Uric Acid-lowering Therapy Research Articles

The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

OBJECTIVES:Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions.METHODS AND RESULTS:A total of 788 patients with relatively normal baseline serum creatinine (<1.5 mg/dL) undergoing percutaneous coronary intervention were prospectively enrolled and divided into a hyperuricemic group (n = 211) and a normouricemic group (n = 577). Hyperuricemia is defined as a serum uric acid level>7 mg/dL in males and >6 mg/dL in females. The incidence of contrast-induced acute kidney injury was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% vs. 1.4%, p<0.001). In-hospital mortality and the need for renal replacement therapy were significantly higher in the hyperuricemic group. According to a multivariate analysis (adjusting for potential confounding factors) the odds ratio for contrast-induced acute kidney injury in the hyperuricemic group was 5.38 (95% confidence interval, 1.99-14.58; p = 0.001) compared with the normouricemic group. The other risk factors for contrast-induced acute kidney injury included age >75 years, emergent percutaneous coronary intervention, diuretic usage and the need for an intra-aortic balloon pump.CONCLUSION:Hyperuricemia was significantly associated with the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine after percutaneous coronary interventions. This observation will help to generate hypotheses for further prospective trials examining the effect of uric acid-lowering therapies for preventing contrast-induced acute kidney injury.

Rilonacept (interleukin‐1 trap) for prevention of gout flares during initiation of uric acid–lowering therapy: Results from a phase III randomized, double‐blind, placebo‐controlled, confirmatory efficacy study

To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acid-lowering therapy (ULT). In total, 241 adult patients with gout, ≥2 gout flares within the past year, and a serum urate level ≥7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16. More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported ≥1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups. Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation.

Adherence to uric acid treatment guidelines in a rheumatology clinic

The aim of this study was to evaluate adherence to recommended serum uric acid levels in the rheumatology outpatients department of a university teaching hospital. We performed a retrospective study of all patients with a definitive diagnosis of gout attending our subspecialty gout clinic between 1 January 2010 and 31 December 2010. We evaluated adherence with two recently suggested uric acid thresholds, <300 μmol/L (<5 mg/dL) and <360 μmol/L (<6 mg/dL). Patient management was judged to adhere to the guidelines if either (1) the latest serum uric acid level was less than the specified guideline targets or (2) uric acid-lowering therapy was titrated upwards or the agent changed if the serum uric acid was above the guideline targets. One hundred two patients with a definitive diagnosis of gout attended the outpatients department between 1 January 2010 and 31 December 2010 and were included in the study. Median serum uric acid level was 331 μmol/L (IQR 276-456 μmol/L). Eighty-six patients (84 %) were treated with allopurinol, six patients (6 %) were treated with febuxostat (one of whom also received probenecid), and one with rasburicase. In 80 patients (78 %), the management adhered to a target guideline of <360 μmol/L (<6 mg/dL). In 66 patients (65 %), the management adhered to a target guideline of <300 μmol/L (<5 mg/dL). A treat-to-target approach has the potential to improve patient outcomes in the management of gouty arthritis. Our study shows encouraging results with the majority of patients on appropriate therapy and reaching recommended targets.

Biologic Gout Drug Fails an FDA Panel Safety Sniff Test

Silver Spring, Md. – Safety concerns about a possible increased cancer risk have scuttled, for now, the approval of the interleukin-1 inhibitor rilonacept. A Food and Drug Administration advisory panel unanimously voting in May against recommending its approval. The FDA's Arthritis Advisory Committee voted 11 to 0 that the safety and efficacy data on rilonacept did not support approval for the prevention of gout flares during the initiation of uric acid-lowering therapy in adults with gout. Rilonacept, marketed as Arcalyst, was approved by the FDA in 2008 for the chronic treatment of familial cold autoinflammatory syndrome and Muckle-Wells syndrome (or cryopyrinassociated periodic syndromes), rare genetic disorders. Preclinical and clinical data indicate that interleukin-1 (IL-1) plays a role in triggering gout flares during the initiation of uric acid–lowering therapy, according to Regeneron Pharmaceuticals, which makes the drug. The dose for which Regeneron was seeking approval was a loading dose of 160 mg followed by a weekly dose of 80 mg for 16 weeks. Over a period of 16 weeks, treatment with the 80-mg dose was associated with a statistically significant reduction in the mean number of gout flares – the primary end point – compared with placebo. Those on the 80-mg dose had a mean of 0.29–0.35 gout flares per patient, compared with a mean of about one gout flare per patient on placebo, with no significant differences between the two rilonacept doses. In the two studies, 19% and almost 26% of those on the 80-mg dose had at least one gout flare, compared with almost half of those on placebo. Several panelists raised the issue of whether it was worth exposing patients to a biologic therapy when they had a 50% chance of not having a flare. In a pooled database of the two pivotal studies and two other gout studies comparing the effectiveness of the 160-mg dose of rilonacept in about 1,000 patients to placebo in almost 400 patients, no significant increase in serious infections was observed in patients treated for 16 weeks. However, six malignancies were diagnosed during treatment with rilonacept, compared with none among those on placebo. FDA reviewers noted that while this number was low and the types of malignancies were not unusual for the typical gout patient, the lack of any malignancies among those on placebo and the biologic plausibility for an increased malignancy risk with a biologic immunosuppressant was a concern and suggested it would be useful to have data on a period longer than 16 weeks. Although most panelists agreed there was evidence that the treatment was effective in reducing gout flares, they said the effect was modest, and that they would be reluctant to use it as a first-line treatment. They said that it would be useful for patients who are intolerant or refractory to NSAIDs and/or colchicine, but added that these types of patients comprised only a small group of patients in the pivotal trial, and that 16 weeks was not long enough to evaluate safety because it was likely that the treatment would be used for longer periods of time. Several panel members questioned why the company did not compare rilonacept to an active control, such as colchicine, which is one of the main drugs used to prevent gout flares during the initiation of uric acid–lowering therapy. The FDA usually follows the recommendations of its advisory panels. The panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver but not at this meeting.

Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery

Serum uric acid (SUA) is a novel risk factor for acute kidney injury (AKI), which adversely affects renal blood flow autoregulation, glomerular filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot study investigated the effect of lowering SUA therapy on AKI, by using traditional and non-traditional markers. In this prospective, double-blind, placebo-controlled, randomized pilot trial, 26 hyperuricemic patients undergoing cardiac surgery were randomized to receive rasburicase or placebo in the preoperative period. Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo. Despite no difference in primary endpoint, the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in subjects with higher SUA levels, more severe renal dysfunction (baseline GFR ≤ 45 mL/min/1.73 m(2)) or heart failure (left ventricular ejection fraction ≤45 %). In this study, rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However, the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury.

Pegloticase: A Novel Agent for Treatment-Refractory Gout

To evaluate efficacy and safety of pegloticase, approved by the Food and Drug Administration in September 2010 for treatment of patients with chronic treatment-refractory gout. Literature searches were conducted using PubMed (1948-January 2012), TOXLINE, International Pharmaceutical Abstracts (1970-January 2012), and Google Scholar using the terms pegloticase, puricase, PEG-uricase, gout, uricase, and Krystexxa. Results were limited to English-language publications. References from selected articles were reviewed to identify additional citations. Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of pegloticase for the treatment of chronic treatment-refractory gout were included. Pegloticase represents a novel intravenous treatment option for patients who have chronic gout refractory to other available treatments. Pegloticase is a recombinant uricase and achieves therapeutic effects by catalyzing oxidation of uric acid to allantoin, resulting in decreased uric acid concentrations. Results of published trials demonstrate the ability of pegloticase to maintain uric acid concentrations below 7 mg/dL in patients with chronic gout. Data supporting reduction of gout flares are limited. Pegloticase is well tolerated but associated with gout flares and infusion reactions. Other adverse events include nausea, dizziness, and back pain. During Phase 3 trials, 2 patients in the pegloticase biweekly group and 1 in the monthly group experienced heart failure exacerbation; another patient in the monthly group experienced a nonfatal myocardial infarction. Providers should exercise caution before administering pegloticase to patients with cardiovascular disease. The cost burden and safety profile may limit its use in practice, in addition to limited data available to support decreases in patient-centered outcomes (eg, gouty attacks). Pegloticase is an effective option for patients with symptomatic gout for whom current uric acid-lowering therapies are ineffective or contraindicated.

Axial (Spinal) Gout

Gout is a common metabolic disorder resulting from supersaturation of uric acid in extracellular fluid and deposition of monosodium urate crystals in tissues. Gouty arthritis typically affects the peripheral joints of the appendicular skeleton, especially the feet and hands. Gouty involvement of the spine, however, is not as rare as generally perceived. Although it may be asymptomatic, tophaceous axial gout is also a well-documented cause of acute back pain, radiculopathy, and frank cord compression. As with the appendicular skeleton, it takes several years of gout before radiological evidence of erosive change or tophi is apparent in the axial skeleton. This is best detected by CT imaging. The sequelae of cord compression can be reversed with timely surgical intervention and maintenance of uric acid-lowering therapy. The long-term effects of urate-lowering therapies on axial gout have not been studied.

