Urate-lowering Medications Research Articles

A potential marker for increased LDL and hypertriglyceridemia risk

Background and objectives. Serum uric acid (SUA), traditionally associated with gout, is increasingly recognized for its potential role in cardiometabolic disorders, including dyslipidemia. Elevated SUA levels may influence lipid metabolism, thus enhancing cardiovascular disease risk. This study aims to explore the association between SUA levels, dyslipidemia, and related risk factors in a cohort of patients, contributing to a better understanding of their interplay and implications for cardiovascular health. Material and methods. We conducted a retrospective case series involving 30 participants selected from the outpatient Department of General Medicine. The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective design and use of de-identified data. Participants were aged 18 or older with available data on SUA, LDL cholesterol, and triglycerides, excluding those with a history of gout, renal impairment, or current use of urate-lowering medications. Data were analyzed using descriptive statistics, chi-square tests, and Mann-Whitney U tests, with significance set at p <0.05. Results. The study population had a mean age of 54.7 ± 6.3 years and a mean BMI of 28.4 ± 2.4 kg/m². The mean SUA level was 6.9 ± 0.8 mg/dL, LDL cholesterol was 138 ± 13 mg/dL, and triglycerides were 162 ± 25 mg/dL. Dyslipidemia was present in 60% of the participants. Significant associations were found between hyperuricemia and dietary habits, family history of gout, CVD, and dyslipidemia, as well as the duration of hyperuricemia. Conclusion. Elevated SUA levels are significantly associated with dyslipidemia and other cardiovascular risk factors. The findings suggest the importance of managing SUA levels and lipid profiles concurrently to reduce cardiovascular risks. Further research is needed to explore the long-term cardiovascular outcomes of persistent hyperuricemia and dyslipidemia.

Easing the way to achieving target serum urate in people with gout: protocol for a non-inferiority randomised strategy trial using an allopurinol dosing model in Aotearoa/New Zealand (the Easy-Allo Study)

IntroductionGout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.9% of Pacific...

What Is Allopurinol Failure and What Should We Do About It?

Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we provide a framework for assessing allopurinol failure, which includes failure of allopurinol to control serum urate concentrations, failure of allopurinol to control clinical symptoms, and failure of allopurinol due to an adverse drug reaction. Understanding the causes of allopurinol failure underpins the approach required to turn failure into success in gout management.

Влияние терапии аллопуринолом на функцию почек у пациентов с подагрой (результаты ретроспективного когортного исследования)

Background: the treatment of hyperuricemia in gout is considered a potential nephroprotective factor. However, data on the effect of allopurinol on renal function in targeted therapy are scarce. Aim: to assess the effect of allopurinol on renal function after achieving the target serum uric acid (UA) level in patients with gout. Patients and Methods: this single-center retrospective cohort study compared changes over time in glomerular filtration rate (GFR) in patients with gout who received allopurinol for at least 12 months with serum UA level <360 μmol/L (n=274, study group) and patients with gout who did not receive urate-lowering medications (n=179, comparison group). Results: the mean follow-up period was 1.9 years, which was similar in both groups. The serum UA level decreased significantly from 521±31.1 to 331±21.3 μmol/L (p<0.001) in the study group, while it increased from 517±55.2 to 558±33.3 μmol/L (p<0.001) in the comparison group. The mean daily dose of allopurinol in the study group was 302.2±24.2 mg. The mean GFR was 80.0±28.5 ml/min/1.73 m2 at baseline and 80.8±21.5 ml/min/1.73 m2 at the end of follow-up in the study group, and 78.2±21.5 ml/min/1.73 m2 at baseline and 76.3±27.5 ml/min/1.73 m2 at the end of follow-up in the comparison group. The study group showed significant differences in ∆GFR (0.8±0.002 ml/min/1.73 m2) and ∆creatinine (-0.9±0.003 μmol/L) compared to the comparison group (∆GFR: -1.7±0.002 ml/min/1.73 m2, p=0.003; ∆creatinine: 1.9±0.001 μmol/L, p=0.001). Conclusion: the results suggest that allopurinol, when administered at a dose sufficient to achieve serum UA levels below the target value (<360 μmol/L), can preserve renal function in patients with gout. KEYWORDS: gout, allopurinol, urate-lowering therapy, uric acid, renal function. FOR CITATION: Eliseev M.S., Zhelyabina O.V. Effect of allopurinol on renal function in patients with gout (retrospective cohort study results). Russian Medical Inquiry. 2024;8(2):60–65 (in Russ.). DOI: 10.32364/2587-6821-2024-8-2-2.

