A 50-year-old woman who had been abusing of furosemide and torasemide for 8 years because of edema during menstruation, had hyperuricemia (11-13 mg / dL), and showed repeated episodes of gout flare. Abdominal ultrasonography revealed gouty kidney-like findings (hyperechoic medulla). Of the 5208 abdominal ultrasonographies performed for patients with gout or hyperuricemia during the five years from 2017 to 2021, only 22 cases showed hyperechoic medulla findings; therefore, hyperechoic medulla findings are considered to be rare. We reviewed the findings of abdominal ultrasonography performed multiple times for 11 patients who had been treated with uric acid-lowering drugs for 5 years or more. As a result, no improvement in hyperechoic medulla findings was observed. These results contradicted a report from Vietnam stating that hyperechoic medulla findings were improved in 36% of 502 patients with severe gout by uric acid-lowering treatment. Therefore, we consider that it is necessary to clarify whether hyperechoic medulla findings in patients with gout and hyperuricemia are due to reversible urate crystal deposition or irreversible renal medulla substrate changes.

Uric acid levels are much lower in women than men, mainly due to differences in excretion caused by female hormones. It is known that the difference in uric acid levels between men and women becomes smaller after reaching 50 years old, when the influence of female hormones decreases significantly. In this study, we collected and compared data on sex differences in uric acid excretion in men over 50 years old (male group, n=26) and postmenopausal women (female group, n=31). As the results, the significant difference in serum uric acid levels between men and women disappeared in this age group (male group: 5.3±1.1 mg/dL, female group: 4.8±1.2 mg/dL, p=0.110), and uric acid excretion was significantly higher in women even after menopause (uric acid/creatinine ratio: male group: 0.47±0.13, female group: 0.69±0.23, p<0.001; FEUA: 7.7±2.6% in the male group and 9.7±3.2% in the female group, p=0.018). Uric acid excretion was positively correlated with estimated salt intake in both men and women (uric acid/creatinine ratio and estimated salt intake: men R²:0.485, p<0.001, women R²:0.521, p<0.001), but this was stronger in women. In postmenopausal women, salt intake accelerated uric acid excretion and, in some cases, increased the risk of cardiovascular events even with low serum uric acid levels. This may be one of the possible reasons to explain the phenomenon that uric acid levels, which indicate the risk of cardiovascular events, are lower in women than men.

The coronavirus disease (COVID-19) vaccine markedly contributes to the prevention of infection and aggravation of COVID-19, which has spread throughout the world, but many vaccinated people suffer from various local or systemic adverse events. In October 2021, a questionnaire survey was conducted involving outpatients with gout to examine the association between COVID-19 vaccination and gout flare. Of the 1,480 vaccinated gout patients, 20 (1.35%) had gout flare within 3 days of vaccination. There was no difference depending on the type of vaccine, Pfizer or Moderna. Thirteen patients were being treated with uric acid-lowering drugs, and 10 of them showed generally good control of serum uric acid levels. In addition to the responses to the questionnaire survey, considering the contents described in the medical records, it was determined that 57 patients (3.85%) were more likely to have gout flare after vaccination. It has been reported that vaccination increases the risk of gout flare, and the suggested mechanism is activation of NLRP3 inflammasomes by the aluminum adjuvant contained in the vaccine preparation, but the COVID-19 vaccine does not contain aluminum adjuvant. Although the pathogenesis of gout flare due to COVID-19 vaccination is unknown, gout flare may be one of the adverse events caused by the COVID-19 vaccine.

