Uric Acid-lowering Therapy Research Articles

Hyperuricemia suppresses lumican, exacerbating adverse remodeling after myocardial infarction by promoting fibroblast phenotype transition

BackgroundHyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling.ObjectivesWe aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis.MethodsMicroarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays.ResultsHyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-β/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling.ConclusionHyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.

The Impact of Uric Acid-Lowering Therapy on the Progression of Non-dialysis Chronic Kidney Disease: A Prospective Cohort Study.

Background Hyperuricemia treatment can positively influence the progression of chronic kidney disease (CKD). This study aimed to evaluate the impact of uric acid-lowering therapy on the progression of CKD after three months. Materials and methods A prospective cohort study was conducted on 126 patients with non-dialysis CKD in Can Tho Central General Hospital, Vietnam, from December 2018 to December 2019. Adopting a questionnaire survey method to collect information, including demographic characteristics, body mass index (BMI), personal history, previous medical history, diet, and use of drugs with the potential to affect the uric acid levels in the blood. Participants also underwent necessary tests, such as serum uric acid, serum creatinine, and blood lipids. Data were analyzed using SPSS software version 26.0(IBM Corp., Armonk, NY). Results The prevalence of hyperuricemia in patients with non-dialysis CKD was 77.8%, and the average serum uric acid was 494.21 ± 131.57 µmol/L. Patients with a high-purine diet were about 18.85 times as likely to have hyperuricemia as those with a low-purine diet (p < 0.001, OR = 18.85, 95%CI: 4.233-83.938). BMI, stages of CKD, and hypertension were associated with the hyperuricemia rate (p < 0.05). After three months of treatment, 46.2% of patients achieved the serum uric acid target, and the patient group combined allopurinol with changing diet had a higher rate than the patient group changing diet only (p = 0.02). There was a moderate inverse correlation between the difference in serum uric acid and the difference in estimated glomerular filtration rate (eGFR) after treatment (r = -0.5, p = 0.001). Conclusions The effective management of hyperuricemia by combining nonpharmacological (changing diet) and/or pharmacological (allopurinol) therapies may meaningfully improve the glomerular filtration rate in non-dialysis CKD patients with hyperuricemia.

Ultrasound Features in Gout: An Overview.

The accurate diagnosis of gout frequently constitutes a challenge in clinical practice, as it bears a close resemblance to other rheumatologic conditions. An undelayed diagnosis and an early therapeutic intervention using uric acid lowering therapy (ULT) is of the utmost importance for preventing bone destruction, the main point of managing gout patients. Advanced and less invasive imaging techniques are employed to diagnose the pathology and ultrasonography (US) stands out as a non-invasive, widely accessible and easily reproducible method with high patient acceptability, enabling the evaluation of the full clinical spectrum in gout. The 2023 EULAR recommendations for imaging in diagnosis and management of crystal-induced arthropathies in clinical practice state that US is a fundamental imagistic modality. The guidelines underline its effectiveness in detecting crystal deposition, particularly for identifying tophi and the double contour sign (DCS). Its utility also arises in the early stages, consequent to synovitis detection. US measures of monosodium urate (MSU) deposits are valuable indicators, sensitive to change consequent to even short-term administration of ULT treatment, and can be feasibly used both in current daily practice and clinical trials. This paper aimed to provide an overview of the main US features observed in gout patients with reference to standardized imaging guidelines, as well as the clinical applicability both for diagnosis accuracy and treatment follow-up. Our research focused on summarizing the current knowledge on the topic, highlighting key data that emphasize gout as one of the few rheumatological conditions where US is recognized as a fundamental diagnostic and monitoring tool, as reflected in the most recent classification criteria.

