Target Uric Acid Research Articles

Features of the course of rheumatoid arthritis and osteoarthritis in patients with asymptomatic hyperuricemia

Introduction. According to numerous studies, the prevalence of asymptomatic hyperuricemia has increased in most countries. Uric acid is an important biomarker of the cardiovascular system, and there are now quite a big number of sources indicating its role in the development of a some chronic metabolic conditions, cardiovascular disease and associated mortality. At present, there is no consensus on the need for urate-lowering therapy in patients with asymptomatic hyperuricemia. There is a limited number of studies examining the problem of asymptomatic hyperuricemia in patients with rheumatic diseases, the features of comorbidity in these conditions, the frequency and effectiveness of urate-lowering therapy.
 Purpose. To study the peculiarities of the course of rheumatoid arthritis and osteoarthritis with associated asymptomatic hyperuricemia and compare them with the ones associated with arthragra.
 Materials and methods. The analysis was performed on the basis of the data collected from the city register of the patients with arthragra and asymptomatic hyperuricemia in St. Petersburg. The data collected included the medical records of 1725 patients with arthragra, 433 patients with rheumatoid arthritis and hyperuricemia and 355 patients with osteoarthritis and hyperuricemia.
 Results. The patients with rheumatoid arthritis and hyperuricemia were more likely to have increased erythrocyte sedimentation rate and C-reactive protein, the highest medium level of erythrocyte sedimentation rate; acute myocardial infarction, chronic heart failure, gallstone disease and non-alcoholic fatty liver disease were more frequently detected. The patients with osteoarthritis and hyperuricemia were more likely to have high total cholesterol, at its highest medium level; stable angina, arrhythmia, varicosity, obesity, prediabetes and type 2 diabetes mellitus were more likely to be detected. Kidney damage was detected more frequently in the patients with arthragra. In the group of rheumatoid arthritis and hyperuricemia urate-lowering therapy was started in 30.95% of the patients, in the group of osteoarthritis and hyperuricemia in 36.06%.
 Conclusions. In rheumatic diseases, hyperuricemia is a common associated condition. Their combination leads to increased risk and frequency of cardiovascular, metabolic and gastroenterological comorbidity. The prescription of urate-lowering therapy to the patients with rheumatic diseases and asymptomatic hyperuricemia with high cardiovascular risk led to the target uric acid levels in 34.58% of the patients with rheumatoid arthritis and 52.08% of the patients with osteoarthritis.

Chronic kidney disease and hyperuricemia: mechanisms of development and clinical manifestations

Hyperuricemiaand gout are diseases that threaten the lives of patients with their cardiovascular complications and the development of chronic kidney disease (CKD). Continuous monitoring of uric acid (MC) levels below 360 μmol/l reduces the number of gout attacks and prevents the development of delayed complications. Timely prescribed and correctly selected hypouricemic therapy contributes to the normalization of metabolic processes, in the glomerular filtration rate (GFR) and the level of albumin excretion, and eliminates the risk factors for the progression of CKD. Febuxostat (Adenuric) ensures the rapid achievement of the target MC numbers and subsequent tight control. It is three times more effective than allopurinol in controlling target uric acid levels, provides a reverse regression of deposited uric acid, and does not require dose adjustment for elderly patients with impaired renal function. This drug is significantly more effective than allopurinol at initially high levels of uric acid, in addition, it has significantly fewer side effects due to the selective blockade of xanthine oxidase.

Adherence to urate-lowering therapy while following the national guidelines for the management of patients with gout (preliminary evidence)

