e","description":"","filename":"un1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5905053/v1/17b4de66717b526f307f7b2b.jpg"},{"id":80049458,"identity":"02bd0476-a8fd-4c4e-80c8-029194e75320","added_by":"auto","created_at":"2025-04-07 10:11:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1319740,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5905053/v1/d092d009-05f4-449d-b586-73442d8f119a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Febuxostat efficiently reduces the progression of chronic kidney disease in asymptomatic hyperuricemia: An interventional study","fulltext":[{"header":"1. Background","content":"\u003cp\u003eChronic Kidney Disease (CKD) is a medical state characterized by a continuous and irreversible deterioration in kidney function. The progression of CKD can vary depending on the underlying causes and the effectiveness of treatments, which typically involve the management of diabetes mellitus, hypertension, and proteinuria. Research has highlighted a link between high serum uric acid (SUA) levels and negative outcomes in those with CKD, suggesting that increased uric acid may play a role in the disease's progression and intensity\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Previous studies have demonstrated that males aged 30 to 40 exhibit a higher incidence of hyperuricemia (21.5%)\u003csup\u003e2\u003c/sup\u003e and its correlation with accelerated glomerular filtration rate (eGFR) decline\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. According to Neogi T, hyperuricemia can lead to urate deposition diseases, attributed to the accumulation of monosodium urate monohydrate crystals within the extracellular fluids\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Iseki, K. \u003cem\u003eet al\u003c/em\u003e. revealed that women who have a SUA level of 6.0 mg/dL, below the commonly established threshold for hyperuricemia\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, are at a heightened risk of experiencing a downturn in renal function. Furthermore, hyperuricemia impacts the initiation of kidney impairment during the early phase of CKD\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. For individuals with gouty arthritis or tophi, it is advisable to consider medications using urate-lowering drugs to manage hyperuricemia\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Alongside, it is recommended to provide lifestyle guidance encompassing dietary adjustments, drinking restrictions, physical exercise, education, and the management of concurrent health conditions.\u003c/p\u003e \u003cp\u003eFebuxostat is a non-purine, non-competitive inhibitor of xanthine oxidase (XO). Unlike allopurinol, which is a purine-based inhibitor, febuxostat lacks a purine core structure and specifically inhibits both the oxidized and reduced forms of XO. It undergoes hepatic glucuronidation and oxidation for metabolism following excreted through both urinary and faecal pathways (49.1% and 44.9% excretion rates, respectively)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Moreover, evidence supports the efficacy and favorable tolerability of this medication among individuals with slight to intermediate renal impairment \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Following treatment with oral febuxostat for five years in 116 hyperuricemic gout patients, a post hoc study demonstrated that urate lowering either maintained or improved eGFR \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The hypothesis posits that the decline of uric acid levels in the bloodstream may serve as a preventive measure toward the gradual loss of kidney function observed in individuals suffering from hyperuricemia and/or gout. It is absolutely necessary to conduct prospective studies in hyperuricemic individuals who already have compromised renal function to investigate the impact of reducing serum uric acid levels on renal function. The goal of this study was to assess the effectiveness of febuxostat in averting the deterioration of renal function, as reflected by estimated glomerular filtration rate (eGFR), in individuals with asymptomatic hyperuricemia who are in stages 3 and 4 of chronic kidney disease. Since uric acid has emerged as an open threat for CKD advancement, treating hyperuricemia, even in asymptomatic patients, with the cost-effective febuxostat could potentially halt the advancement of chronic kidney disease (CKD) and alleviate the burden on individuals who are prone to developing end-stage renal disease (ESRD). Considering the facts mentioned above and the limited number of experimental studies or research conducted in our country, further investigation is necessary. In this study we sought to appraise the effectiveness of febuxostat in ameliorating the advancement of chronic kidney disease (specifically stages 3 and 4) in individuals diagnosed with asymptomatic hyperuricemia.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eA quasi-experimental study was conducted at the Department of Nephrology in Chittagong Medical College Hospital, Chattogram 4203, Bangladesh from August 1, 2018 to March 30, 2019. It included 210 patients with confirmed chronic kidney disease (CKD) in stages 3 and 4, who exhibited asymptomatic hyperuricemia and were undergoing outpatient or inpatient treatment. The research methodology included a placebo control group to assess the efficacy of the intervention.