Target Serum Uric Acid Levels Research Articles

Adherence and Treat-to-Target Benchmarks in Older Adults With Gout Initiating Urate-Lowering Therapy in Ontario, Canada: A Population-Based Study.

We sought to evaluate urate-lowering therapy (ULT) adherence and treatment-to-target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT. We performed a population-based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels. Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P < 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10-25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89-5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14-2.99), colchicine/oral glucocorticoids co-prescription (OR 1.24, 95% CI 1.14-1.34), and ULT prescription from a rheumatologist. Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps.

Knowledge, Attitudes, and Practices about Hyperuricemia and Gout in Community Health Workers and Patients with Diabetes.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA

BackgroundWe investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients.MethodsThis was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment.ResultsThree hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups.ConclusionThis study did not reveal the benefit of Intensive ULT to improve albuminuria levels.(UMIN000026741 and jRCTs051180146).

Inhibition of the Progression of Chronic Kidney Disease With Hyperuricemia

The final product of the catabolism of purine compounds in humans is uric acid (UA), which is a weak organic acid, over 98% of which is ionized into monosodium urate. UA is excreted by the kidneys, approximately 80-99% is reabsorbed in the proximal tubules of the kidneys. About 20% of UA is excreted through the intestine, where it is destroyed by microflora to carbon dioxide and water. The reference value of UA in blood plasma is 6.5-7 mg/dl in men and 6–6.5 mg/dl in women. The content of UA in the range of 360-400 μmol/l or 6-6.8 mg / dl increases the risk of crystallization under physiological conditions, and regardless of gender. UA levels greater than 7.0 mg/dl are associated with an increased risk of developing gout or nephrolithiasis. Hyperuricemia may occur due to increased production and / or decreased renal excretion of UA. Hyperuricemia is high in the general population and is associated with the development and progression of chronic kidney disease (CKD). Currently, allopurinol and febuxostat are used to correct hyperuricemia. The use of allopurinol should begin with a low dose (50-100 mg/day) and gradually titrate until the target level of UA in the blood is reached or until it is reached to the maximum. If necessary, the dose of allopurinol is increased by 100 mg every 2–4 weeks until the target serum UA level is reached. According to EULAR's recommendations for the treatment of gout, if the target level of UA cannot be achieved with an adequate dose of allopurinol, it should be replaced with febuxostat or uricosuric or a combination of febucostat with uricosuric. Febuxostat is also indicated for allopurinol intolerance. Febuxostat in doses of 80 and 120 mg/day was more effective than allopurinol at a dose of 300 mg/day. With CKD with mild or moderate renal failure, as well as in the elderly, it is not necessary to adjust the dose of febuxostat. The likelihood of reaching the target level of UA in the blood with reduced kidney function is higher in febuxostat. If the patient does not have serious cardiovascular diseases, the patient can be transferred to febuxostat, starting with a dose of 40 mg/day, and gradually titrated, especially in the case of CKD.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

COMPARISON BETWEEN RENOPROTECTIVE EFFECTS OF FEBUXOSTAT AND ALLOPURINOL IN CHRONIC KIDNEY DISEASE PATIENTS WITH HYPERURICEMIA

Objective: The objective of the study was to compare the renoprotective effects of febuxostat versus allopurinol in chronic kidney disease patients with hyperuricemia. Methods: One hundred and ten patients were divided randomly into two equal groups: group F (febuxostat) and group A (allopurinol). Group F patients received tablet febuxostat 40 mg OD for 4 months and group A patients received tablet allopurinol 100 mg TDS for 4 months. Following parameters such as estimated glomerular filtration (eGFR) assessment, serum creatinine, serum uric acid (SUA), total serum protein, urine creatinine, urine protein, blood urea, and number of dialysis were carried out and repeated at the end of 1st–4th month to check for the effect of the test drugs on the status of kidney function. Observations: Febuxostat caused more rise in eGFR than allopurinol. Meanwhile, the number of patients with eGFR ≤15/mL/min/1.73 m2 showed no difference between the groups. No patient showed &gt;10% decrease in the eGFR values. Febuxostat showed more decline in SUA levels than allopurinol, although the number of patients reaching the target SUA levels was the same in both groups. Febuxostat led to a more reduction in serum creatinine levels than allopurinol. Urine creatinine and urine albumin levels decline were associated more with febuxostat. No remarkable difference in comparison of both the groups in terms of total serum protein and serum globulin, although a significant rise was seen with febuxostat in serum albumin levels. Both drugs had a similar sequel in declining blood urea nitrogen levels. No discernible difference in the number of dialysis sessions needed by patients in the previous month was seen in the study groups. Conclusion: The present study concluded that febuxostat appears to be a better alternative to allopurinol for chronic kidney disease patients with hyperuricemia. Febuxostat has a superior renoprotective effect than allopurinol.