Low compliance in patients with gout is one of the reasons for inadequate disease control.Objective: to study treatment adherence in compliance with the national guidelines for the management of gout patients, which provide for the continuous use of urate-lowering drugs, a gradual increase in their dose until the target serum uric acid (UA) level is reached, prophylactic antiinflammatory therapy, and regular patient monitoring.Patients and methods. This was a prospective single-center study. By now, 60 of the 80 enrolled gout patients had completed the study. The follow-up period was at least 24 weeks, during which allopurinol or febuxostat was used at the final dose. During initiation of urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by dose titration to reach the target UA level (<360 μmol/L) for all patients or <300 μmol/L for those with severe tophaceous gout. Patients with ineffective allopurinol and/or in the presence of its associated adverse reactions were prescribed febuxostat (Azurix®) 80 mg/day; the dose was increased up to 120 mg/day as needed. To prevent acute arthritis attacks, all the patients received a nonsteroidal anti-inflammatory drug (NSAID) at minimal therapeutic doses or colchicine 0.5 mg/day, and in the presence of contraindications to their use, they took glucocorticoid (GC) 7.5 mg/day calculated with reference to prednisolone. The four-item Morisky–Green questionnaire was used to assess patient adherence to therapy.Results and discussion. At 24 weeks after the start of their follow-up, 53 (88%) of the 60 patients received urate-lowering therapy; 38 (72%) of these 53 patients achieved the target UA level. The dose of allopurinol was titrated in 19 patients; and 10 (53%) of them achieved the target serum UA levels. Due to its inefficacy, allopurinol was replaced by febuxostat in 24 patients. In this group, the target UA level was recorded in 16 (67%) patients. Seventeen patients were immediately prescribed febuxostat that could achieve the target UA level in 12 (71%) of them. All the patients enrolled in the study received prophylactic anti-inflammatory therapy: NSAIDs were used in 9 (15%) patients, colchicine and GC were given to 46 (77%) and 5 (8%), respectively. Twenty-six (49%) patients who had completed the investigation were ascertained to have a high adherence therapy. Moderate and low adherence was observed in 9 (17%) and 18 (34%) patients, respectively. High therapy adherence was noted in more than half of cases in the febuxostat group and in 40% in the allopurinol one.Conclusion. High compliance in gout patients can be achieved through the observance of the national guidelines for the treatment of this disease.

The place of febuxostat in the treatment of gout

The curation of patients with gout involves the mandatory prescription of pathogenetic therapy with urate-lowering drugs, among which xanthine oxidase inhibitors, such as allopurinol and febuxostat, are most widely used. According to various national and international guidelines, allopurinol is the first line drug for gout. However, there is a large cohort of patients, in whom the use of febuxostat is not only justified, but is also preferable. First of all, these are patients who are intolerant to allopurinol and at a high risk of severe skin reactions. There is a high risk of mortality and a low probability of achieving the target uric acid level when allopurinol is prescribed for patients with diminished renal function. Taking into account the fact that febuxostat has a pronounced nephroprotective effect, prescribing the drug in these patients will be a more effective way to achieve normouricemia. At the same time, the presence of cardiovascular diseases, although this requires additional caution when choosing therapy, should not be a reason for refusal to take febuxostat, since the results of many studies not only have failed to confirm a higher risk for cardiovascular events during therapy with this drug, but also have shown that it has cardioprotective properties.

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 <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 <360µmol/L, for the patients with severe gout of <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 <360µmol/L and 46 (55%) pts – of <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 >60ml/min/1.73m2, 32 (73%) patients achieved their target uric acid level and of those with GFR <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

AB0932 FACTORS IN ACHIEVING TARGET SERUM URIC ACID LEVELS IN OUTPATIENT GOUT MANAGEMENT IN A MALAYSIAN TERTIARY RHEUMATOLOGY CENTRE