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Inclusion and Exclusion criteria\u003c/h2\u003e \u003cp\u003eThis study analyzed CKD patients at stages 3 and 4 with asymptomatic hyperuricemia, based on specific criteria. The study included participants aged 18 years or older with a serum uric acid level of 7 to 10.0 mg/dL and an eGFR range of 15\u0026ndash;59 mL/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The study excluded kidney patients with uncontrolled diabetes mellitus, systolic blood pressure (SBP) above 140 mmHg, signs and symptoms of gout and urolithiasis, elevated liver enzymes, acute renal injury, severe heart failure, decompensated liver failure, active malignant disease, and a previous history of hypersensitivity to febuxostat. To ensure accuracy, individuals who had ingested allopurinol or febuxostat within five days prior to eligibility confirmation were also excluded. These criteria and exclusions aimed to focus the analysis on the specific population of interest and minimize confounding factors that could influence outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Procedure of the study\u003c/h2\u003e \u003cp\u003eFor this interventional research, we looked at medical data for all ESRD patients admitted to the Nephrology ward at Chittagong Medical College Hospital, Chattogram 4203 between July 1, 2021, and June 30, 2022. Individuals in CKD stages 3 and 4 with blood uric acid levels between 7 and 10 mg/dL but no signs of hyperuricemia were chosen systematically. A standard case record form was used for data collection. Eligible participants were followed up every three months using medical history, physical parameters, and relevant investigations. Blood was obtained from an accessible vein in a red-topped vacutainer after the patient fasted for at least 4 hours/overnight. Serum uric acid, parathyroid hormone, creatinine, phosphate, calcium, and sGPT serum albumin were analyzed an automated bioanalyzer (HUMAN) to test serological parameters according to GmBH-Germany guidelines. HbA1c was tested using an automated analyzer in a blue-topped vacutainer without anticoagulant. Clinical condition and investigation reveal titrated medication dosage. Finally, 105 patients from each group were followed up.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003e2.3 Data Processing and Analysis\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eData was checked and fed into SPSS or Graph Pad Prism for processing and assessment. Categorical variables were displayed in terms of both counts and percentages. For group comparisons, independent sample t-tests were used, and for comparisons within groups, we used paired sample t-tests. Correlations were determined with the use of Pearson's correlation test. A 95% confidence range was calculated and a significance level of p\u0026thinsp;=\u0026thinsp;0.05 was employed. No adjustments were made to the provided p-values.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\u003cp\u003e\u003cstrong\u003e2.4\u003c/strong\u003e \u003cstrong\u003eFlow Chart of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ethe\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Study:\u003c/strong\u003e\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe study analyzed 210 CKD patients who participated in a placebo-controlled clinical study, taking into account their age, gender, comorbid conditions, serum uric acid, creatinine, and eGFR. The mean ages of the study group and controls were 48.97 (\u0026plusmn;\u0026thinsp;12.22) and 51.19 (\u0026plusmn;\u0026thinsp;7.19) years, respectively as shown in Table\u0026nbsp;1 (p\u0026thinsp;=\u0026thinsp;0.215). The male gender accounted for 61.42% of the 210 CKD patients, with a p-value of 0.54. Additionally, 50% were diabetic and 90% were hypertensive, with either low literacy levels or having completed only elementary school. The observed difference achieved statistical significance at a level of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001. No discernable distinction in marital status was evident between the patients and controls. Mean eGFR values were 38.6\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4 and 78.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3 ml/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e for the CKD and control groups, respectively.\u003c/p\u003e \u003cp\u003eBaseline data (Table I) showed no substantial disparity between the Febuxostat and Placebo groups. The Febuxostat group had an average age of 48.97 years, while the Placebo group had an average age of 51.97 years. In both categories, males made up the vast majority.\u003c/p\u003e \u003cp\u003eThe majority of individuals in the research had hypertension and/or diabetes. In both groups, about half of patients had these conditions, and their prevalence was similar at baseline (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;1). However, the difference observed between the two groups did not reach statistical significance (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) and stage 4 CKD was more prevalent than stage 3 in both. In our research, there were no significant differences (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) in systolic and diastolic blood pressure (DBP), serum creatinine, estimated glomerular filtration rate, and uric acid levels between the Febuxostat and Placebo groups.