Urate Lowering Research Articles

Impact of Urate Level on Cardiovascular Risk in Allopurinol Treated Patients. A Nested Case-Control Study.

BackgroundGout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known.ObjectivesTo investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol.MethodsWe identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts.ResultsNo association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79–1.28). No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day).ConclusionWe were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.

A qualitative study to explore health professionals’ experience of treating gout: understanding perceived barriers to effective gout management

INTRODUCTION The management of gout is challenging and mainly occurs in primary care. This study aims to explore the experience of treating gout among primary care clinicians and understand the perceived barriers to effective therapy. METHODS Fourteen health professionals from primary care practices in South Auckland were recruited. Each participated in a semi-structured interview exploring their experience of treating and managing gout patients were analysed thematically. FINDINGS Participants described the large burden of gout in their communities and the importance of the clinician-patient relationship in gout management. Four themes summarise the perceived barriers to effective urate lowering therapy (ULT); unique gout factors, eg its intermittent nature and potential for stigmatisation; systemic barriers to optimal treatment, or barriers that emerge from working within a certain organisation; uncertainty about ownership, or who should carry responsibility for overcoming barriers to optimal treatment; and cultural barriers to optimal treatment. CONCLUSION Clinicians in primary practice perceive gout management to be mainly acute rather than preventive care. Patients may be stigmatised and management difficult particularly when diet is emphasised over ULT. Practice nurses are a group potentially available and willing to assist in educating patients. These findings may be helpful in planning for and improving healthcare in gout. KEYWORDS Gout; general practice; uric acid; primary health care; allopurinol; primary prevention.

Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis.

Children with end-stage renal disease (ESRD) suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD). The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD). This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy. They were divided into two groups: Group I (supplemented group, n = 30) received intravenous Vitamin C supplementation and Group II (control, n = 30) received placebo (intravenous saline) for three months. The results are shown as a mean ± standard deviation. Statistical evaluation was performed by SPSS software (version 11.5) using paired t-test. After supplementation with Vitamin C, the serum Vitamin C and high-density lipoprotein levels increased significantly with a significant reduction in the levels of serum uric acid, cholesterol, low-density lipoproteins, and triglyceride at the end of the study period. No significant changes were observed in the control group. Vitamin C can serve as a useful urate lowering medicine in HD patients to avoid complications of hyperuricemia. Furthermore, it had favorable effects on the lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in these patients.

Effect of Allopurinol on Cardiovascular Outcomes in Hyperuricemic Patients: A Cohort Study

BackgroundHyperuricemia and gout have been associated with increased cardiovascular risk. Allopurinol is an effective urate-lowering drug. Whether lowering of urate by allopurinol improves the cardiovascular risk in hyperuricemic patients remains to be established. ObjectiveOur objective was to investigate the effect of allopurinol on cardiovascular outcomes in hyperuricemic patients in an observational setting. MethodsWe had access to a study population consisting of all patients from Funen County, Denmark with high urate levels (≥6 mg/dL) from 1992 to 2010. We linked 4 registries; all blood samples, all in- and outpatient contacts in hospitals, all reimbursed prescriptions and causes of death. We identified all incident allopurinol users and matched them 1:1 to nonusers of urate-lowering therapy, with similar urate levels, by using propensity scores. Hazard ratios were calculated using competing risk regression model, with respect to Antiplatelet Trialists' Collaboration composite outcome (myocardial infarction, stroke, or cardiovascular death) and all-cause mortality. ResultsAmong 65,971 patients with hyperuricemia, we found 7127 patients on allopurinol treatment. In the propensity score-matched cohort we found a hazard ratio of 0.89 (95% confidence interval, 0.81-0.97) for the main outcome among allopurinol treated compared with nonusers of allopurinol. The corresponding hazard ratio for all-cause mortality was 0.68 (95% confidence interval, 0.62-0.74). ConclusionAllopurinol treatment is associated with a decreased cardiovascular risk among hyperuricemic patients.