A uricosuric drug, which is an inhibitor of urate transporter 1 (URAT1), increases urinary uric acid excretion, leading to a uric acid-lowering effect. The uricosuric drugs probenecid and benzbromarone also inhibit other transporters involved in uric acid transport in addition to URAT1, but dotinurad, which can specifically inhibit URAT1 without affecting other transporters, has come to be used in clinical practice. One hundred and eight gout / hyperuricemia patients who were able to achieve a serum uric acid level of 6 mg / dL or lower by the administration of dotinurad from January to September 2021, were selected as new administration cases. In the same period, 113 patients who changed their treatment from benzbromarone to dotinurad were selected as alteration cases. In both cases, the uric acid control status on dotinurad administration was retrospectively examined. In order to achieve the therapeutic target of a serum uric acid level of 6 mg / dL or lower, the higher the serum uric acid level before administration, the higher the dose of administration. The dose required to achieve the serum uric acid target value was 0.5 mg in 44 cases (40.7%), 1 mg in 40 cases (37.0%), 2 mg in 17 cases (15.7%), 3 mg in 6 cases (5.6%), and 4 mg in 1 case (0.9%), and nearly 80% of patients achieved the target value within a dose of 1 mg. In the alteration cases, the serum uric acid level significantly decreased from 5.7 ± 1.2 to 5.4 ± 1.0 mg / dL. Furthermore, there was a significant decrease from 5.9 ± 1.2 to 5.5 ± 1.1 mg / dL in patients with a decreased renal function (eGFR <60 mL / min / 1.73 m²). These results suggest that dotinurad has a stronger uric acid-lowering effect than benzbromarone, and the effect may be marked in patients with an impaired renal function.

We measured the uric acid / creatinine ratio (UUA / Ucr) and uric acid excretion fraction (FEUA) of spot urine in patients (108 treated with dotinurad, 62 treated with benzbromarone, and 56 treated with febuxostat), when the serum uric acid level was 6 mg / dL or lower. Then, we investigated the differences in UUA / Ucr and FEUA among patients receiving the three drugs. The serum uric acid level and UUA/Ucr and FEUA were 5.3 ± 0.6 mg / dL, 0.504 ± 0.211, and 8.5 ± 4.1% in the dotinurad-treated group (daily dose of 1.1 ± 0.7 mg), 5.0 ± 0.6 mg / dL, 0.541 ± 0.210, and 9.8 ± 3.7% in the benzbromarone-treated group (daily dose of 48.8 ± 22.3 mg), and 5.1 ± 0.7 mg / dL, 0.215 ± 0.079, and 4.0 ± 1.1% in febuxostat-treated group (daily dose of 31.1 ± 13.6 mg), respectively. UUA / Ccr and FEUA were significantly lower in the febuxostat-treated group than in the two uricosuric drug-treated groups. There was a weak positive correlation between drug dose and UUA / Ccr in the dotinurad-treated group, but there was no correlation between drug dose and UUA / Ccr in the benzbromarone-treated group. It is considered that reason why UUA / UCr of patients taking uricosuric drugs as outpatients is not constant may be due to variable intake of food purine. When UUA / gCr corrected with g-creatinine (gCr) is expressed as 24-hour urinary uric acid excretion, there are some patients whose 24-hour urinary uric acid excretion exceeds 800 mg / day, considered to be a risk for urinary stones with uricosuric drugs such as dotinurad and benzbromarone. In the future, it will be necessary to verify the association between uric acid excretion and food purine intake in patients treated with uricosuric drugs, and even if the serum uric acid level is maintained at the target value by the uricosuric drugs, may be necessary to continue dietary treatment including the restriction of food purine intake in consideration of the level of urinary uric acid excretion.

This study examined the association between serum urate levels and food group intake among community-based health checkup participants. The study subjects were 12,443 individuals (5,647 men and 6,796 women; mean age: 63 years) who had completed a short food frequency questionnaire and had serum urate level data from 2009 to 2015. The association between serum urate levels at the time of the health checkup and daily intake (g/day) of 19 food groups based on the Food Intake Frequency Survey was analyzed separately for men and women. The mean serum urate acid level was 5.8±1.3 mg/dL in men and 4.5±1.0 mg/dL in women. Multiple regression analysis adjusted for background factors (age, BMI, and eGFR) revealed that serum urate levels in men showed a significantly positive correlation with alcohol and seafood and a significantly negative correlation with dairy products, bread, rice, and confectionery. In women, serum urate levels showed a significantly positive correlation with seafood and noodles and a significantly negative correlation with soybean and dairy products. Similarly, multivariate logistic regression analysis adjusted for the background factors showed that the odds ratio for hyperuricemia (>7.0 mg/dL) increased with seafood and alcohol and decreased with rice, coffee, bread, and dairy products in men, and decreased with coffee in women. These results suggest that the intake of various food groups is associated with serum urate levels independently of physical factors, and that the association differs in some parts between men and women in community populations.