Uric Acid and Chronic Kidney Disease: New Understanding of an Old Problem

Although an elevation of serum uric acid level is often associated with chronic kidney disease (CKD), it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of CKD. Recent epidemiologic studies in healthy populations or in subjects with established kidney disease have reported the independent role of uric acid in lowering glomerular filtration rate and increasing the risk for new-onset kidney disease. Furthermore, lowering uric acid in patients with established renal disease has been reported to stabilize renal function independent of other confounders, suggesting a causative role of elevated uric acid in progression of CKD, rather than as an incidental finding related to CKD severity. In this manuscript we will discuss the potential role of uric acid in the development and aggravation of CKD based on epidemiologic, clinical and experimental studies. Given the worldwide epidemic of CKD, the importance of identifying modifiable risk factors of CKD, and the clinical implication of hyperuricemia in CKD, we propose large randomized clinical trials to investigate whether uric acid-lowering therapy can slow the progression of CKD.

For an effective management of gout

Management of gout, the most common inflammatory joint disease among men older than 40 years of age, is often suboptimal. Uric acid—a by-product of purine metabolism—scavenges free radicals and is associated with a reduced risk of several conditions, including multiple sclerosis, Parkinson’s disease and Alzheimer’s disease. However, crystals of sodium urate in joints produce extremely painful attacks of acute gout during which some people cannot wear socks or bear the touch of bed sheets. If drugs and lifestyle changes do not adequately treat the underlying hyperuricaemia, patients can develop recurrences and chronic tophaceous gout. Co-morbidities are common. Therefore, nurses should consider screening patients with gout for hypertension, dyslipidaema, glucose intolerance and microalbuminuria. Effective gout management depends on good communication with patients. Nurses may need to overcome misconceptions, such as gout being solely self-inflicted through over-indulgence. Most patients need NSAIDs, colchicine, or oral or intra-articular corticosteroids to alleviate acute gout. NSAIDs users at increased risk of peptic ulcers, bleeds or perforations should receive gastro-protective agents. Nurses should consider whether certain medications—such as analgesic aspirin doses, diuretics and ciclosporin—might contribute to hyperuricaemia. Nurses should suggest that patients tackle the risk factors for gout, including being overweight, consumption of purine-rich foods and alcohol. Uric acid-lowering therapy reduces the risk of recurrence and complications. However, nurses need to stress the importance of compliance. This article suggests some ways nurses can enhance management of this extremely common, exquisitely painful, yet often misunderstood, condition.

Relationship between Uric Acid and Subtle Cognitive Dysfunction in Chronic Kidney Disease

Background: Elevated serum uric acid has been associated with cognitive dysfunction and vascular cognitive impairment in the elderly. Serum uric acid is also commonly elevated in chronic kidney disease (CKD), but its relationship with cognitive function in these patients has not been addressed. Methods: Subjects with CKD (defined as eGFR <60/ml/min/1.73 m²) were evaluated for cognitive dysfunction using the validated Standardized Mini-Mental State Examination (SMMSE). Individuals with dementia, depression or other psychiatric disorders were excluded, as were subjects on uric acid-lowering therapy or with serious illnesses such as severe anemia or active or ongoing cardiovascular or cerebrovascular disease. Results: 247 subjects were enrolled. SMMSE scores showed stepwise deterioration with increasing quartile of serum uric acid (26.4; 26.1; 25.5; 25.3, score range 20–30, p = 0.019). Post-hoc analysis demonstrated that there was no linear trend and only groups 1 and 4 were different with respect to SMMSE scores (p = 0.025). Stepwise multivariate linear regression revealed that age, educational status, presence of cerebrovascular disease, and serum uric acid were independently related to SMMSE scores. Conclusion: Serum uric acid levels are independently and inversely associated with mild cognitive dysfunction in subjects with CKD.

Serum CRP in patients with gout and effects of benzbromarone

C-reactive protein (CRP) is associated with increased risk for myocardial infarction, atherosclerosis, and peripheral artery diseases, while increased serum uric acid level is suggested to be independently associated with an increased risk of cardiovascular mortality. Accordingly, to investigate whether hyperuricemia is associated with serum CRP, we compared serum CRP levels between healthy subjects and patients with gout. In addition, we also examined whether benzbromarone has effects on serum CRP levels in patients with gout and the expression of CRP messenger RNA of CRP in the hepatoma cell line HuH7. In the first experiment, 40 healthy males and 43 male patients with gout were enrolled, then blood samples were drawn from each after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells. Log serum CRP levels were not significantly different between the patients with gout and healthy subjects, while log serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (p < 0.01). In addition, log serum adiponectin levels were elevated by 2% after treatment (p < 0.01). Furthermore, our in vitro findings demonstrated that benzbromarone down-regulated IL1beta-stimulated CRP gene expression. These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

Is High Serum Uric Acid a Risk Marker or a Target for Treatment? Examination of its Independent Effect in a Large Cohort With Low Cardiovascular Risk

Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations. Prospective cohort study. 484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia). Serum uric acid. All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors. In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population. A single measurement of uric acid was used. Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.

Uric acid: a novel mediator and marker of risk in chronic kidney disease?

