Serum Urate Acid Research Articles

Association between specific ultrasound features of joints and impaired kidney function among gout patients.

To investigate the relationship between the specific ultrasonic manifestations of lower limb joints and impaired kidney function in gouty arthritis. In this cross-sectional study, 408 patients with gouty arthritis were divided into two groups based on the status of renal function: normal group (n = 240) and renal impairment (n = 168) group. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joints to detect ultrasound features of double-contour sign (DC) and tophus. Multiple logistic regression analysis was conducted to assess the association between kidney dysfunction and ultrasound features. A number of potential clinical confounders were adjusted in the model. Univariable conditional logistic regression produces several significant risk factors of impaired kidney function which were the highest and current lever of serum urate acid, course of disease, frequency of attack, hyperlipidemia, hypertension, diabetes, coronary heart disease, presence of multiple tophus, and DC (P < 0.05). After correcting the course of disease and other risk factors, tophus was still an independent risk factor of impaired kidney function and the multivariable adjusted odds ratios (95% CI) was 1.789 (1.005-3.185, P = 0.05), however, the association was not significant in DC (OR = 1.098, 95% CI: 0.668-1.803, P = 0.71). The ultrasound feature of tophus was associated with kidney dysfunction in patients with gout, independent of clinical risk factors, which may be helpful in guiding clinical practice.

Вплив терапії, що знижує рівень сечової кислоти, на функцію нирок (IMPULsKF)

Подано дані про дослідження, розпочате в Україні у 2017 році, із дизайном POEM і тривалістю 36 місяців. Його метою є вивчення впливу двох цільових рівнів терапії, спрямованої на зниження підвищеного рівня сечової кислоти (гіперурикемія), на функцію нирок і прогресування хронічної хвороби нирок (ХХН), який визначали за розрахунковою швидкістю клубочкової фільтрації і рівнем альбумінурії, у 180 пацієнтів із подагрою (n = 90) і ХХН (n = 90). Основні поточні завдання включають: 1) оцінку рівня сечової кислоти в сироватці крові (СКСК), що має найбільший потенціал при збереженні функції нирок; 2) виявлення нових нападів подагри залежно від рівня СКСК у пацієнтів як із подагрою, так і з ХХН; 3) безпеку і побічні ефекти цільового і наднизького рівнів СКСК при оптимальному режимі доказової терапії, спрямованої на зниження рівня сечової кислоти, у осіб із ХХН і пацієнтів без неї, але з подагрою.

Evaluation of urate-lowering therapy in hyperuricemia patients: a systematic review and Bayesian network meta-analysis of randomized controlled trials.

Hyperuricemia is a strong precursor of gout, which deteriorates patients' health and quality of life. Sustained adherence to urate-lowering therapies (ULTs) is crucial for efficacy and therapeutic cost-effectiveness. Recently, several new ULTs have been proposed. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy and safety of the current ULTs, focusing on adherence attrition-related adverse event reporting. The Bayesian network meta-analysis was applied to compare ULTs. Drug efficacy and safety were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred. The results were summarized using the pooled estimates of effect sizes (odds ratios), their precisions (95% credible interval), and the ranking probabilities. Thirty-nine RCTs were identified, accumulating 19,401 patients. Consistent with previous studies, febuxostat (≥ 40 mg/day) was superior to other monoagent ULTs. The new findings were as follows: (i) dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse effects when lesinurad is uptitrated is needed, and (ii) terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat ≥ 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events. Evidence from RCTs regarding second-line agents, such as probenecid and pegloticase, remains insufficient for clinical decision-making.Key Points• Dual-agent ULTs were superior to febuxostat alone, and further surveillance on the adverse-effects when lesinurad is uptitrated is needed.• Terminalia bellerica 500 mg/day, a novel xanthine oxidase inhibitor (XOI) made of natural fruit extracts, and topiroxostat 80 mg/day, an XOI used mostly in Japan, could be new effective options for lowering the occurrence of adherence attrition events.

Serum urate goal attainment and associated factors in Chinese gout patients

ABSTRACT We conducted a cross-sectional study with 350 gout patients to investigate serum urate acid (sUA) goal attainment (sUA < 360 μmol/L) and associated factors in Chinese gout patients in the Affiliated Hospital of Nantong University from August 2015 to September 2017. Descriptive statistics, health assessment questionnaire, global visual analog scale for general health and Gout Knowledge Questionnaire were calculated comparing patients at sUA goal or not at sUA goal. Univariate analysis and logistic regression models were applied to analyze data. The proportion of urate-lowering therapy (ULT) use was 61.2% (211/350). The mean ± standard deviation sUA of the participants was 475.07 ± 121.53 μmol/L. Only 17.4% of gout patients attain the serum urate goal, which also means 289(82.6%) patients cannot keep their sUA below the target of 360 μmol/L. The factors associated with sUA goal attainment including age, education level and ULT use. Among these, age, waist hip ratio, ULT, family history of cardiovascular disease was the predictor of sUA goal attainment. In conclusion, more than 80% of gout patients did not achieve sUA goal. Younger and fatter patients were more difficult to control the serum urate level.