A phenome-wide association and factorial Mendelian randomization study on the repurposing of uric acid-lowering drugs for cardiovascular outcomes

Uric acid has been linked to various disease outcomes. However, it remains unclear whether uric acid-lowering therapy could be repurposed as a treatment for conditions other than gout. We first performed both observational phenome-wide association study (Obs-PheWAS) and polygenic risk score PheWAS (PRS-PheWAS) to identify associations of uric acid levels with a wide range of disease outcomes. Then, trajectory analysis was conducted to explore temporal progression patterns of the observed disease outcomes. Finally, we investigated whether uric acid-lowering drugs could be repurposed using a factorial Mendelian randomization (MR) study design. A total of 41 overlapping phenotypes associated with uric acid levels were identified by both Obs- and PRS- PheWASs, primarily cardiometabolic diseases. The trajectory analysis illustrated how elevated uric acid levels contribute to cardiometabolic diseases, and finally death. Meanwhile, we found that uric acid-lowering drugs exerted a protective role in reducing the risk of coronary atherosclerosis (OR = 0.96, 95%CI: 0.93, 1.00, P = 0.049), congestive heart failure (OR = 0.64, 95%CI: 0.42, 0.99, P = 0.043), occlusion of cerebral arteries (OR = 0.93, 95%CI: 0.87, 1.00, P = 0.044) and peripheral vascular disease (OR = 0.60, 95%CI: 0.38, 0.94, P = 0.025). Furthermore, the combination of uric acid-lowering therapy (e.g. xanthine oxidase inhibitors) with antihypertensive treatment (e.g. calcium channel blockers) exerted additive effects and was associated with a 6%, 8%, 8%, 10% reduction in risk of coronary atherosclerosis, heart failure, occlusion of cerebral arteries and peripheral vascular disease, respectively. Our findings support a role of elevated uric acid levels in advancing cardiovascular dysfunction and identify potential repurposing opportunities for uric acid-lowering drugs in cardiovascular treatment.

Relationship between serum uric acid levels and uric acid lowering therapy with the prognosis of patients with heart failure with preserved ejection fraction: a meta-analysis

Relationship between serum uric acid levels and uric acid lowering therapy with the prognosis of patients with heart failure with preserved ejection fraction: a meta-analysis

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA

BackgroundWe investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients.MethodsThis was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment.ResultsThree hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups.ConclusionThis study did not reveal the benefit of Intensive ULT to improve albuminuria levels.(UMIN000026741 and jRCTs051180146).

Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis

BackgroundIt is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients.MethodsComprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia.ResultsA total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]μmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]μmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943).ConclusionsAccording to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial.

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Association of hyperuricemia with ischemic stroke in adult population

Background: Stroke is the second most prevalent cause of dementia, the third biggest cause of mortality, and the top cause of disability globally. In addition to the conventionally recognized risk factors including smoking, diabetes, hypertension, ischemic heart disease, etc. Recent research on acute ischemic stroke has identified fresh risk variables, such as blood calcium, uric acid, homocysteine, and albumin levels. Hyperuricemia is frequently seen in patients with vascular risk factors and either directly or indirectly through the conventional risk factors.&#x0D; Study: Case control study of 200 patients, 100 patients with stroke and 100 unmatched controls were accessed for vascular risk factor and hyperuricemia and odds ratio was calculated.&#x0D; Results: Out of 100 patients in the case group, 25 (25%) and 75 (75%) had and did not have hyperuricemia. Whereas, out of 100 patients in the control group, 07 (7%) and 9 3 (93%) had and did not have hyperuricemia. The P-value was 0.001. Odds ratio was 4.42.&#x0D; Conclusion: Hyperuricemia is linked positively to occurrence of ischemic stroke as evidenced by the positive odds ratio, further studies need to be done whether uric acid lowering therapy is useful in preventing stroke or reducing mortality.