\u003c/p\u003e \u003cp\u003eBoth groups had similar uric acid levels at the baseline of the study. The febuxostat group exhibited a noteworthy decrease in serum uric acid levels compared to the placebo group at both 3 and 6 months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As can be seen in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and Table II, this pattern persisted throughout the investigation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSerum creatinine and eGFR comparison study between groups has shown a downward pattern of serum creatinine and an upsurge of eGFR in febuxostat group, whereas in placebo group was observed vice versa, the differences reached statistical significance at the final follow up (after 6 months) (Table III).\u003c/p\u003e \u003cp\u003eAfter the 6-month course of febuxostat treatment, the serum creatinine levels showed a reduction, and the eGFR showed an increase compared to the baseline. However, statistical analysis indicated that this change was not significant (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB and Table III). Meanwhile, the placebo group had a marked enhancement in serum creatinine levels and a reduction in eGFR after 6 months of treatment in comparison with the baseline (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB and Table III).\u003c/p\u003e \u003cp\u003eIn the febuxostat group, 42 of 105 participants (40%) had an eGFR decrease of 10% compared with 66 of 105 participants (62.9%) in the placebo group. However, statistical significance wasn't achieved for this difference (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.085, Table IV).\u003c/p\u003e \u003cp\u003eDiastolic and systolic blood pressures were compared at baseline, three months, and six months in Table II. After six months, febuxostat treated patients had lower systolic (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) and diastolic (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) blood pressure than those who took a placebo, with a p-value of 0.05 signifying statistical significance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe study identified a positive interrelation between the reduction of serum uric acid level and the reduction of both SBP (p\u0026thinsp;=\u0026thinsp;0.047; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA) and DBP (p\u0026thinsp;=\u0026thinsp;0.216; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB) in 6 months among the study subjects, with only the reduction of SBP being statistically significant.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eFebuxostat, a non-purine selective xanthine oxidase inhibitor, effectively reduce SUA by inhibiting the enzymatic conversion of hypoxanthine and xanthine to uric acid\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Its hepatic metabolism and minimal renal clearance render it particularly suitable for patients with CKD, where renal excretion is compromised\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Hyperuricemia, a key factor in CKD progression, exacerbates renal dysfunction through inflammatory pathways, endothelial damage, and oxidative stress\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The findings of this study affirm febuxostat's efficacy in lowering serum urate levels in CKD patients, consistent with the results of Sircar et al.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e and Akimoto et al.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, which documented sustained uric acid reductions with febuxostat therapy. However, despite these promising results, the role of febuxostat in modifying CKD progression remains controversial due to discrepancies across longitudinal studies and randomized controlled trials. Notably, the FEATHER trial\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e failed to demonstrate a significant impact of febuxostat on renal outcomes in CKD patients, suggesting that urate-lowering therapy alone may not be sufficient to influence disease progression.\u003c/p\u003e \u003cp\u003eOne of the most notable observations in this study is the trend toward stabilization of estimated glomerular filtration rate (eGFR) in the febuxostat-treated group compared to the placebo group. While this finding hints at a potential renoprotective effect, the absence of statistical significance diminishes its clinical relevance. This aligns with previous meta-analyses, such as the study by Liu X, et al.; which questioned the effectiveness of uric acid-lowering therapies in altering CKD progression\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. The lack of a definitive renoprotective benefit may be attributed to confounding factors, including patient adherence variability, baseline comorbidities, and the study’s relatively short follow-up period. Furthermore, the observed reduction in serum creatinine levels in the febuxostat group lacked statistical significance, further complicating its potential role in renal preservation.\u003c/p\u003e \u003cp\u003eAnother critical finding is the significant reduction in systolic blood pressure among febuxostat-treated patients, consistent with results reported by Sarvepalli et al.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The underlying mechanism remains speculative, though it is hypothesized that febuxostat-mediated reductions in uric acid levels may enhance endothelial function and decrease vascular resistance. Nonetheless, contrasting evidence exists; several studies reported that the blood pressure-lowering effect of urate reduction may not be universal and could depend on additional metabolic and vascular factors\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Given the well-established link between hypertension and CKD progression, the observed decrease in blood pressure may confer indirect renal benefits. However, the long-term impact of febuxostat on blood pressure regulation warrants further validation through larger and more extended studies.