Background:Gout is one of the most common inflammatory arthropathies. A target serum uric acid of less than 300µmol/l is recommended when tophi are present, and less than 360µmol/l for non-tophaceous gout. Urate-lowering therapy (ULT) should be titrated until the target is achieved and long-term maintenance of the target concentration is recommended. Although ULT has been proven to reduce the uric acid level, less than half of treated patients achieved the target serum uric acid (sUA) in real-world clinical practice.Objectives:To assess the mean treat-to-target achievement in outpatient management of gout by the tertiary rheumatology centre and to identify factors influencing the success rate.Methods:Retrospective cross-sectional study of all patients with gout attending out-patient clinics in a rheumatology referral centre from 1stJanuary 2018 until 31stDecember 2018. Electronic medical records were reviewed. The successful target achievement is defined as mean of all available sUA in 2018 which is ≤360 and ≤300µmol/l for non-tophaceous and tophaceous gout respectively. Chronic kidney disease (CKD) is defined as glomerular filtration rate of less than 60ml/min.Results:There were 251 patients analysed with mean age of 56.3±13.8 years and disease duration of 10.5±9.2 years. Majority were males (215, 85.7%) and 133 (53%) patients had tophaceous gout. The rate of success achieving the target SUA level of ≤360 and ≤300µmol/l were 33.9% (40) and 15.8% (21) in non-tophaceous and tophaceous gout respectively. However, in patients who are compliant, the target sUA achieved is 52.4% (33) and 31.7% (19) in non-tophaceous and tophaceous gout respectively. Characteristics of patients who achieved the targeted sUA were patients of more than 50 years old (48, 78.7%), without family history of gout (29, 65.9%), were prescribed colchicine prophylaxis upon initiating ULT (46, 76.7%), with absence of joint erosions (34, 73.9%) and those with normal creatinine clearance (40, 65.5%). There were 120 (48.4%) patients who were compliant to ULT. In 42 compliant patients who achieved target sUA, the mean allopurinol dose is 289.66mg±101.2 and 369.23mg±175 in non-tophaceous and tophaceous gout respectively. Sub-analysis in 31 compliant CKD patients, revealed no difference in allopurinol dose between those who achieved versus non-achieved target sUA (mean 243mg versus 263mg respectively). However, we noted that 11 (61%) CKD patients with tophi did not achieved target sUA at dose less than 300mg allopurinol. Lower achievement of target sUA was significantly associated with presence of tophi (p=0.001), poor compliance (p= 0.000) and presence of more than one comorbidity (p=0.041).Conclusion:There are several challenges in achieving target uric acid level contributed by both patient and clinician factors such as compliance, presence of comorbidity and ULT dose. Our study suggests that higher dosage of allopurinol is required in patients with tophaceous gout, with or without renal impairment. However, the limitation of this study is, the small number of subjects which therefore needsfurtherinvestigation.

Practical application of national clinical guidelines for the management of gout (preliminary data)

The 2018 national guidelines for the management of gout provide a consistent scheme for urate-lowering drugs; however, the possibility of achieving uric acid (UA) targets in its use has not been studied.Objective: to evaluate the effectiveness and safety of the urate-lowering therapy algorithm presented in the national guidelines for the management of gout.Patients and methods. This investigation was a prospective single-center study. It has been currently included 54 patients (91% males) with gout. The follow-up period is not less than 12 weeks of continuous use of allopurinol or febuxostat (Azurix) at the final dose.After the initiation of urate-lowering therapy, allopurinol 100 mg/day was prescribed, followed by dose titration to achieve the UA target that was defined as <360 or <300 μmol/L in patients with severe tophaceous gout. The maximum dose was 900 mg/day; it was 300 mg/day when the glomerular filtration rate was <60 ml/min/1.73 m2 . Patients with the inefficacy of allopurinol and/or the presence of its associated adverse reactions (ARs) were prescribed febuxostat 80 mg/day; the dose was increased to 120 mg/day as needed.For the prevention of acute arthritis attacks, all the patients received a nonsteroidal anti-inflammatory drug (NSAID) at the minimum therapeutic doses or colchicine 0.5 mg/day, and if these drugs were contraindicated, a glucocorticoid (GC) 7.5 mg/day, as calculated with reference to prednisone, was taken.The probability of achieving the serum UA target (<360 or 300 μmol/L) was assessed in patients with chronic tophaceous gout.Results and discussion. 12 weeks after therapy initiation, the UA target could be achieved in 39/50 (79%) patients. The target levels <360 and 360 μmol/L were recorded in 15/21 (71%) and 24/33 (73%), respectively. The UA level <360 μmol/L was noted to decrease in a total of 92% of cases. Febuxostat was given to 41 patients: to 27 (66%) due to the inefficacy of allopurinol and to 14 (34%) due to its ARs. As a result, the UA target was achieved in 30 (73%) patients, and there was a decrease in the UA level <360 μmol/L in 35 (85%).ARs were seen only in 3 febuxostat-treated patients, including 2 patients with previous allopurinol-induced ARs.For the prevention of arthritis attacks, 10 (19%) patients took NSAIDs, 41 (75%) received colchicine, and 3 (6%) used GC. There were no refusals to receive urate-lowering and preventive anti-inflammatory therapies.Conclusion. The proposed treatment regimen allows for achieving the serum UA target in 79% of patients and its decrease <360 μmol/L in 92%. Treatment with febuxostat (Azurix) is associated with its good tolerance, including in the patients who could not use allopurinol because of AR. Preventive anti-inflammatory therapy is likely to improve adherence to urate-lowering therapy.