The Effect of Decrease in Serum Urate for the Risk of Gout Flares During Urate-Lowering Therapy Initiation Among Chinese Male Gout Patients: A Prospective Cohort Study.

Higher baseline serum urate or higher initial urate-lowering medication dose increased risk of gout flares during urate-lowering therapy (ULT) initiation. The decrease in serum urate may play a crucial role in this process. Therefore, we aim to explore the relationship between decrease in serum urate and the risk of gout flares during ULT initiation. A 12-week prospective cohort study of Chinese male gout patients was conducted at Shandong Provincial Clinical Research Center for Immune Diseases and Gout in China. Patients were grouped by baseline serum urate (7-7.9 mg/dL, 8-8.9 mg/dL and ≥9 mg/dL). All patients received febuxostat 20 mg daily during weeks 0-4, then escalated to 40mg during weeks 4-12 if serum urate >6mg/dL. The main outcomes were the number of gout flares and the decrease in serum urate. Poisson regression was performed. A total of 282 participants were enrolled, of whom 260 completed (84, 87 and 89 in each group) from March 2021 to December 2021. A 44.2% of all participants experienced at least one gout flare. In the multivariate Poisson regression 1, Δ serum urate 0-12 weeks (IRR 1.184, 95% CI, 1.062-1.320; P=0.002), the number of gout flares before treatment 1 year (1.017, 1.010-1.024; P<0.001) and tophus (1.580, 1.023-2.440; P=0.039) were independently associated with the number of gout flares. While in the multivariate Poisson regression 2, baseline serum urate (1.256, 1.050-1.503; P=0.013) and the number of gout flares before treatment 1 year (1.014, 1.007-1.022; P<0.001) were independently associated with the number of gout flares, Δ serum urate 0-12 weeks (1.055, 0.923-1.207; P=0.433) was no longer a risk factor. ULT-induced gout flares depend on the degree of decrease in serum urate, which is affected by baseline serum urate. Higher baseline serum urate and greater decrease in serum urate lead to higher risk of gout flares.

The Patient Experience of Gout Remission: A Qualitative Study.

Preliminary remission criteria for gout have been developed. However, the patient experience of gout remission has not been described. This qualitative study aimed to understand the patient experience of gout remission and views about the preliminary gout remission criteria. Semistructured interviews were conducted. All participants had gout, had not had a gout flare in the preceding 6 months, and were on urate-lowering medication. Participants were asked to discuss their experience of gout remission and views about the preliminary remission criteria. Interviews were audio recorded and transcribed verbatim. Data were analyzed using a reflexive thematic approach. Twenty participants with gout (17 male participants, median age 63 years) were interviewed. Four key themes of the patient experience of remission were identified: 1) minimal or no gout symptoms (absence of pain due to gout flares, good physical function, smaller or no tophi), 2) freedom from dietary restrictions, 3) gout is "not on the mind", and 4) multifaceted management strategies to maintain remission (regular urate-lowering therapy, exercise, healthy eating). Participants believed that the preliminary remission criteria contained all relevant domains but considered that the pain and patient global assessment domains overlapped with the gout flares domain. Participants regarded 12 months as a more suitable time frame than 6 months to measure remission. Patients experience gout remission as a return to normality with minimal or no gout symptoms, dietary freedom, and absence of mental load. Patients use a range of management strategies to maintain gout remission.