\u003c/p\u003e \u003cp\u003eThe cardiovascular and renal safety of febuxostat remains debated. The CARES trial\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e reported increased cardiovascular mortality, while the FAST trial\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003esuggested neutral risk in lower-risk populations but raised concerns for high-risk groups. CKD patients, already predisposed to cardiovascular complications due to systemic inflammation\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e and oxidative stress\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e may be particularly vulnerable. While febuxostat effectively lowers uric acid, its cardiovascular impact remains unclear, with evidence suggesting both prothrombotic and anti-inflammatory effects\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Similarly, its renal safety is contested, with studies linking febuxostat to acute kidney injury via oxidative stress\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e while others suggest potential renoprotective\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e benefits in CKD by improving endothelial function and reducing urate burden. In our study, no significant renal complications were observed, likely due to study limitations, including sample size, follow-up duration, and the absence of a high-risk CKD cohort. However, given the reported risks, future research must incorporate rigorous, long-term cardiovascular and renal monitoring to refine febuxostat’s risk-benefit profile. Notably, while hyperuricemia is associated with renal dysfunction, excessively low uric acid levels may impair nitric oxide synthesis and disrupt vascular homeostasis, potentially exacerbating renal and cardiovascular outcomes. This underscores the need for a balanced approach to uric acid management rather than aggressive reduction. Until conclusive data emerges, clinicians must exercise caution, ensuring individualized patient selection and thorough risk assessment.\u003c/p\u003e \u003cp\u003eOur study suggests that while febuxostat effectively reduces serum uric acid levels, its impact on kidney function, as measured by eGFR and serum creatinine, remains inconclusive. Although a trend toward eGFR stabilization was observed in the febuxostat group, the lack of statistical significance limits the interpretation of a renoprotective effect. These findings align with previous research questioning the clinical benefits of uric acid-lowering therapies in CKD. Despite these insights, several limitations must be acknowledged. The relatively short follow-up period and modest sample size may have reduced the statistical power to detect significant changes in kidney function parameters. Additionally, as a single-center study conducted in a tertiary care hospital, the findings may not be generalizable to the broader CKD population. The absence of long-term cardiovascular and mortality outcomes further constrains definitive conclusions regarding febuxostat’s overall safety. Future research should prioritize large-scale, multicenter trials with longer follow-up durations and comprehensive renal and cardiovascular assessments to establish a clearer risk-benefit profile.\u003c/p\u003e "},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study provides compelling evidence that febuxostat significantly lowers serum uric acid levels and reduces systolic blood pressure in CKD patients, highlighting its potential as a therapeutic option for this high-risk population. However, its effect on renal function remains uncertain, necessitating further investigation. These findings underscore the complex interplay between uric acid metabolism, kidney function, blood pressure regulation, and cardiovascular health. To establish febuxostat’s long-term safety and therapeutic value in CKD management, future studies must adopt a rigorous, multicenter approach with large sample size and extended follow-up, ensuring a comprehensive evaluation of both renal and cardiovascular outcomes in diverse patient cohorts.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eChittagong Medical College and Hospital (CMCH)\u003c/p\u003e\n\u003cp\u003eChronic Kidney Disease (CKD)\u003c/p\u003e\n\u003cp\u003eCardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES)\u003c/p\u003e\n\u003cp\u003eEnd-stage renal disease (ESRD)\u003c/p\u003e\n\u003cp\u003eestimated glomerular filtration rate (eGFR)\u003c/p\u003e\n\u003cp\u003eFebuxostat versus Allopurinol Streamlined Trial (FAST)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFEbuxostat versus placebo rAndomized controlled Trial regarding reduced renal function in patients with Hyperuricemia complicated by chRonic kidney disease stage 3 (FEATHER) \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eserum uric acid (SUA)\u003c/p\u003e\n\u003cp\u003eStatistical Package for Social Sciences (SPSS)\u003c/p\u003e\n\u003cp\u003exanthine oxidase (XO) \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate:\u003c/em\u003e\u003c/strong\u003eThe Chittagong Medical College and Hospital Ethical and Review Committee authorized the study (CMC/PG/2021/488). Patients or their guardians gave their written consent after receiving necessary information. The confidentiality and identity of the patients were protected at all costs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflict of interest:\u003c/em\u003e\u003c/strong\u003e The authors have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and material:\u003c/em\u003e\u003c/strong\u003e The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding:\u003c/em\u003e\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical trial number:\u003c/em\u003e\u003c/strong\u003e Not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgement:\u003c/em\u003e\u003c/strong\u003eWe would like to thank all the members of Medicine and Pediatric Department, Chittagong Medical College and Hospital, Chattogram 4203, Bangladesh, for their cordial support.