Hyperuricemia, gout and comorbidity

Hyperuricemia is most often combined with lipid metabolism disorders, modifiable risk factors for coronary heart disease, stroke, abdominal obesity, type 2 diabetes mellitus, arterial hypertension, urolithiasis, chronic kidney disease. Current data indicate the presence of pro-inflammatory, pro-oxidant and vasoconstrictive effects of uric acid, which may contribute to the development of cardiometabolic disorders. Normal serum uric acid levels are &lt;6 mg / dl (&lt;360 mmol / l) for women and &lt;7 mg / dl (&lt;420 mmol / l) for men. Currently, the role of hyperuricemia as an independent biomarker of the risk of cardiovascular events is emphasized. Both gout and subclinical hyperuricemia are associated with unfavorable cardiovascular outcomes. Patients should be informed about the risk factors of hyperuricemia; the need for lifestyle modification, diet compliance, and correction of drug therapy for comorbid conditions. According to international and domestic recommendations, urate-lowering therapy is indicated for asymptomatic hyperuricemia (&gt;360 mmol / l) and high cardiovascular risk. The data available today allow us to consider the target serum uric acid level &lt;5 mg / dl (&lt;300 mmol / l) for patients with high cardiovascular risk, including at least 2 of the following risk factors: hypertension, diabetes mellitus, dyslipidemia, stroke, heart attack, chronic disease kidneys, and &lt;6 mg / dl for patients who do not have these risk factors. The urate-lowering drug is selected taking into account the concomitant pathology and the presence or absence of liver or kidney dysfunction. Xanthine oxidase inhibitors are still the first-line drugs for the correction of hyperuricemia. The superiority of xanthine oxidase inhibitors is due to the potential inhibition of the production of reactive oxygen species and their antioxidant effect. Treatment of gout is aimed at achieving clinical improvement in acute and chronic arthritis, preventing recurrence of arthritis and damage to internal organs, as well as reducing the risks of negative effects on comorbid pathology. Clinicians are faced with the task of controlling cardiovascular diseases in patients with asymptomatic hyperuricemia and gout. Further studies are needed to investigate the relationship between gout, hyperuricemia and increased risk of cardiovascular diseases, as well as to establish a more complete picture of the prevalence of a wide range of comorbid conditions.

Odds of Achieving Target Serum Uric Acid Levels Among Gout Patients: The Role of Rurality in Outcomes and Treatment Adherence.

The goal of this paper was to analyze patient outcomes related to gout treatment including, serum uric acid (sUA) measures and treatment adherence across patients in metropolitan, micropolitan or rural counties. We conducted a drug-disease cohort study among patients with gout initiating urate lowering therapy. The proportion of patients with sUA < 6 mg/dL at 1 year of follow-up is compared over the cohort groups using a chi-square test and adjusted logistic regression. Adherence to urate lowering therapy was calculated using the proportion of days covered (PDC). A T-test was used to compare the average PDC and an adjusted logistic regression model was used to estimate the odds of a PDC greater than 80%. A total of 9922 patients were included in the study. Most patients were in a metropolitan (77.4%) area, followed by micropolitan (11.8%) and finally, (10.8%) in a rural area. We found no statistically significant difference among the proportion of patients achieving target sUA of <6 mg/dL, 37.17% among metropolitan patients, 38.9% among micropolitan patients, and 37.7% for those in a rural area, P-value = .502. The proportion of patients achieving 80% treatment adherence was 49.92% in the metropolitan, 51.78% in the micropolitan, and 55.05% in the rural areas, P-value = .005. Adjusted regression models showed no statistically significant difference in proportions achieving target sUA levels or 80% adherence. Urban patients treated for gout did not have better gout outcomes compared to rural patients. Future research should consider provider-based interventions to improve outcomes.