Understanding and perceptions of gout: an interdisciplinary assessment among patients, physicians and pharmacists in Italy.

The objective was to assess knowledge and therapeutic approaches to the management of gout among healthcare professionals and people with/without gout, in Italy. This was a cross-sectional internet-based survey targeting general practitioners (GPs), specialists, pharmacists, and people with/without gout. Between December 2017 and March 2018, participants completed questionnaires on epidemiology, cause/risk factors, therapy objectives and management/treatment strategies to improve outcomes. Overall, 3184 people completed the survey: 699 GPs, 426 specialists, 655 pharmacists and 1404 subjects from the general population: 126 (9.0%) with and 1278 (91.0%) without gout. Notably, less than half of GPs, specialists and people without gout confirmed the published 1% prevalence of gout in Italy. Lifestyle was acknowledged as the main risk factor for gout by nearly 50% of specialists and GPs, while only 13.8% and 12.4%, respectively, considered the role of genetic factors. Uric acid overproduction was deemed as the cause of gout by 60% of GPs and specialists, whereas insufficient excretion by only 30%. Fewer than half of patients were aware that gout permanently damages joints, and even fewer of the renal and cardiovascular implications (19.4% and 12%, respectively); moreover, most people without gout replied that their doctor had never talked with them about uric acid and its correlation with gout development. Finally, GPs were divided on uric acid target levels (48.3% said <6 mg/dL and 18.9% <7 mg/dL). Despite major advances in the knowledge of physiopathological mechanisms of gout, the results of our survey highlight the many treatment and knowledge gaps in its management. Cooperation between multidisciplinary teams is required to break down barriers and ensure optimal treatment with effective and innovative agents of this ever-increasing debilitating condition.

Gout and Its Management in Clinical Practice

Gout and Its Management in Clinical Practice Abstract. Resolution of an acute attack is usually the prime objective in routine clinical management of gout. Crystal identification in synovial fluid by polarised light microscopy is considered the diagnostic gold standard. Imaging procedures such as high-resolution ultrasonography are also useful. Non-steroidal anti-inflammatory drugs, steroids and colchicine (not approved in Switzerland, available from pharmacies) are used to treat an acute gout attack. Just as important as the diagnosis and treatment of an acute attack is the long-term management of hyperuricaemia in order to prevent further gout attacks as well as possible renal, cardiac or metabolic complications. Therefore, patients with a confirmed diagnosis of gout should, apart from non-pharmacologic interventions, receive hypouricaemic therapy with a target uric acid level of <360 µmol/l (<6 mg/dl). Drugs of first choice are xanthine oxidase inhibitors. Achievement of the therapeutic objective should be periodically reviewed, adjusting therapy as necessary.

Efficacy and safety of febuxostat for treatment of asymptomatic hyperuricemia among kidney transplant patients: A meta‐analysis of observational studies