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIseki, K.\u003cem\u003e et al.\u003c/em\u003e Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. \u003cem\u003eAmerican journal of kidney diseases : the official journal of the National Kidney Foundation\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 642-650 (2004).\u003c/li\u003e\n\u003cli\u003eYamanaka, H. 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H.\u003cem\u003e et al.\u003c/em\u003e Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease. \u003cem\u003eMedical science monitor : international medical journal of experimental and clinical research\u003c/em\u003e \u003cstrong\u003e30\u003c/strong\u003e, e944314, doi:10.12659/msm.944314 (2024).\u003c/li\u003e\n\u003cli\u003eMackenzie, I. S.\u003cem\u003e et al.\u003c/em\u003e Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. \u003cem\u003eThe Lancet\u003c/em\u003e \u003cstrong\u003e396\u003c/strong\u003e, 1745-1757, doi:10.1016/S0140-6736(20)32234-0 (2020).\u003c/li\u003e\n\u003cli\u003eRapa, S. F., Di Iorio, B. R., Campiglia, P., Heidland, A. \u0026amp; Marzocco, S. Inflammation and Oxidative Stress in Chronic Kidney Disease-Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites. \u003cem\u003eInternational journal of molecular sciences\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, doi:10.3390/ijms21010263 (2019).\u003c/li\u003e\n\u003cli\u003eLing, X. C. \u0026amp; Kuo, K.-L. Oxidative stress in chronic kidney disease. \u003cem\u003eRenal Replacement Therapy\u003c/em\u003e \u003cstrong\u003e4\u003c/strong\u003e, 53, doi:10.1186/s41100-018-0195-2 (2018).\u003c/li\u003e\n\u003cli\u003eJohnson, R. J., Sanchez Lozada, L. G., Lanaspa, M. A., Piani, F. \u0026amp; Borghi, C. Uric Acid and Chronic Kidney Disease: Still More to Do. \u003cem\u003eKidney international reports\u003c/em\u003e \u003cstrong\u003e8\u003c/strong\u003e, 229-239, doi:10.1016/j.ekir.2022.11.016 (2023).\u003c/li\u003e\n\u003cli\u003eSarhan, I. I., Abdellatif, Y. A., Saad, R. E. \u0026amp; Teama, N. M. Renoprotective effect of febuxostat on contrast-induced acute kidney injury in chronic kidney disease patients stage 3: randomized controlled trial. \u003cem\u003eBMC Nephrology\u003c/em\u003e\u003cstrong\u003e24\u003c/strong\u003e, 65, doi:10.1186/s12882-023-03114-4 (2023).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable I: Demographics and CKD stage of the study population by their treatment group (\u003cem\u003en\u003c/em\u003e=210)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFebuxostat Group (\u003cem\u003en\u003c/em\u003e=105)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo Group (\u003cem\u003en\u003c/em\u003e=105)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eMean (\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e48.97 (\u0026plusmn;12.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e51.97 (\u0026plusmn;7.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.215*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e19-75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e38-63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e57 (54.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e72 (68.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.220\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e48 (45.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e33 (31.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003eUnit (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e2.70\u0026plusmn;0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e2.54\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.251*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003eUnit (ml/min per 1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e25.28\u0026plusmn;7.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e26.81\u0026plusmn;7.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.392*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eUric acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003eUnit (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e8.55\u0026plusmn;1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e8.10\u0026plusmn;0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.054*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eH/O HTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e90 (85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e99 (94.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.232\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e15 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e6 (5.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eH/O DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e54 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e51 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.821\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 128px;\"\u003e\n \u003cp\u003e54 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e51 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCKD stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eStage 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e36 (34.