Considerations for Choosing First-Line Urate-Lowering Treatment in Older Patients with Comorbid Conditions.

Gout is the most common inflammatory arthritis in adults. The prevalence of gout increases with age. Urate-lowering treatment (ULT) among older patients is often challenging in that patients frequently suffer insufficient effectiveness or adverse events due to comorbidities, concurrentmedications, and altered pharmacokinetics. The large-scale randomized controlled trials (RCTs) directly investigating gout patients regarding cardiovascular (CV) safety have only recently been introduced; CARES and FAST compared the CV safety of the two xanthine oxidase inhibitors (XOis), febuxostat versus allopurinol, in patients with gout. Based on the CARES trial that showed CV concerns with febuxostat, the current international guidelines recommend allopurinol as first-line ULT in gout, while preserving other agents as a second-line treatment, despite a higher potency of febuxostat. XOis would be more suitable than uricosurics to treat older patients with gout due to the high prevalence of chronic kidney disease (CKD) in older patients. However, allopurinol alone might not achieve the target serum uric acid levels below 6 mg/dL and CKD might confer an increased risk of allopurinol induced cutaneous adverse reactions in older patients. Furthermore, as well as the later analysis of CARES participants who were lost to follow-up, data from the FAST trial and real-world studies suggest non-inferior CV safety for febuxostat compared to allopurinol even in the presence of CV diseases. Thus, febuxostat use in older patients with renal impairment may be more positively considered. The combination therapy of a novel uricosuric, verinurad, plus febuxostat reduced albuminuria in hyperuricemic patients with type 2 diabetes and CKD in a phase 2a trial, and further RCTs are awaited. Finally, the sodium-glucose cotransporter-2 inhibitor class of oral hypoglycemic agents, known to exert beneficial CV and renal effects independent of glycemic control, have shown a uricosuric effect and could be used as adjunctive therapy in older patients with cardiorenal comorbidities.