Allopurinol and kidney function: An update

Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Chronic Kidney Disease.

To determine whether urate lowering therapy (ULT) could delay renal disease progression in hyperuricemic patients with chronic kidney disease (CKD). We performed a retrospective review of hyperuricemic patients with stage 3 CKD followed from September 2005 to July 2014 in Dongguk University Ilsan Hospital, Goyang, Korea. A total of 158 eligible patients were identified and 65 of them were treated with ULT in addition to the usual CKD management. We divided the patients according to the use of ULT and compared the estimated glomerular filtration rate (eGFR) change from baseline value and the proportion of renal disease progression (decline of eGFR > 30% of the baseline value, initiation of dialysis or eGFR < 15 ml/min/1.73m(2)) at the time of last followup. Risk factors for renal disease progression were identified by logistic regression analysis. After a median followup of 118.5 weeks (minimum 25, maximum 465), the ULT group showed better outcomes compared to the non-ULT group in terms of eGFR change from baseline (-1.19 ± 12.07 vs -7.37 ± 11.17 ml/min/1.73 m(2), p = 0.001) and the proportion of renal disease progression (12.3% vs 27.9%, p = 0.01). Goal-directed ULT showed better clinical outcomes compared to maintaining the initial ULT dose. Actual (area under the SUA-time curve adjusted by total observation time period) serum uric acid was significantly associated with the risk of renal disease progression (p for trend = 0.04) and actual serum uric acid level < 7 mg/dl reduced the risk of renal disease progression by 69.4%. ULT significantly delayed renal disease progression in hyperuricemic patients with CKD. Goal-directed ULT seems to be better than continuing the initial ULT prescription.

A MRI Assessment of the Response of Chronic, Occult, Synovial-Based Inflammation of Gout to Serum Urate Lowering Therapy

We have previously demonstrated the severity of synovitis in patients with inter-critical gout did not correlate with serum urate levels (sUA). The aim of this sub-study was to determine if serum urate lowering therapy can improve this chronic synovitis.

Compliance in intercriticalgout patients and its related factors

To study the compliance and its related factors of gout patients during the intercritical period. A total of 218 gout patients were recruited. Compliance and cognition of gout were evaluated via telephone interview. Case control study was performed between compliance patients and non-compliance ones to explore the factors affecting patients' compliance. The association between compliance scores and cognition scores was evaluated by linear regression and correlation analysis. Of 218 patients, 136 valid questionnaires were collected. The investigation showed that 52.9% (72/136) had more than 20 gout attacks so far. Only 15.4% (21/136) patients had no gout attack during the latest one year. The average compliance score was 3.93 ± 1.78 (total score was 8), and the percentage of non-compliance was 69.9% (95/136). Cognition score was 65.63 ± 18.63 (total score was 100). Among the 136 gout patients, 37 patients (27.2%) were non-cognition, 54 (39.7%) were partial-cognition and 45 (33.1%) were fully-cognition. Only 50.7% (69/136) accepted the concept of long term treatment with urate lowering drugs (ULD), 19.9% (27/136) patients knew the uric acid target and 29.4% (40/136) patients had no confidence to control this disease. Case control study revealed that the percentage of non-cognition in non-compliance group was higher than compliance group, and that of partial-cognition and fully-cognition were lower, although differences had no statistical significance (P > 0.05). Besides, health insurance was better for compliance group (P > 0.05). There was linear correlation between compliance and cognition scores (t = 6.83, P < 0.01) among gout patients. This study indicates that efforts should be made to improve recognition and medical coverage for gout, which could be a very rewarding strategy for patients' compliance and gout control.