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e30 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.607\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eStage 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e69 (65.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e75 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 138px;\"\u003e\n \u003cp\u003eBP (mmHg)\u003c/p\u003e\n \u003cp\u003eMean (\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eSystolic BP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e137\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e138\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.660*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 112px;\"\u003e\n \u003cp\u003eDiastolic BP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e86\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e84\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.250*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH/O: Signifies a history of; HTN: Hypertension; DM: Diabetes mellitus; BP: Blood Pressure. \u0026nbsp;Unless specified otherwise, the data are presented as frequencies (in percentages); SD: Standard Deviation. *The P-value was computed through an independent sample t-test. \u003csup\u003e\u0026dagger;\u003c/sup\u003e: P value was obtained through a \u003cem\u003echi\u003c/em\u003e-square test. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable II: Comparison of serum uric acid, serum creatinine, eGFR, systolic BP and diastolic BP between groups during the study period\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters (unit)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime interval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy Groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 17px;\"\u003e\n \u003cp\u003eSerum uric acid (mg/dL)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e8.55\u0026plusmn;1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e8.10\u0026plusmn;0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e6.01\u0026plusmn;0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e8.41\u0026plusmn;0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e4.92\u0026plusmn;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e8.99\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 17px;\"\u003e\n \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e2.70\u0026plusmn;0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.251\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e2.54\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e2.55\u0026plusmn;0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e2.72\u0026plusmn;0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e2.45\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e3.03\u0026plusmn;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 17px;\"\u003e\n \u003cp\u003eeGFR (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e25.28\u0026plusmn;7.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.329\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e26.81\u0026plusmn;7.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e26.08\u0026plusmn;7.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e25.31\u0026plusmn;7.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e27.01\u0026plusmn;8.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 24px;\"\u003e\n \u003cp\u003e23.32\u0026plusmn;7.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 17px;\"\u003e\n \u003cp\u003eSystolic Blood Pressure (SBP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e137\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e138\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e131\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e135\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e130\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e134\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 17px;\"\u003e\n \u003cp\u003eDiastolic Blood Pressure (DBP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e86\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e84\u0026plusmn;8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e78\u0026plusmn;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e76\u0026plusmn;5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15px;\"\u003e\n \u003cp\u003eMonth 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003eFebuxostat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e76\u0026plusmn;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 19px;\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003e80\u0026plusmn;7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eP values were derived from independent sample t test; BP: Blood pressure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable III: Changes in serum creatinine and eGFR from baseline from baseline to month 6 in the study groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables (unit)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (\u0026plusmn;SD) values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAt Baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAt month 6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 153px;\"\u003e\n \u003cp\u003eFebuxostat\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eSerum creatinine\u003c/p\u003e\n \u003cp\u003e(mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2.70\u0026plusmn;0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e2.45\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003cp\u003e(ml/min per 1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e25.28\u0026plusmn;7.