A Mendelian randomization study of serum uric acid with the risk of venous thromboembolism

BackgroundObservational studies have linked hyperuricemia with venous thromboembolism (VTE). We aimed to investigate whether there are causal relationships between uric acid levels and VTE and its subtypes, including deep venous thrombosis (DVT) of the lower extremities and pulmonary embolism (PE).MethodsWe utilized Mendelian randomization (MR) analysis to estimate the causal association in European individuals. We extracted two sets of polygenic instruments strongly associated (p < 5 × 10−8) with uric acid from the CKDGen consortium and UK biobank, respectively. Genetic associations with the risk of VTE, DVT, and PE were obtained from the FinnGen biobank. We used the inverse-variance weighted method as the preliminary estimate. Additionally, we employed MR-Egger, weighted median, and Mendelian randomization pleiotropy residual sum and outlier method as complementary assessments. Sensitivity analyses were performed to test for pleiotropic bias.ResultsThe genetically instrumented serum uric acid levels had no causal effects on VTE, DVT, and PE. Two sets of polygenic instruments used for exposure, along with three complementary MR methods, also yielded no significant association.ConclusionsOur MR analysis provided no compelling evidence for a causal relationship of serum uric acid with the risk of VTE. This suggests that uric acid-lowering therapies in patients with hyperuricemia may not be effective in reducing the likelihood of developing VTE.

#5341 EFFECTS OF URIC ACID-LOWERING THERAPY ON RENAL OUTCOMES IN CKD PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background and Aims It is well known that hyperuricemia and gout play an important role in the adverse cardiovascular and renal events both in patients with and without renal disease. However, the effect of uric acid-lowering therapy (ULT) on renal outcomes of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, our study summarized reliable results draw from published randomized controlled trials (RCTs) to evaluate the effects of ULT on renal and cardiovascular outcomes in CKD patients with asymptomatic hyperuricemia. Method Pubmed, EMBASE, China National Knowledge Internet (CNKI) and the Cochrane Library were searched systematically for trials up to October 2021. RCTs assessing the effects of uric acid-lowering agents on renal and/or cardiovascular outcomes in CKD patients complicated with asymptomatic hyperuricemia were included. Both the fixed-effect and the random-effect models were used. Results A total of 17 RCTs (one trial1 divided patients into two groups according to CKD stages). including CKD patients with asymptomatic hyperuricemia were included in this meta-analysis. Compared with placebo or no treatment group, ULT group showed a higher estimated glomerular filtration rate (eGFR) with a weighted mean difference (WMD) of 3.679 mL/min/1.73 m2, 95%CI [1.592, 5.766] (p = 0.001) and a lower serum creatinine (Scr) with a WMD of -46.131umol/L, 95% CI [-65.643, -26.619] (p&amp;lt;0.0001). Subgroup analysis demonstrated a significant benefit from ULT in patients with CKD stage 1-3 (p = 0.035), from Asian countries (p = 0.005) and those younger than 60 years (p = 0.002). At the same time, ULT was associated with lower incidence of events of doubling of Scr without dialysis (relative risk (RR) 0.314[0.203, 0.485] (p&amp;lt; 0.0001)). However, no difference was found for all-cause mortality, incidence of AKI, progression to end-stage kidney disease (ESKD), and cardiovascular events. In addition, ULT with allopurinol was associated with lower cardiovascular events (RR 0.678[0.473, 0.971] (p = 0.034)). Conclusion ULT could slow down the progression of renal impairment in CKD patients complicated with asymptomatic hyperuricemia, especially for patients under 60 years old, early CKD stage(1-3) and the Asian descent.