The Prevalence of Asymptomatic Hyperuricemia in Patients with or Without Psoriatic Arthritis is Associated with a Similar Cardiovascular Risk

Abstract Aim: To investigate the association between cardiovascular burden and monosodium urate (MSU) deposits in the joints of patients with asymptomatic hyperuricemia and no evidence of arthritis and subjects with psoriatic arthritis and hyperuricemia. Patients and methods: A single-center, cross-sectional study including 52 individuals: 39 with asymptomatic hyperuricemia and 13 with psoriatic arthritis and hyperuricemia. All patients underwent ultrasound of the joints by which the presence or absence of MSU crystal deposits was assessed. Subjects underwent transthoracic echocardiography by which left ventricular mass index (LVMI) was estimated. Intima-media thickness (IMT) of the common carotid arteries was measured and the presence of atherosclerotic plaques was registered. Results: We found no difference in the distribution of cardiovascular risk factors between the two groups. Further, no difference in their distribution was found between those who were not treated and those who were treated with urate-lowering medications. The frequency of articular MSU deposits was similar between non-allopurinol-treated and allopurinol-treated individuals (p = 0.554). There was no difference in the frequency of articular deposits between benzbromarone recipients and non-recipients (p = 0.396). We observed no connection between articular MSU deposits and LVMI (p = 0.625), IMT (p = 0.117) and atherosclerotic plaques (p = 0.102). Among untreated and treated with urate-lowering drugs there was no difference in LVMI (p = 0.063), IMT (p = 0.975) and plaque distribution (p = 1.000). Conclusion: We can assume that in patients with asymptomatic hyperuricemia and no evidence of arthritis and in subjects with psoriatic arthritis and asymptomatic hyperuricemia, only the prescription of urate-lowering medications for reduction of urate load and cardiovascular risk is not sufficient.

High-Throughput mRNA Sequencing Reveals Potential Therapeutic Targets of Febuxostat in Secondary Injury After Intracerebral Hemorrhage.

Febuxostat is a urate-lowering medication for the treatment of patients with gout. This study was performed to elucidate the effects and underlying mechanisms of febuxostat on neuronal injury induced by intracerebral hemorrhage (ICH) in mice. The results showed that the administration of febuxostat improved neurological severity scores and blood–brain barrier (BBB) permeability. Moreover, febuxostat attenuated neuronal cell death and cytokine levels compared with the ICH group. Next, we conducted a transcriptome analysis of the neuroprotective effects of febuxostat. The overlapping significant differentially expressed genes (DEGs) were identified. Gene ontology (GO) analysis revealed that the overlapping significant DEGs were most enriched in five items. The intersecting DEGs of the aforementioned five pathways were Wisp1, Wnt7b, Frzb, and Pitx2. In addition, GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that DEGs were mainly involved in the wnt signaling pathway. Furthermore, the expression of Wisp1 and Wnt7b in the perihematomal region at 72 h post-ICH was observed. The results showed that both Wisp1 and Wnt7b were increased in the ICH group and were decreased by the administration of febuxostat. Taken together, the study showed that febuxostat protected against secondary brain injury after ICH and the Wnt7b-Wisp1 pathway was closely related to neuroprotective effects.

Investigation of Allopurinol binding mechanism to allele HLA-A*33:03 by using Molecular Dynamics simulation

Allopurinol (ALP), a xanthine oxidase inhibitor, is an FDA-approved urate-lowering medication used to treat Gout, prevent tumor lysis syndrome, and prevent recurrent calcium nephrolithiasis in hyperuricosuria patients. However, it has been known as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (HSS/DRESS), especially in patients carrying the Human Leukocyte Antigens allele HLA-B*58:01, which is more prevalent in Asian population. However, although patients do not carry the HLA-B*58:01 allele, they still exhibit allopurinol-induced SCAR. Surprisingly, a large number of these patients have the HLA-A*33:03 allele. In this research, we investigated the binding of ALP to the HLA-A*33:03 structure using Molecular Dynamics (MD) simulation. Our results showed that the complex of HLA-A*33:03 and ALP was stable after 100000 ps simulation time. ALP had strong interactions with three important residues locating in the active site of HLA-A*33:03, which include the seven amino acid residues Val 76, Asp 77, Leu 81, Ile 95, Gln 96, Asp 116, and Tyr 123. This data suggests that ALP has strong binding affinity for this allele. Thus, in addition to HLA-B*58:01, HLA-A*33:03 may be a potential screening marker before prescribing Allopurinol for Gout treatment.