The objective of this meta-analysis of observational studies was to evaluatethe efficacy and safety profiles of febuxostat in treating hyperuricemia among kidney transplant patients. We conducted electronic searches in PubMed, Embase, and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify studies that investigated the effects of febuxostat in kidney transplant patients on uric acid as well as safety profiles including estimated glomerular filtration rate (eGFR), hemoglobin level (Hb), white blood cell counts (WBC), liver enzymes, and trough level of tacrolimus. Seven observational studies with 367 participants were included in this meta-analysis. Compared with allopurinol, the febuxostat group demonstrated a higher odds of achieving target uric acid levels lower than 6mg/dL within 12months (OR=2.9, P=.004). However, there was no statistical difference in change of uric acid (WMD=-1.0mg/dL/y, P=.32) and change in allograft eGFR within a year (WMD=0.01mL/min/1.73m2 /y, P=.98) between febuxostat and allopurinol. Regarding safety profiles, there were no statistical differences in eGFR, Hb, WBC, liver enzymes (AST, ALT), and trough level of tacrolimus between baseline and at the study end. Only one study reported suspected graft loss among febuxostat group. Among kidney transplant patients, treating hyperuricemia with febuxostat showed a higher odds of reaching the target of serum uric acid<6mg/dL compared with allopurinol without causing significant side effects including change in tacrolimus level, liver function, decline in renal graft function, and bone marrow function.

Current Possibilities in the Correction of Hyperuricemia in Patients with Urolithiasis and Uric Acid Hypercrystallization

The objective: to study the effectiveness of the reception and the peculiarities of the use of the drug febuxostat in the correction of the level of uric acid (UA) in the blood serum of patients with urolithiasis and uric acid (UA) hypercrystalluria compared with allopurinol.Materials and methods. The study involved 310 patients with urolithiasis and UAH in whom hyperuricemia was detected. Patients of the 1st group (n = 124) took febuxostat, the 2nd group (n = 186) took allopurinol. Monitoring the level of UA in blood serum and urine was performed 1 time per month for the first 3 months and 1 time in 2 months for the next 10 months.Results. Depending on the speed of reaching the target level of serum UA in the course of treatment with both drugs, three groups were identified: a – 106 (36.3%) patients with fast achievement of the target level of UA in serum (in the first 2 months); b – 100 (35.2%) patients with a significant decrease in uricemia in the first 2 months and a long time to reach the target UA values in blood serum (more than 4 months); s – 86 (29.3%) patients with severe correction of hyperuricemia (more than 6 months). The use of febuxostat makes it possible to achieve the target serum UA level faster and safer than allopurinol – after 4 months in 102 (82.3%) patients of the 1-st group compared with 61 (36.2%) patients of the 2nd group. The absolute values of the level of UA in plasma are not decisive in the choice of the initial dose of febuxostat. The criterion for the safe transfer of patients to maintenance doses of uricostatic drugs is the normalization of UA levels not only in blood serum, but also in urine. The use of febuxostat and allopurinol preparations requires an individual selection of therapeutic and maintenance doses, based on dynamic control of the level of UA in the blood serum and urine during treatment for a long period of time. A significant increase in the level of daily diuresis while taking both uricostatic drugs may indicate an improvement in renal function and also the possibility of restoring the functional state of the tubular apparatus against the background of an adequate correction of hyperuricemia, the possibility of reverse changes caused by urate nephropathy is more pronounced while taking febuxostat.Conclusion. Febuxostat is a modern powerful uricostatic drug with a selective mechanism of action and better efficacy (93.5% in the 1st group compared to 78.1% of the patients in the 2nd group), as well as tolerance than allopurinol (side effects in 9, 6% of patients). The inclusion of febuxostat in the complex of measures for prophylactic and metaphylaxis of urolithiasis for faster and safer correction of hyperuricemia will make it possible to increase their effectiveness.

Failure to reach uric acid target of

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from...

Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort

BackgroundLow doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs.MethodsTo compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software.ResultsTwo hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 μmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 μmol/L vs. Ben 35.7% and 163.99 μmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 μmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min−1 1.73 m−2 at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%).ConclusionOverall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 μmol/L or Ccr ≤ 110 mL min−1 1.73 m−2 at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients.Trial registrationRegistered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).

Evaluation of the state of medical care in patients with arterial hypertension in combination with gout by retrospective analysis data.

The prevalence of cardiovascular diseases, especially arterial hypertension, continues to increase. An important problem is the management of the patient with a comorbid pathology in the primary link by the family physician. The purpose of this study was to assess the state of medical care in patients with arterial hypertension combined with gout, using a retrospective analysis of ambulatory cards, diagnostic and treatment data. There were analyzed 105 outpatient cards that met the inclusion criteria. The mean age of patients was 53.5±10.2 years. Among the examined patients there were 99 males (94.3%), and 6 (5.7%)females. Аrterial hypertension stage II has been reported in 100 (95.2%) patients, stage III – 5 (4.8%) patients. Аrterial hypertension 1 degree is established in 74 (70,5%) patients, 2 degrees – 21 (20%), 3 degrees – 10 (9,5%). The average duration of the gout was 4.4 [4; 2] years, arterial hypertension – 5.3 [3; 1] years. Acute gouty arthritis was present in 11 (10.5%) patients, chronic gouty arthritis – 85 (81%), and chronic tofi arthritis – 9 (8.5%). Patients seek medical help from their family doctor too late. Examination of patients with hypertension in combination with gout is not complete, this contributes to underestimation of total cardiovascular risk. In a number of cases, titration of the dose of allopurinol higher than 300 mg is not, performed so only a third of patients reach the target uric acid level.

The current treatment strategy for gouty arthritis

Febuxostat is a non-purine selective inhibitor of isoforms of xanthine oxidoreductase (XOR), the effect of which is aimed at lowering the level of serum uric acid (UA). Febuxostat is a more potent inhibitor of XOR than allopurinol, as confirmed by that target UA levels have been achieved more frequently with febuxostat than with allopurinol, particularly in patients with high serum urate concentrations. The pharmacokinetic properties of febuxostat are not dependent on renal clearance, which distinguishes it from allopurinol and may benefit patients with chronic kidney disease. A number of studies are being conducted to further evaluate the cardiovascular safety of febuxostat and its possible positive effects in preserving renal function. Of importance is the fact that febuxostat does not require dose adjustment in elderly patients.

The effects of xanthine oxidase inhibitor in patients with chronic heart failure complicated with hyperuricemia: a prospective randomized controlled clinical trial of topiroxostat vs allopurinol\u2014study protocol

BackgroundHyperuricemia has a close relationship with cardiovascular diseases including heart failure. However, it is controversial whether xanthine oxidase inhibition has benefits for patients with chronic heart failure. We designed the Effect of Xanthine Oxidase Inhibitor in Chronic Heart Failure Patients Complicated with Hyperuricemia study (Excited-UA study) to compare the beneficial effects between a novel xanthine oxidoreductase inhibitor, topiroxostat, and a conventional agent, allopurinol, in patients with chronic heart failure and hyperuricemia. We focus on serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiography-based cardiac function, vascular endothelial function, renal function, inflammation, and oxidative stress.MethodsThe excited-UA is a prospective, randomized, open-label, blinded-endpoint clinical trial designed to prove our hypothesis that topiroxostat is more effective than allopurinol in patients with chronic heart failure and hyperuricemia. A total of 140 patients with chronic heart failure and hyperuricemia (plasma brain natriuretic peptide level ≥ 40 pg/mL and serum uric acid level ≥ 7.0 mg/dL) are randomly assigned (ratio 1:1) into either the topiroxostat group (40–160 mg/day) or allopurinol group (100–300 mg/day), to achieve the target uric acid level of 6.0 mg/dL. According to the protocol, all patients are followed up annually for 24 weeks. The primary endpoint is percent change in serum NT-proBNP level at 24 weeks from baseline.ConclusionsThe Excited-UA study would provide novel evidence for the clinical relevancy of xanthine oxidoreductase inhibitor treatment in patients with chronic heart failure and hyperuricemia.