Crystal-proven Gout and Characteristic Gout Severity Factors Are Associated with Cardiovascular Disease.

Our aim was to examine the prevalence of cardiovascular disease (CVD) in patients with crystal-proven gout compared to arthritis controls. Further, we analyzed the association between characteristic gout severity factors and CVD to provide further support for a pathogenetic relationship between gout and CVD. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in all referred patients; controls were negative for crystals. Patients' characteristics and different manifestations of CVD and gout severity factors (disease duration, attack frequency, tophi, affected joints, high serum urate acid level, joint damage) were collected. Gout patients were compared with controls for the prevalence of CVD. In addition, the association between characteristic gout severity factors and presence of CVD was analyzed. Data from 700 gout patients and 276 controls were collected. CVD was present in 47% (95% CI 44%-51%) and 24% (95% CI 19%-29%) of gout patients and controls, respectively. Corrected for confounders, gout was still strongly associated with an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37-4.84). In patients with gout, disease duration ≥ 2 years, oligo- or polyarthritis, serum urate acid > 0.55 mmol/l at presentation, and joint damage were independently (p < 0.05) associated with prevalent CVD. Crystal-proven gout was strongly associated with an increased prevalence of CVD. In patients with gout, characteristic gout severity factors were associated with CVD.

Comparative efficacy and safety of urate-lowering therapy for the treatment of hyperuricemia: a systematic review and network meta-analysis.

The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia. Drug efficacy and safety, as outcomes, were measured by whether the target level of serum urate acid was achieved and whether any adverse events occurred, respectively. We derived pooled effect sizes expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The efficacy and safety of the drugs were ranked by cumulative ranking probabilities. Our findings show that febuxostat, benzbromarone, probenecid, pegloticase, and allopurinol were all highly effective at reducing the risk of hyperuricemia compared to placebo. Febuxostat had the best efficacy and safety compared to the other drugs. Furthermore, febuxostat 120 mg QD was more effective at achieving urate-lowering targets (OR: 0.17, 95% CI: 0.12–0.24) and safer (OR: 0.72, 95% CI: 0.56–0.91) than allopurinol.

A Systematic Review of the Economic and Humanistic Burden of Gout.

Gout is a chronic and inflammatory form of arthritis that is often overlooked despite the associated pain caused by acute flares and associated joint damage caused by the development of debilitating tophi. The increasing burden of gout, due to an aging population and the increased prevalence of known risk factors for hyperuricaemia, means that there is a continued need for new and effective urate-lowering treatments. The evaluation of these treatments will require a comprehensive and comparative evidence base describing the economic and humanistic burden of gout, taken from the perspective of patients, the healthcare system, and wider society. The objective of this study is to review and summarise the current evidence of the disease burden related to chronic gout, assessed in terms of both cost and health-related quality of life (HRQL), and to identify key factors correlated with an increased burden. The overall aim is to support the economic evaluation of new treatments for gout, and to highlight key data gaps that may need further study and exploration. Relevant literature dating from January 2000 to July 2014 was sourced through searches of the MEDLINE database via PubMed and The Cochrane Library. Articles published in English and reporting either the economic burden (cost) or the humanistic burden (HRQL/utility) of gout were identified, and key data were extracted and summarised, with key themes and data gaps identified and discussed. Of the 323 studies identified, 39 met the inclusion criteria, of which 17 and 26 were relevant to the economic and humanistic burden, respectively. The economic burden of gout varied according to numerous factors, most notably serum urate acid levels and number of flares and tophi, resulting in higher healthcare resource use most often attributed to hospitalisation and inpatient stay. The incremental direct cost of gout has been suggested in the range of US$3165 to US$5515 (2004 and 2005 values, respectively) climbing to US$10,222 to US$21,467 (2008 values) per annum where patients are experiencing regular acute flares and have tophi present. The humanistic burden of gout was largely due to physical disability and pain resulting from chronic clinical manifestations. Short Form 6 dimensions (SF-6D) assessed utility weights are estimated at 0.53 for a patient with severe gout (≥3 flares/year and tophi) compared with 0.73 for an asymptomatic gout patient with serum acid levels<6mg/dl. The evidence confirms that gout has a growing overall prevalence and represents a significant burden in terms of both direct healthcare cost and HRQL outcomes. In light of this, effective urate-lowering treatments are likely to be valued if they can be clearly demonstrated to be both clinically effective and cost effective. Published data to support healthcare decision making in non-US countries with regards to treatments for gout are currently limited, which is a key limitation of the current evidence base. More research is also required to extend our understanding of the impact of gout on indirect costs, and a need also exists to develop a more comprehensive set of comparative HRQL utility assessments.

Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system.

To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout. We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl. We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation. Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.

Effects of azelnidipine on uric acid metabolism in patients with essential hypertension

Purpose: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients.Methods: Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2–3 months after the administration.Results: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥0.5 or ≥0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥7.0 mg/dL in males and ≥6.0 mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or overexcretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion.Conclusions: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and overexcretion of uric acid.