Design and implementation of a Pacific intervention to increase uptake of urate-lowering therapy for gout: a study protocol

BackgroundGout is a painful chronic disease which disrupts work and family life and can lead to chronic joint damage. Pacific people in Aotearoa/New Zealand experience significant inequities, with over three times the gout prevalence of the non-Pacific non-Māori populations. Pacific people receive less regular urate-lowering drugs to prevent gout flare-ups, and have nine times the hospitalisation from gout compared with non-Pacific non-Māori people. Rates for Indigenous Māori lie between Pacific and non-Pacific non-Māori. A long-established Collective comprising community members from the Pacific People’s Health Advisory Group, clinical staff from the Pacific Practice-Based Research Network, and University of Auckland researchers have identified that improving Pacific urate-lowering therapy use as the research question of prime importance for improved health outcomes of Pacific people in South Auckland. Building on the existing knowledge, this study aims to develop, implement and evaluate a novel innovative intervention to improve the uptake of urate-lowering therapy by Pacific patients with gout.MethodsThree-phase mixed methods co-design study using the Fa’afaletui research framework following the STROBE statement. Phase1 is observational times series of prevalence of patients with gout, proportion with urate blood-level monitoring and use of urate-lowering medication over past 5 years. In Phase 2 the Collective will workshop new interventions to address previous uptake barriers, using culturally-appropriate Talanga communications with results synthesised in line with Kakala principles. The designed intervention will be implemented and process and outcome evaluations conducted. Finally, an implementation framework will be produced to facilitate further roll-out.DiscussionThe study aims to enhance health and reduce inequities for Pacific people, contribute to creation of Pacific health knowledge and translation of research findings into Pacific health gains. Potential longer-term impact is a gout-management pathway for use throughout Aotearoa/New Zealand. Māori have similar issues with high gout prevalence and low urate-lowering therapy use hence the intervention is likely to translate to Māori healthcare. The project will contribute to Pacific research capacity and capability-building as well as general upskilling of community and practice members involved in the co-design processes.Trial registrationThe Australian New Zealand Clinical Trial Registry is in process, request number 38206, 1-09-2021.

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. Among risk and prodromal markers, physical inactivity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical inactivity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical inactivity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Constipation was highest in individuals with the Firmicutes-enriched enterotype, and physical inactivity was most frequent in the Bacteroides-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2021;90:E1-E12.

High Rate of Adherence to Urate-Lowering Treatment in Patients with Gout: Who's to Blame?

IntroductionGout is commonly associated with low adherence rates, thus limiting the effectiveness of treatment. Nevertheless, informed and empowered patients may be more likely to achieve high adherence. We intend to demonstrate that adherence in clinical practice may reach that achieved in clinical trials.MethodsThis was a transversal study within an inception cohort of patients with gout prospectively followed up. Patients were informed at entrance in the cohort of outcomes, targets, and means to implement for successful treatment. Adherence was evaluated through electronic medication possession ratio (MPR) for urate-lowering medication and oral medications for hypertension, diabetes, and hyperlipidemia for comparison. Factors associated with nonadherence, and the relation between nonadherence and serum urate levels while on treatment were analyzed.ResultsData were retrieved from 336 patients, who showed a mean MPR of 87.5%, with 82.1% of patients showing MPR ≥ 0.8. Rates of adherence for hypertension, hyperlipidemia, and diabetes were quite similar (88%, 87%, and 83%, respectively), although MPR > 0.8 was significantly lower for oral medications for diabetes. Adherence was lower, but nevertheless quite fair, during the first year of follow-up, and increasing over time. Active follow-up and comorbidity were associated with good adherence, and adherence and long-term follow-up were associated with higher rates of achieving serum urate within therapeutic target.ConclusionPatients with gout show high rates of adherence if empowered. Active follow-up and comorbidity are associated with high rates of adherence. Adherence is strongly associated with higher rates of achievement of therapeutic serum urate target.