English

Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR). Its pharmacokinetics is not dependent on renal clearance, and it may be advantageous in patients with chronic kidney disease (CKD). Although febuxostat is effective in patients with mild-to-moderate CKD, its efficacy and safety in patients with severe CKD remain unclear. This retrospective study included patients with an estimated glomerular filtration rate (eGFR) of < 30 ml/min/1.73 m2 and hyperuricemia, who received febuxostat. The study was performed at Kaohsiung Medical University Hospital between January, 2015 and December, 2015. Changes were observed in the serum uric acid level, rate of achieving the target uric acid level (<6.0 mg/dL), changes in the eGFR, treatment dosage, and adverse events. 217 patients (65.9 ± 15.1 yrs, 145 males and 72 females) with severe CKD and hyperuricemia were included. Febuxostat significantly lowered the serum uric acid level (9.4 ± 1.9 at baseline and 5.6 ± 1.9 ml/min after treatment, P < 0.001). The serum uric acid level was <6 mg/dl in 126 patients (58.1%). There were no significant changes in eGFR (17.6 ± 7.4 at baseline and 17.8 ± 8.9 ml/min after treatment, P = 0.642) or indices of liver dysfunction. Adverse events were found in 5 patients, all adverse events improved after discontinuing febuxostat. This study demonstrated that febuxostat is efficacious and well tolerated in severe CKD patients with hyperuricemia, although renal function monitoring may be needed. Key words: Febuxostat, hyperuricemia, renal insufficiency, chronic.

Time to Target Uric Acid to Retard Chronic Kidney Disease Progression.

Uric acid (UA) remains a risk factor for the progression of chronic kidney disease (CKD). Most observational studies showed a slight elevation in the serum UA level and this independently predicts the incidence and development of CKD. The recent meta-analysis, however, did not reach the conclusion that urate-lowering therapy with allopurinol retards the progression of CKD. The target level of serum UA if treated is another issue of debate. Our recent analysis by propensity score analysis has shown that the serum UA should be targeted below 6.0 mg/dL to inhibit the progression towards end-stage renal disease. Underlying mechanisms whereby an increase in serum UA induces kidney injury have been elucidated in animal models. Hyperuricemic models can lead to systemic hypertension, arteriolosclerosis including afferent arteriolopathy as well as albuminuria probably due to the activation of oxidative stress. Discoveries of urate transporters have elucidated the novel mechanism of UA transport in the kidney and intestine. The intestinal ABCG2 may play a compensatory role in light of decreased renal clearance of UA in CKD model rats, the trigger of which is not a uremic toxin but serum UA itself. Insulin directly upregulates URAT1 and downregulates ABCG2 in the kidney tubules, suggesting a possible link between UA and metabolic syndrome. This review summarizes the recent knowledge on the causal effect of serum UA on the kidney injury.

Uric Acid: The Lower the Better?

Uric acid (UA) is still considered a risk factor, or even a causative agent, for chronic kidney disease (CKD); however, a few, important, clinical questions remain unanswered; in particular: when and whether urate-lowering therapy should be commenced in subjects with asymptomatic hyperuricemia and/or monosodium urate crystals deposition? What is the most appropriate UA target to be achieved and how long does it need to be maintained? How does treatment need be adjusted in patients with chronic kidney disease? The observational and intervention studies available do not fully answer such questions, and a treatment to target trial is required. We provide here some preliminary opinion on how such a trial might be designed. A final unresolved issue relates to the possible (if any) dangers of overtreatment of hyperuricemia, leading to "hypouricemia," which may occur more frequently with newer, more potent, drugs. A U- or J-shaped association has been found between UA levels and mortality in epidemiologic studies; patients with congenital hypouricemia are more prone to exercise-induced renal failure; a theoretical concern, linked to more complete Xanthine Oxidase inhibition, may involve xanthine nephropathy, although up to now, it has been observed almost exclusively in patients with tumor lysis syndrome. Key Messages: Although there is no definite answer to the title question at the moment, available information tends to indicate a treatment target with serum UA levels between 5.0 and 6.0 mg/dL as reasonable.

A rationally grounded approach to treating gout with regard to its onset and course and the presence of comorbidity according to the European League against Rheumatism (EULAR 2016) recommendations

The review analyzes in detail the management of gout, which takes into account its onset and course and the presence of comorbidity. Emphasis is placed on drug and non-drug treatments and urate-lowering therapy in patients with kidney dysfunction. Along with allopurinol, the urate-lowering drug febuxostat is first recommended in Russia. The purpose of this review is to notify physicians of the possibility of achieving the target uric acid levels when treating gout with hyperuricemia.