To assess the current data suggesting that uric acid-lowering therapy may be useful in the prevention or mitigation of chronic kidney disease (CKD). Eleven observational studies assessing the potential role of serum uric acid in the prevalence and progression of CKD have been published in the past 2 years. Seven suggest an association, whereas four do not. Recent experimental models and clinical trials have mechanistically linked serum uric acid and hypertension, an established risk factor for CKD. Elevated serum uric acid is a marker for decreased renal function, may have a mechanistic role in the incidence and progression of renal functional decline and likely has a causal role in hypertension and vascular disease. Clinical trials are needed to determine whether uric acid-lowering therapy will be effective in preventing CKD.

Effects of Benzbromarone and Allopurinol on Adiponectin In Vivo and In Vitro

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.

Rheumatology

Rheumatology

Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report

Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10–20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden.

Uric acid lowering therapy: prescribing patterns in a large cohort of older adults

Background:Uric acid lowering therapy (UALT) is considered a chronic treatment for gout. Relatively little is known about adherence to UALT.Methods:We assessed adherence with UALT over a 1-year study period among...

Therapeutic advances in gout

The purpose of this review is to highlight the recent developments in the management of gout. Guidelines for the diagnosis and management of gout from EULAR, quality of care indicators, and outcome measures for clinical trials have been published. The standards of gout diagnosis and management are very low. Allopurinol remains the mainstay for serum uric acid lowering therapy. In an important percentage of patients receiving allopurinol, serum uric acid levels are insufficient to promote crystal dissolution. Febuxostat, a new serum uric acid lowering drug, has shown good results. Information on uricase continues to appear. For treatment of gouty inflammation, etoricoxib (a new cyclooxygenase 2 inhibitor) has been shown to be as effective as indomethacin. Finally, the association of gout with the metabolic syndrome and its comorbidities, and the newly described association of gout with myocardial infarction, bring lifestyle and dietary modifications to the front in the management of gout. Proper gout management requires changes to the physician's attitude towards the disease; essentially: (1) an unequivocal diagnosis based in urate crystal identification, (2) a clearly settled aim of the treatment: crystal elimination from the joints and elsewhere, and (3) proper use of the available therapeutic alternatives. Promoting a proper lifestyle appears to be especially important.

Decision-making about gout by physicians of China and influencing factors thereof

To investigate the decision-making about gout by physicians of China and influencing factors thereof. A questionnaire survey, including 13 multiple choice questions, was divided into 2 stages. The first/stage questionnaire survey was conducted among 121 physicians of the departments of internal medicine and rheumatology respectively during the grand ward rounds, and the second-stage questionnaire survey was conducted among 75 physicians attending a national continuous medical education (CME) workshop of rheumatology. The data thus collected were pooled and analyzed by logistic regression models. 62 effective questionnaires were collected in the first/stage survey, and 38 effective questionnaires were collected in the second-stage survey, both with a missing rate < 10%. 78.3% of the respondents considered aspiration of the joint fluid as critical for the definitive diagnosis of gout, but only 2.4% of the respondents did so frequently. When treating acute gout in otherwise healthy patients, 69.2% of the respondents preferred oral colchicine, and while treating the patients with renal dysfunction, 41.7% of the respondents used corticosteroids or corticotrophin as the first choice. For long-term uric acid-lowering therapy, 99 of them (82.5%) described a variety of incorrect indications, 107 of them (89.2%) initiated the treatment too early (< or = 2 weeks after the remission), and 92 of them (76.7%) failed to sustain the treatment for at least 5 years. Only 17 physicians (14.2%) used prophylaxis while initiating the uric acid-lowering treatment and only 7 of them (5.8%) selected a prophylaxis time of 7 approximately 12 months. Multiple logistic regression analysis showed that only CMD on gout was associated with correct diagnosis strategy (OR 7.1, 95% CI 2.1 approximately 23.7). The management of gout by the physicians in China is often not consistent with that generally accepted internationally. High quality CME may improve the decision-making ability of physicians.

Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase.

Although allopurinol has been available for approximately 50 years, hyperuricemia and its sequelae are not only prevalent, but the incidence and costs associated with this disorder continue to increase. However, several new therapies have been developed. Recombinant urate oxidase has been useful in the treatment of tumor lysis hyperuricemia, and pegylated urate oxidase shows promise in patients with hyperuricemia and gout. Febuxostat and Y-700 are new oral xanthine oxidase inhibitors that are in human clinical trials. Tailoring of antilipid therapy in selected hyperuricemic and hyperlipidemic patients with fenofibrate may be of benefit in lowering blood cholesterol and uric acid levels. Similarly, treatment of selected hyperuricemic patients who also are hypertensive with losartan or amlodipine may be beneficial in lowering blood pressure and hyperuricemia. Despite these advances, new treatments for hyperuricemia are needed.