#6950 FEBUXIOSTAT AND ALLOPURINOL VERSUS NON-TREATMENT IN HEMODIALYSIS PATIENTS WITH OUTCOMES

Abstract Background and Aims Uric acid is relatively low in hemodialysis because it is removed during dialysis. The therapeutic intervention for hyperuricemia is controversial. RCT of allopurinol and febuxostat has been performed in hyperuricemic patients to inhibit xanthine oxido reductase (XOR) and reduce uric acid levels further improve outcomes. Nonetheless, we reported preventive effect of XOR inhibitors for dialysis patients on Sci Rep 2017, but the difference in the protective effect for CVD events and mortality between XOR inhibitors is insufficient in dialysis patients. Furthermore, febuxostat is also known to be a potent ATP-binding cassette transporter subfamily G member 2 (ABCG2) inhibitor that promotes the accumulation of uremic toxins by excretion from the gut in dialysis patients and hyperuricemic patients. We investigated the preventative effect of XOR inhibitors on outcomes under three year observation for 6575 hemodialysis patients. Method 6575 dialysis patients were divided into baseline 3 groups (ALLO group, FEB group, non-treatment group). Outcomes were all-cause mortality and CVD events, defined by ICD coding using longitudinal data. Causal associations for outcomes of allopurinol (ALLO) or febuxostat (FEB) were analized using 3 years of longitudinal data versus control at each visit, including concomitant drugs, marginal structural models (MSM) that examined the causal effect of ALLO or FEB versus control with weight for adjust covariate using multiple imputation for missing data. Results Over all all-cause death was 1167 / 6575 (17.74%) cases. In non-treated group 993 / 4827(20.57%), ALLO-treated group 98 / 778 (12.60%), and 136 / 970 (14.20%) in FEB-treated group. CVD events 14723,and number of cvd events for each treatment group non-treated 11229 events, ALLO 1377, FEB 2117 events. MSM indicated that ALLO estimated HR 0.35 for all cause mortality versus non-treated group (p&amp;lt;0.001). MSM also indicated that FEB estimated HR 0.42 for all cause mortality versus un treatment (p&amp;lt;0.001). There was no difference of preventive effect between ALLO and FEB for all cause mortality, but each drugs indicated preventive effect in each base line XOR treatment categories. In CVD events, ALLO indicated preventive effect of HR 0.81 versus control (p&amp;lt;0.001). But FEB did not indicated preventive effect of HR 0.98 (95% CI: 0.91 -1.04). ALLO was estimated preventive effect for CVD events against FEB in HR 0.83 (95% CI 0.75-0.92). Conclusion ALLO and FEB had a prevent effect for all-cause mortality, further FEB was not inferior to ALLO in all-cause mortality in the realm of XOR inhibition. Nevertheless, FEB could not indicate preventive effect for CVD events compared with ALLO and control, which is assumed of ABCG2 inhibitory effect. But was not increase risk for all cause mortality or CVD events compared with ALLO and control. This study provide a new suggestion that it is important for CKD patients to apply extrarenal excretion pathway ABCG2 of uremic toxin and uric acid to prevent CV events because of impaired renal function. In humans 70% of uremic toxin is excreted from urine, and 30% from gut. It is required further investigation and treatment strategies of uric acid lowering therapy should be considered about excretion of uremic substances outside of the kidneys.

Uric acid-lowering therapy with benzbromarone in hypertension with asymptomatic hyperuricemia: a randomized study focusing left ventricular diastolic function

Background Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure with preserved ejection fraction (HFpEF). However, there is limited evidence on the effect of uric acid-lowering therapy on left ventricular (LV) diastolic function in this population. In this randomized study, we prescribed benzbromarone, a uric acid-lowering drug, to those with hypertension and asymptomatic hyperuricemia to investigate its clinical benefits by evaluating LV diastolic function, incidence of HFpEF and hospitalization for heart failure and cardiovascular death. Methods 230 participants were randomly assigned into two groups: uric acid-lowering group (benzbromarone) and control groups (without uric acid-lowering drug). The primary endpoint was LV diastolic function evaluated by echocardiography. The secondary endpoint of composite endpoints is the combination of new-onset HFpEF, hospitalization for heart failure and cardiovascular death. Results After a median of 23.5 months’ follow-up (16–30 months), the primary endpoint reflected by E/e’ in benzbromarone group reached a significant improvement when compared to control group (p <.001). Composite endpoints occurred in 11 patients of the control group while only 3 patients occurred in the benzbromarone group (p = .027). We also presented the favorable trend of freedom from the composite endpoints or new-onset HFpEF using Kaplan–Meier curve by log-rank test in benzbromarone group (p = .037 and p = .054). Conclusions Our study demonstrated the efficiency of benzbromarone in hypertensive patients with concomitant asymptomatic hyperuricemia, including the benefits on ameliorating LV diastolic dysfunction as well as improving composite endpoints.

Sodium-glucose cotransporter-2 inhibitors use and the risk of gout: a systematic review and meta-analysis.

To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM). A systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use. Two prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76). This meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.

Hyperuricemia may be associated with muscle wellness in older adults.

Sarcopenia, associated with morbidity and mortality, is a common geriatric syndrome in older adults. In this study, we investigated the relationship between uric acid, which is a powerful antioxidant and has intracellular proinflammatory activity, and sarcopenia in older adults. This is a cross-sectional retrospective study involving a total of 936 patients. The diagnosis of sarcopenia was evaluated based on the EGWSOP 2 criteria. The patients were divided into two groups according to hyperuricemia (for females > 6mg/dl, for males > 7mg/dl); hyperuricemia and control. The frequency of hyperuricemia was 65.40%. Patients with hyperuricemia were older than the control group and female gender frequency was higher (p = 0.001, p < 0.001, respectively). Sarcopenia was negatively associated with hyperuricemia as a result of the adjustment analysis made according to demographic characteristics, comorbidities, laboratory results, malnutrition, and malnutrition risk. (p = 0.034). Besides, muscle mass and muscle strength were associated with hyperuricemia (p = 0.026 and p = 0.009, respectively). Considering the positive effect of hyperuricemia on sarcopenia, avoiding aggressive uric acid-lowering therapy may be a good option in older adults with asymptomatic hyperuricemia.

Musculoskeletal Ultrasound in Monitoring the Efficacy of Gout: A Prospective Study Based on Tophus and Double Contour Sign

In patients with gout receiving uric acid-lowering therapy, musculoskeletal ultrasound has the potential to observe changes in gout lesions. To analyze the effectiveness of uric acid-lowering therapy in patients with gout over one year using musculoskeletal ultrasound as a monitoring technique. Prospective cohort study. A total of 215 patients meeting the 1977 American College of Rheumatology gout classification criteria and treated with uric acid-lowering therapy were separated into two groups, treat-to-target and treat-to-non-target depending on the target serum urate levels. Lower extremity joints were evaluated by ultrasound before therapy (M0), as well as three (M3), six (M6), and twelve (M12) months after therapy. At various moments during uric acid-lowering therapy, the tophus size and the semiquantitative ultrasound scoring system of double contour sign were measured in the treat-to-target and treat-to-non-target groups. Ninety-five tophi (45 in treat-to-target and 50 in treat-to-non-target) and sixty-seven double contour sign (34 in treat-to-target and 33 in treat-to-non-target) were evaluated longitudinally. In both groups, the long diameter, short diameter, and area of tophus in treat-to-target decreased as the duration of uric acid-lowering treatment increased. Differences in the long diameter of tophus between M12 and M0, M3 and M6 were statistically significant (P < 0.05), while differences between the other time points were not significant (P > 0.05). No statistically significant differences were observed in the short diameter and the area of tophus between M0 and M3 (P > 0.05), while there were statistically significant differences between other periods (P < 0.05). In treat-to-non-target, the long diameter, short diameter, and area of tophus showed a slight increase at different uric acid-lowering therapy time points. The differences in the long diameter, short diameter, and area of tophus at different uric acid-lowering therapy time points were not significant (P > 0.05). The semiquantitative ultrasound scoring system of double contour sign of treat-to-target and treat-to-non-target showed a decreasing trend with increasing uric acid-lowering therapy time, with a more pronounced drop in treat-to-target than treat-to-non-target. In treat-to-target, the difference in the semiquantitative ultrasound scoring system of double contour sign at each uric acidlowering therapy time point was significant (P < 0.05). In treat-tonon- target, the difference in semiquantitative ultrasound scoring system of double contour sign scores between M0 and M3 was not statistically significant (P >0.05), but it was statistically significant for the remaining time points (P < 0.05). After one year of uric acid-lowering therapy in patients with gout, an ultrasound indicated that the size of tophus and the semiquantitative ultrasound scoring system of double contour sign score decreased dramatically in the treat-to-target group. Semiquantitative ultrasound scoring system of double contour sign score was dramatically reduced in the treat-to-non-target group, but the size of the tophus remained the same. Therefore, musculoskeletal ultrasound is an effective tool to monitor the efficacy of uric acid-lowering therapy.