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease.

Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020;88:320-331.

1525-P: Serum Uric Acid Level Is an Independent Risk Factor for Glomerular Filtration Rate Decline in Patients with Untreated Type 2 Diabetes

Decline in kidney function is a major concern for patients with type 2 diabetes. The importance of serum uric acid level as the risk factor for chronic kidney disease (CKD) remains unconfirmed. We therefore evaluated the relationship between baseline serum uric acid level and the risk of incident CKD among men with untreated type 2 diabetes at baseline examination in a 10-11 years prospective cohort study. We included 717 middle-aged Japanese subjects with fasting plasma glucose level ≥126 mg/dL or HbA1c ≥6.5% at baseline who were not taking hypoglycemic medications nor insulin, who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, who did not have proteinuria nor malignant tumors, and who were not taking anti-hypertensive medications nor urate-lowering medications at baseline. CKD was defined as eGFR &amp;lt;60 ml/min/1.73 m2. Cox proportional hazards models were used in the multivariate analysis. During the 5961 person-years follow-up period, 87 subjects developed CKD. Higher serum uric acid level was associated with an increased risk of CKD after adjustment for age, body mass index, systolic blood pressure, diastolic blood pressure, HbA1c, smoking habits (nonsmokers, past smokers, and current smokers), regular leisure-time physical activity (yes/no), daily alcohol consumption (g ethanol/day), and eGFR at baseline. Multiple-adjusted hazard ratios of CKD for quintile 4 (6.2-6.9 mg/dL) and quintile 5 (≥7.0 mg/dL) of serum uric acid levels were 1.30 (95% CI, 0.73-2.30) and 1.80 (95% CI, 1.04-3.11), respectively, compared with quintile 1 to 3 (0.7-6.1 mg/dL). Moreover, when we modeled serum uric acid level as a continuous variable, serum uric acid level per 1.0 mg/dL increase was significantly associated with a 25% increased risk of incident CKD. In conclusion, higher serum uric acid level is independently and significantly associated with an increased risk of CKD in patients with untreated type 2 diabetes. Disclosure Y. Okada: None. K.K. Sato: None. M. Shibata: None. S. Uehara: None. H. Koh: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None.

AB0920 APPLICATION OF THE EULAR 2016 GUIDELINES FOR URATE-LOWERING THERAPY IN CLINICAL PRACTICE (DATA OF A SIX-MONTH PROSPECTIVE STUDY)

Background:The EULAR 2016 guidelines on gout management provide for a consecutive regimen of urate-lowering medications; however, the possibility of reaching the target uric acid level when using the regimen has not been studied in clinical practice.Objectives:To assess the possibility of reaching the target uric acid level when following the EULAR 2016 guidelines on gout management with use of different xanthine oxidase inhibitors available in Russia.Methods:This monocentric prospective study included 83 gout patients (79 (95%) male and 4 (5%) female patients) with the mean age of 51.3±10.9 years old. The inclusion criterion was indications for urate-lowering therapy in accordance with the EULAR 2016 guidelines. The exclusion criteria were the following: absolute contraindications to all of the study drugs, GFR &lt;30ml/min/1.73m2, and NYHA class III-IV heart failure.At urate-lowering therapy initiation, the patients were prescribed allopurinol with the starting dose of 100mg/day; the dose was titrated until the target uric acid level was reached (maximum up to 900mg/day), and in the patients with GFR between 30 and 60ml/min/1.73m2 – up to 300mg/day. In case of insufficient efficacy of allopurinol (unachieved target uric acid level of &lt;360µmol/L, for the patients with severe gout of &lt;300µmol/L) or development of adverse reactions, allopurinol was replaced with febuxostat with the starting dose of 80mg/day and dose titration up to 120mg/day if necessary. The laboratory tests included serum creatinine level, uric acid level, AST, ALT, creatine phosphokinase, glucose; clinical blood test. The following parameters were assessed: possibility of reaching the target uric acid level when following the suggested regimen, and frequency of development of adverse reactions when using allopurinol and febuxostat.Results:37 (45%) patients had the target uric acid level of &lt;360µmol/L and 46 (55%) pts – of &lt;300µmol/L. The recommended therapy regimen allowed 77 (93%) patients under study to reach their target uric acid level.The target uric acid level was achieved by 44 (53%) out of 79 patients on allopurinol, of whom 36 (82%) received 100-600mg/day, and 8 (18%) – 700-900mg/day. Of the patients with GFR of &gt;60ml/min/1.73m2, 32 (73%) patients achieved their target uric acid level and of those with GFR &lt;60ml/min/1.73m2 – so did 12 (27%).Then the patients on allopurinol with unachieved target uric acid level were prescribed febuxostat (in 30 (77%) cases because of inefficacy of the allopurinol therapy, in 9 (33%) patients because of their development of adverse reactions where 5 pts had a more than doubled level of transaminase (ALT, AST), 2 pts had skin itch and 2 pts had hives).In total, 39 patients received febuxostat, of whom 4 pts were with initial intolerance for allopurinol in past history, and 35 pts after therapy with maximum dose of allopurinol. A febuxostat dose of 80mg/day was associated with achievement of the target uric acid level in 14 (42%) patients and that of 120mg/day – in 19 (58%) patients, therefore, total 33 (85%) patients reached their target uric acid level. Four patients on febuxostat developed adverse reactions: 3 patients had a more than doubled serum transaminase level (ALT, AST) and 1 patient had hives. Also, an insignificant increase in the mean GFR was registered from 73±21.4ml/min/1.73m2 to 78.4±22.5ml/min/1.73m2 which did not differ between the two drugs.Conclusion:The recommended regimen of xanthine oxidase inhibitors in their maximal doses secures reaching the target uric acid level in 93% patients. In 47% patients, allopurinol in maximal doses (up to 900mg/day) does not significantly increase the possibility of reaching the target uric acid level, even though it demonstrates high tolerance.Disclosure of Interests:Maria Chikina: None declared, Maxim Elisеev Speakers bureau: Novartis, Menarini Group, Alium, Olga Sheliabina: None declared

Not Every Picture Tells a Story: A Content Analysis of Visual Images in Patient Educational Resources About Gout

The aim of this study was to evaluate which concepts about gout and its treatment are reflected in images in online educational resources about gout. A Google search was performed to identify English-language patient resources from medical and health organizations and health education websites in 7 countries: Australia, Canada, Ireland, New Zealand, South Africa, UK, and USA. Two raters independently coded the images in the resources into 5 main categories: clinical presentations of gout, urate/monosodium urate (MSU) crystals, medicines, food/healthy lifestyle, and other advice for people with gout. In total, 103 resources were identified; 28 resources without images were excluded. Seventy-one educational resources with a total of 310 images were included in the study sample. Of the 310 images, clinical presentations of gout were depicted in 92 images (30%), food/healthy lifestyle in 73 images (24%), urate/MSU crystals in 50 (16%), medicines in 14 (5%). Urate-lowering medication was shown only in 1 image (0.3%) and just 6 images (2%) depicted a serum urate target. Ninety-one images (29%) did not convey specific information about gout. Key concepts about gout and treatment are underrepresented in the images used in educational resources for patients. A large proportion of the images do not convey useful information about gout or its management.

Internalized and Anticipated Stigmatization in Patients With Gout.

ObjectiveTo investigate the relationship between stigma perception and demographic, clinical, and psychosocial variables.MethodsA sample of 50 patients with gout and prescribed urate‐lowering medication (84% were males, mean serum urate 0.34 mmol/l) completed questionnaires on internalized and anticipated stigma, demographics, clinical gout‐related variables, and psychosocial variables (illness perceptions, illness‐related disability, illness‐related body satisfaction, intentional nonadherence). Serum urate level was obtained from the most recent blood test.ResultsIn this sample, 26% experienced internalized stigma, 26% expected to be stigmatized by friends or family members, and 14% by health care workers. Univariate regression analyses showed that younger age, ethnicity other than New Zealand European, increased severity of gout pain, cognitive and emotional illness perceptions, greater illness‐related disability, and increased intentional nonadherence to urate‐lowering medication were associated with increased internalized and anticipated stigma. Younger age, emotional illness response, and intentional nonadherence were the only variables explaining incremental variance of the experience of anticipated stigma in a multivariate regression model.ConclusionInternalized and anticipated illness‐related stigma was reported by a subgroup of patients with gout. The experience of stigma is associated with younger age, a negative emotional illness response, and intentions to not adhere with a medical treatment.

Making the right thing the easy thing to do: strategies to improve outcomes in gout.

The burden of gout is increasing worldwide. Although urate-lower ing drugs have been available for more than half a century, the initiation and persistence of urate-lowering therapy remain low. Health-care system, practitioner, and patient barriers contribute to the clinical inertia in gout management. Pervasive beliefs about gout as a disease of an indulgent lifestyle that should be managed primarily with dietary modification are key barriers that prevent patients from receiving effective therapy. In light of safety concerns about newer urate-lowering medications, allopurinol, an inexpensive generic medication, is likely to remain the first-line urate-lowering therapy for the foreseeable future. Ensuring that allopurinol is optimally and persistently prescribed is a priority for improved gout management. A health literacy approach that focuses on patient understanding of gout as a chronic disease that requires behaviour change to take long term urate-lowering therapy is important. This approach provides a clear rationale for long-term urate-lowering therapy that is able to dissolve the monosodium urate crystals and ultimately prevent the symptoms of gout. Patient-centred models that use the skills of nurses and pharmacists to facilitate patient understanding can lead to major improvements in gout care. Additionally, systematic quality improvement approaches within practices, while reducing inconvenience and cost to patients, should be a priority.

Effect of Dietary and Supplemental Omega-3 Polyunsaturated Fatty Acids on Risk of Recurrent Gout Flares.

To determine the relationship between omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption (dietary or supplemental) and risk of gout flares. We used data from the Boston University Online Gout Study, an internet-based case-crossover study conducted from February 2003 to January 2012. At the times of gout flares (hazard period) and during gout flare-free periods (control periods), participants completed questionnaires regarding exposures, including supplements and diet, during the preceding 48 hours. We examined the relationship of self-reported n-3 PUFA-rich supplements and fish intake with the risk of recurrent gout flares using conditional logistic regression, adjusting for total purine intake, diuretic use, and other urate-lowering or flare prophylactic medications (allopurinol, nonsteroidal antiinflammatory drugs, or colchicine). Of the 724 participants, 85% met the 1977 American College of Rheumatology preliminary criteria for the classification of the acute arthritis of primary gout. Twenty-two percent of the participants reported some form of n-3 PUFA consumption (supplements, 4.6%; dietary fatty fish, 19%) in the 48 hours preceding a gout flare or flare-free period. The adjusted odds ratios were 1.01 (95% confidence interval [95% CI] 0.63-1.60; P = 0.98) for all 3 supplements combined and 0.74 (95% CI 0.54-0.99; P = 0.04) for consumption of ≥2 n-3 PUFA-rich fish servings. Dietary n-3 PUFA-rich fish consumption, when adjusted for total purine intake, was associated with lower risk of recurrent gout flares, whereas n-3 PUFA supplementation alone, as taken in a self-directed manner, was not. Consumption of specific sources and adequate doses of n-3 PUFA for gout flare prevention warrants further study in an adequately powered clinical trial.

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

Background: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. Methods: A prospective cohort study of 9,116 middle-aged nondiabetic ­Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1–23.0 g ethanol/day), moderate drinkers (23.1–46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. Results: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11–1.70), 1.58 (95% CI 1.28–1.95), 2.27 (95% CI 1.86–2.77), and 3.12 (95% CI 2.56–3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46–0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. Conclusions: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.