Эффективность фебуксостата у пациентов с подагрой в зависимости от функции почек

Aim: to determine the probability of achieving the target serum uric acid (UA) level during therapy with febuxostat (in the tablet form) in patients with gout stratified depending on kidney function, including patients with type 2 diabetes mellitus (DM2). Patients and Methods: the study included patients over 18 years of age with gout who had not previously taken febuxostat or other urate- lowering drugs for at least 2 weeks before inclusion, with a serum UA level &gt;360 μmoL/L. All were prescribed with febuxostat in the tablet form 80 mg/day. If the target serum UA level was not reached (&lt;360 μmoL/L), the dosage level was increased up to 120 mg/day. Laboratory tests included the determination of blood glucose, creatinine, UA. Initially, patients were divided into groups according to chronic kidney disease (CKD) stages by the level of estimated glomerular filtration rate (eGFR) by CKD-EPI: C1 — high or optimal renal function (&gt;90 mL/min/1.73 m2), C2 — slightly reduced renal function (60–89 mL/min/1.73 m2), C3 — moderately/considerably reduced renal function (30–59 mL/ min/1.73 m2), C4 — significantly reduced renal function (15–29 mL/min/1.73 m2). Patients with DM2 were analyzed separately. The follow-up period covered at least 26 weeks: the primary endpoint was to achieve the target serum UA level, and the eGFR tendency was also evaluated.Results: 136 patients with gout were examined. DM2 was in 38 (27.9%) patients. CKD C0–1 was detected in 30 (22.1%) patients, C2 — in 28 (20.6%), C3 — in 62 (45.6%), C4 — in 16 (11.8%). Febuxostat (in the tablet form) was received at a dose of 80 mg/day in 98 (72.1%) patients, 120 mg/day in 38 (27.9%) patients. There was the following preventive administration of anti-inflammatory therapy: colchicine — 59 (43.4%) patients, NSAIDs — 51 (37.5%) patients, glucocorticosteroids — 12 (8.8%) patients, no drug therapy — 14 (10.3%) patients. UA level significantly decreased in all groups, the average value of Δ MK and the frequency of achieving the target serum UA level were comparable. Achievement of the target serum UA level in general was in 84% of patients; in C0–1, C2, C3, C4 — in 83, 89, 82 and 81% of patients, respectively. The mean eGFR values relative to the baseline increased by the end of the study in all groups, but significant differences were only in patients with C0–1: 101.3±18.1 mL/min/1.73 m2 vs 102.8±28.6 mL/min/1.73 m2 (p=0.002). Of the 38 patients with DM2, 33 (87%) achieved the target serum UA level. In 2 patients with CKD C3, ALT and AST increased up to two norms (when taking febuxostat 120 mg/day). Conclusion: the possibility of achieving the target serum UA level when taking febuxostat (in the tablet form) in patients with gout does not depend on kidney function, including in patients with DM2. KEYWORDS: gout, febuxostat, glomerular filtration rate, chronic kidney disease, diabetes mellitus. FOR CITATION: Eliseev M.S., Zhelyabina O.V., Chikina M.N., Thakokov M.M. Febuxostat efficacy in patients with gout depending on kidney function. Russian Medical Inquiry. 2022;6(3):140–147 (in Russ.). DOI: 10.32364/2587-6821-2022-6-3-140-147.

Association of the Q141K polymorphism of the ABCG2 gene with the effectiveness of urate-lowering therapy in patients with gout (a pilot study)

Achieving the target serum uric acid (UA) level is a priority in the treatment of gout.Objective: to study the relationship of the ABCG2 gene polymorphism (rs2231142) with the efficacy of allopurinol and febuxostat in patients with gout.Patients and methods. The study included 82 patients with gout over 18 years of age with serum UA level &gt;360 μmol/L who did not take uratelowering therapy.All patients were prescribed allopurinol 100 mg daily, followed by its titration until the target UA level was reached (&lt;360 μmol/L or &lt;300 μmol/L in patients with chronic tofus gout), up to a maximum of 900 mg/day, in patients with glomerular filtration rate &lt;60 ml/min/1.73 m2 – up to 300 mg/day. Patients who did not reach the target UA level when using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Monitoring of each patient was continued until the target serum UA level was reached.All patients underwent genotyping of the C&gt;A polymorphism (rs2231142) of the ABCG2 gene. We compared the probability of achieving the target UA level, the mean values of a decrease in the serum UA level, and the mean doses of urate-lowering drugs in patients with different genotypes (CC, CA, AA) of the ABCG2 gene.Results and discussion. The target UA level in 45 (55%) of 82 patients was defined as &lt;300 μmol/L, in the remaining 37 – as &lt;360 μmol/L.In 26 patients, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) patients treated with allopurinol, the target UA level was achieved, in the remaining 54 (66%) patients, allopurinol was substituted by febuxostat, and in 22 (41%) of them the UA level decreased and was below the target.The CC genotype of the ABCG2 gene was detected in 51 (62%) patients, the CA genotype in 30 (37%) and the minor genotype AA in 1 (1%).The probability of achieving the target UA level during therapy with allopurinol in carriers of homozygous CC genotype and genotypes CA or AA did not differ: 17 (33%) and 11 (35%) cases, respectively, but patients with CA and AA genotypes required a significantly higher dose of allopurinol (365±102 mg/day) than patients with the CC genotype (290±85 mg/day), p=0.002. Of the 54 patients who took febuxostat and did not reach the target UA level, 30 (56%) had the CC genotype and 24 (44%) had the CA genotype, the probability of reaching the target UA level was also comparable (p=0.22).Conclusion. The probability of reaching the target serum UA level in patients with gout taking allopurinol is not associated with the C&gt;A polymorphism of the ABCG2 gene, but the presence of CA and AA genotypes is identified with a higher dose of the drug. The C&gt;A (rs2231142) polymorphism of the ABCG2 gene does not affect the ability to achieve the goal of therapy when using febuxostat in patients with allopurinol ineffectiveness.