Cardiovascular and kidney outcomes of uric acid-lowering therapy in patients with different kidney functions: study protocol for a systematic review, pairwise and network meta-analysis

IntroductionHyperuricaemia has been implicated in the development of kidney function in populations with chronic kidney disease; however, the benefits of urate-lowering therapy (ULT) remain uncertain in different clinical studies. The...

Evaluating the effects of uric acid level reduction on serum vitamin D level in hemodialysis patients

Introduction: The role of vitamin D in metabolism, bone-mineral regulation, and anti-oxidation effect has drawn researchers’ attention toward its exact role in hemodialysis. Objectives: In this study, the effect of uric acid level reduction on serum 25-hydroxy vitamin D levels in hemodialysis patients was assessed. Patients and Methods: This study is a triple-blind clinical trial conducted on 81 hemodialysis patients suffering from asymptomatic hyperuricemia. Serum uric acid levels were assessed at the start of the study. Then patients were divided randomly into two groups of intervention and control. The intervention group received 100 mg of allopurinol tablets daily for two months. The control group received placebo tablets for the same duration. At the end of the study, 25-hydroxyvitamin D and uric acid levels were assessed. Data were analyzed using SPSS software and chi-square, independent t test, Mann–Whitney U, and Spearman’s rank correlation tests. Results: In our study, two groups of control and intervention were similar in terms of patients’ demographic and hemodialysis characteristics. After the intervention, compared to the control group, the serum uric acid levels were significantly lower in the intervention group, while the level of 25-hydroxyvitamin D showed no significant difference between the two groups. Conclusion: In this study, no significant effect of uric acid lowering therapy with vitamin D elevation in hemodialysis patients was detected. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT2015041721803N1; https:// en.irct.ir/trial/18996, ethical code#IR.SKUMS.1395.231).

ASSOCIATION BETWEEN VITAMIN D AND URIC ACID AMONG NORTH CYPRUS ADULTS: FIRST PRELIMINARY REPORT

Objective: The aim of the study is to evaluate the association between serum uric acid (SUA) and 25-OH Vitamin D (25-OH-VIT D). There is no data about the association between hyperuricemia and 25-OH-VIT D deficiency for North Cyprus. Material and Methods: A cross-sectional study was performed on 356 adults aged between 18-75 years in the North Cyprus. Patients socio-demographic information, clinical and biochemical characteristics, eating habits, and lifestyle choices were recorded. Biochemical parameters were evaluated in all patients. Data were analysed by Chi-square test, Student’s t test, and ANOVA, as appropriate. Also, the Gamma correlation coefficient was calculated for the relationship between 25-OH Vitamin D groups and the other variables. Results: The prevalence of 25-OH-VIT D deficiency was 55.9% among the patients (12.86±4.63 ng/mL), the prevalence of 25-OH-VIT D insufficiency (23.44±2.38 ng/mL) was 27%, and 25-OH-VIT D levels were sufficient in only 17.1% of the patients (36.01±5.83 ng/mL). The ANOVA results indicated statistically significant differences SUA for both male and female patients between the 25-OH-VIT D groups. According to the Gamma correlation coefficient values, 25-OH Vitamin D levels were significantly negatively correlated with SUA. Conclusion: In our study indicated a high prevalence of 25-OHVIT D deficiency and insufficiency in North Cyprus adults and we have found a significant association between SUA levels and 25-OH-VIT D. As a result, both vitamin D supplementation and uric acid-lowering therapies are important in protecting patients against future atherosclerotic diseases.