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e27.01\u0026plusmn;8.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 153px;\"\u003e\n \u003cp\u003ePlacebo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eSerum creatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2.54\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e3.03\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003cp\u003e(ml/min per 1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e26.81\u0026plusmn;7.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e23.32\u0026plusmn;7.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCI: Confidence interval; \u003csup\u003e\u0026dagger;\u003c/sup\u003eP values are derived through a paired sample t test. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable IV:\u003c/strong\u003e \u003cstrong\u003ePercentage of patients experiencing a 10% reduction in eGFR at baseline\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"648\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eeGFR change category\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFebuxostat group (n=105)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo group (n=105)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDecline \u0026ge;10% of baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e42 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e66 (62.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDecline \u0026lt;10% of baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e9 (8.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e12 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNo change or improvement\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e54 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e27 (25.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*P value was derived from \u003cem\u003eChi\u003c/em\u003e-square test. \u0026nbsp; \u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Asymptomatic hyperuricemia, CKD, eGFR, Febuxostat, Serum uric acid","lastPublishedDoi":"10.21203/rs.3.rs-5905053/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5905053/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTherapeutic approaches for addressing asymptomatic chronic kidney disease (CKD) with renal impairment requires careful consideration, as there is a lack of substantial evidence endorsing specific medications. This study examined the outcomes of administering febuxostat to persons diagnosed with asymptomatic hyperuricemia in CKD (stages 3 and 4).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA single-patient blinded; placebo-controlled study was carried out at Chittagong Medical College Hospital in Chattogram 4203 over a one-year period. Participants were randomly assigned to two groups: one group received a daily dose of 40 mg of febuxostat while the other was given placebo tablets. As necessary, diuretics, antihypertensives, and antidiabetics were administered. Evaluations, which included patient history, physical examinations, outcomes, and pertinent tests, were performed at baseline, the 3rd month, and the 6th month.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were 105 similar-baseline patients in each group. The mean serum uric acid (SUA) level in the febuxostat group lowered from 8.55 to 4.92 mg/dL after six months, while in the placebo control it elevated from 8.10 to 8.99. In febuxostat group, the mean eGFR elevated from 25.28 to 27.01 ml/min/1.73 m\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, while in the placebo control it reduced from 26.81 to 23.32. In the febuxostat group, at the six-month mark, eGFR differed across groups following a substantial decrease in systolic and diastolic blood pressure (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn our clinical setting, febuxostat proved more effective than a placebo in reducing serum uric acid levels and maintaining eGFR in patients with stage 3 and 4 CKD. Hence, febuxostat could be employed to treat hyperuricemia-associated asymptomatic chronic renal disease.\u003c/p\u003e","manuscriptTitle":"Febuxostat efficiently reduces the progression of chronic kidney disease in asymptomatic hyperuricemia: An interventional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-07 09:39:54","doi":"10.21203/rs.3.rs-5905053/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-04-09T22:55:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-05T09:41:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"305040241811136804121031579049419978654","date":"2025-04-05T09:36:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161205900276822997533960449502819830823","date":"2025-04-04T09:33:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-04T09:14:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-27T15:55:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Internal Medicine","date":"2025-03-24T06:54:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3586fa8e-e804-4f75-8cb6-8a49740ae0fa","owner":[],"postedDate":"April 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-04-10T19:08:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-07 09:39:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5905053","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5905053","identity":"rs-5905053","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}