Uric acid-lowering effect of dotinurad, a novel selective urate reabsorption inhibitor, in hypertensive patients with gout or asymptomatic hyperuricemia: a pooled analysis of individual participant data in phase II and III trials

ABSTRACT Background: Hyperuricemia is a risk factor for the development of hypertension and is comorbid in many hypertensive patients. According to Japanese hypertension management guidelines published in 2019, a target serum uric acid level of ≤6.0 mg/dL is recommended in hypertensive patients with gout or asymptomatic hyperuricemia. Dotinurad is a novel uric acid-lowering drug classified as a selective urate reabsorption inhibitor. A pooled analysis was performed on the uric acid-lowering effect of dotinurad in 222 hypertensive patients with gout or asymptomatic hyperuricemia in four clinical trials (NCT02344862, NCT02416167, NCT03100318, NCT03372200). Moreover, we analyzed the long-term uric acid-lowering effect of dotinurad in 154 hypertensive patients with gout or asymptomatic hyperuricemia (NCT03006445). Results: In the pooled analysis, the percent change in the decrease of serum uric acid with the use of dotinurad was 42.17 ± 12.42% at a dose of 2 mg and 60.42 ± 8.03% at a dose of 4 mg; the percentage of patients who achieved a serum uric acid level of ≤6.0 mg/dL was 82.8% and 100.0%. The long-term uric acid-lowering effect of dotinurad showed almost the same results. In this study, the concomitant use of diuretics or angiotensin II receptor blockers affected the uric acid-lowering effect of dotinurad at only a dose of 2 mg in the pooled analysis. Conclusions: In the pooled analysis, dotinurad lowered serum uric acid levels. Dotinurad has an achievement rate of over 80% for serum uric acid level of ≤6.0 mg/dL in both analyses, and will be clinically useful for the management of hyperuricemic states in hypertensive patients.

Serum uric acid control for prevention of gout flare in patients with asymptomatic hyperuricaemia: a retrospective cohort study of health insurance claims and medical check-up data in Japan

ObjectivesIn patients with gout, treating to target serum uric acid levels (sUA) of ≤6.0 mg/dL is universally recommended to prevent gout flare. However, there is no consensus on asymptomatic hyperuricaemia....

How much does fat mass change affect serum uric acid levels among apparently clinically healthy Korean men?

Objective:The aim of this study was to examine the impact of fat mass alteration on serum uric acid (SUA) levels in apparently clinically healthy men.Methods:We evaluated 27,387 men who consecutively underwent health check ups between 2015 and 2017. We assessed the likelihood of achieving a SUA level of <0.41 mmol/L and compared the SUA levels according to fat mass changes.Results:Compared with those without fat mass change (the reference group), the odds ratios (95% confidence interval) of achieving a SUA level of <0.41 mmol/L for fat mass decreases of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg were 1.63 (1.45–1.82), 1.19 (1.06–1.34), and 1.07 (0.97–1.18), respectively, while those for a fat mass increase of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg were 0.71 (0.64–0.78), 0.87 (0.79–0.97), and 0.95 (0.86–1.04), respectively. The corresponding beta-coefficients of SUA levels (mmol/L) were –0.26 [–0.29–(–0.23)], –0.12 [–0.16–(–0.09)], and –0.09 [–0.12–(–0.06)] for fat mass decreases of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg, respectively. Every 1-kg fat mass reduction was associated with 9% increased odds of achieving the target SUA level. The multivariate SUA level difference per 1-kg fat mass gain was 2.97 µmol/L. Similar levels of association persisted among the prespecified subgroups.Conclusion:We quantitatively demonstrated that fat mass reduction contributes to a clinically relevant decrease in SUA levels and a significant increase in the likelihood of achieving target SUA levels. Our findings may help to provide clear clinical guidance on fat mass alteration to reduce SUA levels in patients with hyperuricemia.