Real-world treatment patterns of gout patients treated with colchicine or other common treatments for gout in acute care settings: a retrospective chart review study

Objective:To describe real-world treatment patterns of patients receiving colchicine or other treatments during a gout-related emergency room or acute care facility (ER/ACF) visit.Methods:An online physician-administered questionnaire was used to collect chart data on 500 patients with a gout-related ER/ACF visit after 16 October 2009; 250 patients receiving colchicine (Colchicine Cohort) and 250 receiving NSAIDs, systemic corticosteroids, narcotics, allopurinol, febuxostat, pegloticase, probenecid, or sulfinpyrazone (Other Cohort). Patient characteristics and treatment received/prescribed during the ER/ACF visit (Period 1 [P1]), at discharge (P2), and at the first follow-up visit (P3) are reported.Results:A total of 45 rheumatologists and 63 primary care physicians participated in the study. Patient mean age was 51 years and 74.8% were male. The most common treatments in the Other Cohort were NSAIDs (59.6%), systemic corticosteroids (45.2%), and narcotics (33.6%). The 500 patients contributed 307 distinct treatment patterns from P1 to P3. Of the 20.6% patients not prescribed a treatment in P2, 60.2% were restarted on a treatment in P3. Of the 78.6% treated patients in P2, 27.0% had a treatment adjustment (dose increase, treatment add-on, or initiation of a different gout-related treatment – not with a urate lowering therapy only) in P3; for 72.6% of these patients, physicians justified the treatment adjustment by inadequacy of the treatment for maintenance therapy, insufficient dosage, or inadequate response. In the Colchicine Cohort, 60.8% of patients were prescribed colchicine consistently from P1 to P3, while 26.8% and 17.7% of patients in the Other Cohort were prescribed consistently NSAIDs and systemic corticosteroids from P1 to P3, respectively.Limitations:Specific nature of the acute gout-related symptoms or potential attack/flare during the ER/ACF visit was not recorded.Conclusion:Real-world clinical practice reveals a substantial number of distinct treatment patterns and frequent treatment adjustments by treating physicians for patients with a gout-related ER/ACF visit.

Échographie dans les arthropathies microcristallines

Gout and pseudogout are crystal-related diseases secondary to a metabolic disorder. The consequences are: (i) deposition in joints, synovium and tendons and (ii) possibility of inflammatory arthritis. The gold standard for diagnosis is the visualization by optic microscopy of crystals in synovial fluid. However, diagnosis is sometimes difficult and imaging can help the physician to diagnose this diseases. Radiography is not sensitive in early gout and sometimes normal in pseudogout. Thus, ultrasonography (US) might appear as a useful tool in the management of these diseases. In gout, two US features are specific: the double contour sign and aggregates evocating of tophus. Moreover, these signs can disappear under efficient urate lowering therapy. In pseudogout, the interest of US is mainly for the diagnosis by direct visualization of calcifications in hyaline cartilage and fibrocartilage. In pseudogout, US is more sensitive than radiography to detect these calcifications. In summary, US appears to be useful for diagnosis and management of these two crystal-related diseases.

Update on hyperuricaemia and gout with evidence based management guidelines

Gout is now the leading cause of inflammatory arthritis, affecting 1–2% of the population. The metabolic syndrome, cardiovascular risk factors, cardiovascular events and mortality are more common with gout. However, the role of uric acid as an independent risk factor is inconclusive. The identification of urate transporters has improved our understanding of urate homeostasis and identified targets for the development of newer drugs. Experience with ultrasound and dual energy computed tomography led to the detection of urate crystals in patients with asymptomatic hyperuricaemia. Several evidence-based management guidelines are now available. The dietary and lifestyle recommendations focus on general health and management of comorbidities. A low dose colchicine regimen is effective and better tolerated than the traditional use of higher doses in acute gout. Alternative measures for acute gout include non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. Allopurinol is the most widely used initial therapy; treatment is started with 100 mg or less per day, and titrated upwards to achieve a target level of 0.36 mmol/l (in patients with tophi, a lower target of 0.30 mmol/l is recommended). A new non-purine more potent xanthine oxidase inhibitor, febuxostat, is available (currently not registered in South Africa). Probenecid is the most widely used uricosuric agent. Prophylactic therapy with colchicine, NSAIDs or corticosteroids is used when urate lowering therapy is initiated. Although the cause of gout is known and effective treatment is available, gout is poorly managed worldwide with failure to achieve the target urate level.

Rational pharmacotherapy (RPT) in goutology: Define the serum uric acid target & treat-to-target patient cohort and review on urate lowering therapy (ULT) applying synthetic drugs

A gout revolution is at hand as can be seen from the number of publications and our recent increase in a better understanding of gout regarding imaging, regarding pathogenetic involvement of crystals, cells and cytokines, as well as regarding new pharmacotherapeutic options. We should now focus on rational pharmacotherapy to significantly improve gout care. With modern combinations of xanthine oxidase inhibition PLUS uricosuric all serum urate concentrations can be targeted. The pharmacotherapeutic literature of synthetic urate lowering treatment is reviewed and a plea is given for rational pharmacotherapy combining different modes of action aiming at the rheumatologically predefined optimal serum urate concentrations instead of a more reluctant approach to just lower a serum urate to any lower level with a fixed dose allopurinol.

Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis.

BackgroundHyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and cardiovascular disease. We performed a systematic review and meta-analysis of randomized controlled trials to assess the benefits and risks of treatments that lower urate in patients with stages 3-5 CKD.MethodsWe searched MEDLINE, EMBASE, CENTRAL, Web of Science and trial registers for randomized controlled trials (RCTs) without language restriction. Two authors independently screened articles, assessed risk of bias and extracted data. Data obtained included serum uric acid, serum creatinine or other estimates of glomerular filtration rate, incidence of end-stage renal disease (ESRD), systolic and diastolic blood pressure, proteinuria, cardiovascular disease and adverse events.ResultsFrom the 5497 citations screened, 19 RCTs enrolling 992 participants met our inclusion criteria. Given significant heterogeneity in duration of follow-up and study comparators, only trials greater than 3 months comparing allopurinol and inactive control were meta-analyzed using random effects models. Pooled estimate for eGFR was in favour of allopurinol with a mean difference (MD) of 3.2 ml/min/1.73 m2, 95% CI 0.16-6.2 ml/min/1.73 m2, p = 0.039 and this was consistent with results for serum creatinine. Statistically significant reductions in serum uric acid, systolic and diastolic blood pressure were found, favouring allopurinol. There were insufficient data on adverse events, incidence of ESRD and cardiovascular disease for analysis.ConclusionsAdequately powered RCTs are needed to establish whether treatments that lower urate have beneficial renal and cardiovascular effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0047-z) contains supplementary material, which is available to authorized users.

Pharmacogenetic considerations in the treatment of gout.

Gout is one of the most common forms of arthritis and the prevalence is increasing. Management comprises rapid and effective control of the inflammation in acute gout and sustained urate lowering in the long term. Improving the outcomes for cheaper old drugs and for the increasing number of new, more expensive agents is an important clinical goal. The role of pharmacogenetics in predicting response and adverse events to gout therapies is of considerable interest. Currently, prospective screening is employed to detect HLA-B*5801 carriage and glucose-6-phosphate dehydrogenase deficiency, to minimize occurrence of allopurinol hypersensitivity and pegloticase-related hemolytic anemia. In the future it is likely that other genetic markers of drug response will make the transition to clinical practice to further improve the efficacy and safety of gout therapies. In this review, we will examine the potential clinical relevance of specific genetic variants in the management of gout.

Seasonality of gout in Korea: a multicenter study.

The object of this study was to evaluate the seasonality of gout in Korea. We retrospectively examined data from 330 patients seen at nine rheumatology clinics, treated with urate lowering therapy (ULT) more than one year after stopping prophylactic medication. Demographic data, clinical and laboratory features, and seasonality of gout onset and flares were collected. Season was classified in three-month intervals. The mean age was 52.2 yr and mean disease duration was 26.8 months. The male to female count was 318:12. The onset of acute gouty attacks was obtained in 256 patients. Gout developed most commonly in summer season (36.7%) (P<0.001) and in June (15.6%, P=0.002). During ULT, there were 147 (male 97.3%) gout flares. Although there was no statistically significant difference, gout flares were more common in summer (30.6%). Aggravating factors were identified in 57 flares: alcohol (72.0%) was most common. In the patients who attained target serum uric acid (<6 mg/dL) at the end of prophylaxis, gout flares were high in fall (35.8%) and September (17.0%). In Korea, the summer is most common season of gout onset and there is a tendency for gout flares to increase during ULT in summer/fall season.

Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.

Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP)concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

Management of gout in general practice--a systematic review.

This systematic review aims to summarise published evidence that assessed the management of gout in regard to the following: prescription of urate lowering therapy (ULT), monitoring of serum urate levels (sUA) and allopurinol dosing in patients with renal impairment, lifestyle advice and acute management of gout. Studies investigating the management of gout in general practice (GP) were identified by searching PubMed and Scopus databases. To be eligible for inclusion, studies had to be focused on the GP setting alone. Studies were also excluded if they examined diagnosis without exploring management of gout. Editorials and reviews were excluded. A total of nine studies were identified. Eight studies explored the proportion of gout patients currently on ULT. Six out of the eight studies revealed that ULT was prescribed in less than 50% of gout patients. Four studies considered the monitoring of sUA levels in gout patients. The results were generally similar throughout studies indicating sub-optimal management. Only two studies examined the monitoring of sUA levels specifically in patients who were prescribed ULT. The two studies showed 28 and 38% of patients on ULT had their sUA levels monitored. Two studies examined the dosing of allopurinol in renally impaired patients and revealed that 74-78% of renally impaired patients had an appropriate allopurinol dose of less than 300mg. This systematic review suggests that gout is sub-optimally managed in general practice. However, more studies with a larger sample size focusing on active patients are required to provide more definitive evidence.

Current gout treatment and flare in South Korea: Prophylactic duration associated with fewer gout flares.

To evaluate treatment patterns and clinical factors affecting gout flare in South Korea. We retrospectively examined data from 401 patients seen at nine rheumatology multicenter clinics, under urate lowering therapy (ULT) more than 6months after stopping prophylactic medication. Demographic data, clinical and laboratory features were collected at the initiation of ULT, upon stopping prophylaxis, and 6months after. The mean age was 52.2years and mean disease duration was 25.0months. The male-to-female count was 387:14. The most common ULT starting agent was allopurinol 83.8%. Colchicine (62.3%) was the most commonly prescribed prophylactic agent. During ULT, 134 of the 401 patients (33.4%) experienced at least one gouty attack in the period from stopping prophylaxis to 6months later. The duration of prophylaxis was different between those with serum uric acid levels below 6mg/dL and those over 6mg/dL (P=0.001). Of the 179 patients (44.6%) who attained target serum uric acid (SUA) levels (6mg/dL) at the end of prophylaxis, those taking <6months of prophylaxis suffered more frequent flares than those taking it ≥6months (42.9% vs. 26.3%, P=0.041). The time interval to the first attack after stopping prophylaxis was shorter in the <6months group than the ≥6months group (13.5weeks vs. 22.5weeks, P=0.007). Prophylaxis more than 6months from initiation of ULT, and achieving target SUA (<6mg/dL) at the time of stopping prophylaxis is associated with fewer gout flares during ULT.

THU0581-HPR Effectiveness of A Rheumatology Nurse Follow up Programme in Achieving the Desired Target Serum Urate Levels for Patients with Gouty Arthritis

BackgroundUrate lowering therapy (ULT) can effectively reduce serum urate level (SUA) and flares for gout, thereby minimizing progressive joint damage. Despite advances in therapies for gout and the publication of...

SP0064 Imaging Biomarkers as A Useful Tool in Gout Disease

Conventional radiography can show characteristic features of gouty arthritis such as intraosseous cysts or large erosions with overhanging edges in an advanced tophaceous stage. For early diagnosis, however, conventional X-rays...