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 (&lt;360 μmol/L) for all patients or &lt;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.

Factors associated with achieving target serum uric acid level and occurrence of gouty arthritis: A retrospective observational study of Japanese health insurance claims data.

PurposeThis study assessed factors associated with achieving target serum uric acid (sUA) level and occurrence of gouty arthritis in Japanese clinical practice.MethodsJapanese health insurance claims and medical check‐up data from October 2015 to March 2017 were analyzed to assess factors associated with target sUA achievement in gout and asymptomatic hyperuricemia and gouty arthritis in gout. Target sUA was further assessed by subgroup analysis of urate‐lowering therapy (ULT) prescriptions and outcomes, stratified by renal function.ResultsPatients achieving target sUA tended toward older, female, higher ULT dose, higher adherence, more comorbidities, and/or antidiabetic drugs prescribed. Renal dysfunction and/or diuretic prescriptions were associated with reduced achievement of target sUA. Severe renal dysfunction was particularly influential (odds ratio [OR] = 0.22 [95% confidence interval (CI): 0.10‐0.48] for <15, 0.15 [0.10‐0.23] for ≥15 to <30, compared with eGFR ≥90 mL/min/1.73 m2). Across all renal function categories, mean prescribed ULT dose was low (febuxostat 17.0‐21.0 mg/day, allopurinol 123.1‐139.6 mg/day), and target sUA achievement was reduced among renal dysfunction patients. Gouty arthritis was more likely in patients with a prior history of such occurrences, and less likely for higher ULT adherence, sUA monitored regularly at medical facilities, and/or more comorbidities.ConclusionIn a real‐world setting, severe renal dysfunction is the most important risk factor for failure to achieve the target sUA, suggesting suboptimal disease management in patients with gout or hyperuricemia complicated by this condition. Findings associated with gouty arthritis suggest that these occurrences could be successfully managed by regular monitoring of sUA and closer adherence to ULT.

Achievement of the target serum urate level among patients with gout treated with allopurinol or febuxostat in an arthritis clinic in the Philippines

Objective Gout is an important cause of disability among Filipinos, despite measures for effective management. This study aims to determine attainment of target serum uric acid level (SUA ≤ 6 mg/dl) among patients with gout given urate-lowering therapy (ULT) over 6–12 months. Methods This is a single-center, prospective cohort study conducted in one adult Arthritis Clinic at the University of the Philippines-Philippine General Hospital which included 138 patients with gout (1977 ACR criteria), SUA ≥ 6 mg/dl prior to ULT, initiated on ULT (allopurinol or febuxostat), with six months minimum follow-up and with SUA determination post-treatment. Results 37.7% (52/138) and 36.2% (50/138), achieved target SUA at 6 and 12 months. The factors associated with achieving target SUA in 6 months are BMI > 25 kg/m2 [OR 6.98, 95% confidence interval (CI) 1.44–33.88, p value = .016], allopurinol dose ≥ 300 mg (OR 15.76, 95% CI 2.24–111.06, p value = .006), and baseline SUA (OR 0.52, 95% CI 0.33–0.82, p value = .005). The factors associated with achieving target SUA in 12 months are employment (OR 5.51, 95% CI 1.00–30.33, p value = .050), baseline SUA (OR 0.45, 95% CI 0.28–0.74, p value = .002), and age at onset of gout (OR 1.08, 95% CI 1.01–1.15, p value = .026). Conclusion Target SUA level was not achieved at 6 and 12 months of ULT in most of this cohort. This mirrors the deficient control of gout and should urge health professionals to fully study and address the problem.

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.

Physicians' perceptions of asymptomatic hyperuricemia in patients with chronic kidney disease: A questionnaire survey.

BackgroundHyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients.MethodsQuestionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology.ResultsA total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines).ConclusionMost Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.

Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements

ObjectivesDespite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout...