To describe recent trends in the prevalence of gout and asymptomatic hyperuricemia regarding urate-lowering treatment (ULT) in Japan.
A database of health insurance claims managed by the Japan ...Medical Data Center was used to estimate the annual prevalence of gout and asymptomatic hyperuricemia during 2010-2014. ULT was evaluated for status of the two diseases during the same period. The significance of time trends was evaluated by Cochrane-Armitage trend test.
The prevalence of physician-diagnosed gout in men aged 20-64 years was 1.54% (95% CI: 1.49%-1.58%) in 2010, with a slight but significant (
< 0.001) annual increase, up to 1.66% (95% CI: 1.62%-1.71%) in 2014. In women, gout prevalence was somewhat constant about 0.09% during 2010-2014. Among male patients with gout, 78% received ULT. The prevalence of male patients with asymptomatic hyperuricemia in the same age range, who received ULT, increased significantly from 1.77% (95% CI: 1.72%-1.81%) to 2.14% (95% CI: 2.09%-2.19%) during 2010-2014 (
< 0.001).
Gout prevalence in adult men in Japan has increased significantly in recent years. The prevalence of asymptomatic hyperuricemia under ULT has also increased significantly and was higher than that of gout.
A genetic defect in urate transporter 1 (URAT1) is the major cause of renal hypouricemia (RHUC). Although RHUC is detected using a serum uric acid (UA) concentration <2.0 mg/dL, the relationship ...between the genetic state of URAT1 and serum UA concentration is not clear. Homozygosity and compound heterozygosity with respect to mutant URAT1 alleles are associated with a serum UA concentration of <1.0 mg/dL and are present at a prevalence of ~0.1% in Japan. In heterozygous individuals, the prevalence of a serum UA of 1.1−2.0 mg/dL is much higher in women than in men. The frequency of mutant URAT1 alleles is as high as 3% in the general Japanese population. The expansion of a specific mutant URAT1 allele derived from a single mutant gene that occurred in ancient times is reflected in modern Japan at a high frequency. Similar findings were reported in Roma populations in Europe. These phenomena are thought to reflect the ancient migration history of each ethnic group (founder effects). Exercise-induced acute kidney injury (EI-AKI) is mostly observed in individuals with homozygous/compound heterozygous URAT1 mutation, and laboratory experiments suggested that a high UA load on the renal tubules is a plausible mechanism for EI-AKI.
Renal hypouricemia (RHUC) is a disease caused by dysfunction of renal urate reabsorption transporters; however, diagnostic guidance and guidelines for RHUC have been lacking, partly due to the low ...evidence level of studies on RHUC. This review describes a world-first clinical practice guideline (CPG) and its first version in English for this condition. It was developed following the “MINDS Manual for Guideline Development” methodology, which prioritizes evidence-based medicine. It was published in Japanese in 2017 and later translated into English. The primary goal of this CPG is to clarify the criteria for diagnosing RHUC; another aim is to work towards a consensus on clinical decision-making. One of the CPG’s unique points is that it contains textbook descriptions at the expert consensus level, in addition to two clinical questions and recommendations derived from a systematic review of the literature. The guidance shown in this CPG makes it easy to diagnose RHUC from simple blood and urine tests. This CPG contains almost all of the clinical foci of RHUC: epidemiology, pathophysiology, diagnostic guidance, clinical examinations, differential diagnosis, and complications, including exercise-induced acute kidney injury and urolithiasis. A CPG summary as well as a clinical algorithm to assist healthcare providers with a quick reference and notes from an athlete for both physicians and patients are included. We hope that this CPG will help healthcare providers and patients to make clinical decisions, and that it will promote further research on RHUC.
Increase in the incidence of hyperuricemia associated with gout as well as hypertension, renal diseases and cardiovascular diseases has been a public health concern. We examined the possibility of ...facilitated excretion of uric acid by change in urine pH by managing food materials.
Within the framework of the Japanese government's health promotion program, we made recipes which consist of protein-rich and less vegetable-fruit food materials for H+-load (acid diet) and others composed of less protein but vegetable-fruit rich food materials (alkali diet). Healthy female students were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid and all cations (Na+,K+,Ca(2+),Mg(2+),NH₄+) and anions (Cl⁻,SO₄(2-),PO₄⁻) necessary for the estimation of acid-base balance were measured.
Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated (SO₄(2-) +organic acid-gut alkai) were linearly related with those of the excretion of acid (titratable acidity+ NH4+ - HCO3⁻), indicating that H+ in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, where uric acid excretion increased from 302 mg/day at pH 5.9 to 413 mg/day at pH 6.5, despite the fact that the alkali diet contained a smaller purine load than the acid diet.
We conclude that alkalization of urine by eating nutritionally well-designed food is effective for removing uric acid from the body.
Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood ...triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000–2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic profiles and circulating lymphocytes warrant future longitudinal and molecular mechanistic studies.
Information on the late effects of radiation exposure on atomic bomb survivors is presented. Radiation exposure may cause chronic low-grade inflammation which in turn leads to increased risks of ...contracting cancer, hepatitis, and cardiovascular and autoimmune diseases.
To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer.
A nested case-control study was done in the longitudinal cohort of atomic ...bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose.
H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001, especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers.
A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.
To elucidate the association of serum uric acid concentration with cardiovascular mortality risk.
Serum uric acid level measured from 1966 through 1970 in 10,615 Japanese individuals from a cohort of ...atomic bomb survivors was analyzed for association with subsequent cardiovascular and all-cause mortality until 1999 using the Cox proportional hazard model.
During an average followup of 24.9 years, 5225 deaths occurred, of which 1984 were ascribed to cardiovascular disease. In men, after adjustment for age, elevated serum uric acid level was associated with both cardiovascular and all-cause mortality. After additional adjustment for potential cardiovascular disease risk factors including body mass index, smoking status, alcohol consumption, systolic blood pressure, cholesterol level, and histories of hypertension, diabetes and cardiovascular disease, elevated serum uric acid level in men was associated with all-cause mortality but not with cardiovascular mortality. In women, even after these adjustments, elevated serum uric acid level was significantly associated with cardiovascular and all-cause mortality.
Increased serum uric acid level is a significant and independent risk factor for cardiovascular mortality in women and for all-cause mortality in both men and women.
To examine the role of HLA-DRB1 and tumor necrosis factor (TNF) promoter genotypes in the development and the autoantibody profiles of idiopathic inflammatory myopathy (IIM) in Japanese patients.
...HLA-DRB1 and TNF promoter genotypes were determined, and serum antinuclear autoantibodies were identified in 120 adult Japanese patients with IIM 72 with dermatomyositis (DM), 30 with polymyositis (PM), 18 with myositis overlapping with other collagen vascular diseases, as well as in 265 controls.
Forty-two patients (35%) were positive for myositis-specific autoantibodies (MSA), including 37 (31%) for anti-aminoacyl-tRNA synthetase (ARS) autoantibodies. Allele carrier frequency of HLA-DRB1*0803 was increased in the patients with IIM p = 0.02, corrected p (pc) NS, 23% vs 14%, odds ratio (OR) = 1.9 (95% confidence interval, CI = 1.1-3.2), with PM p = 0.006, pc NS, 33%, OR 3.1 (95% CI 1.3-7.1), and with anti-ARS autoantibodies 27%, p = 0.04, OR 2.3 (95% CI 1.0-5.1) compared with controls. DRB1*0405 was increased in patients with anti-ARS autoantibodies compared with controls 41% vs 25%, p = 0.04, pc NS, OR 2.1 (95% CI 1.0-4.3). TNF promoter genotype was associated with the presence of interstitial lung disease (ILD). The carriage of a TNF-a haplotype formed by -1031C, -863A, and -857C was increased in the patients with ILD versus those without ILD 33% vs 18%, p = 0.05, pc NS, OR 2.3 (95% CI 0.94-5.5).
HLA-DRB1 alleles were associated with development of IIM and MSA in a Japanese population.
To elucidate the fluid regulation in different menstrual cycle phases during
xercise. Sex hormones affect fluid regulation in different ways. Moreover, the renin angiotensin-aldosterone system is ...activated in the luteal phase in rest. However, there are limited studies on fluid regulation affected by such hormone excretion in the menstrual cycle during exercise, especially during a light walking exercise. A non-invasive method using urine samples to determine menstrual cycle phases was used, and the follicular and luteal phases were successfully confirmed in 10 participants (age, 21 ± 1 years; body mass index, 20.5 ± 2.1 kg/m
). The experimental exercise sessions consisted of 5-min standing and 15-min walking at 2 km/h on 15% slope (approximately 8.3°) on a treadmill. Each participant carried a backpack weighing 5% of her own weight, and performed three sessions of walking exercise. Urine aldosterone excretion was significantly higher in the luteal than in the follicular phase before and after walking (
< 0.05). Urinary excretion of aldosterone was five times higher in the luteal than in the follicular phase before and after walking exercise. Heart rates during walking, after rest, and after recovery were all significantly higher in the luteal than in the follicular phase (p < 0.05). The participants' ratings of perceived exertion during the first and third session of walking in the luteal phase was not higher than that at the follicular phase. The results of our study suggested that increased activity of the renin-angiotensin-aldosterone system in the luteal phase of the menstrual cycle might be further activated during exercise. This may increase the circulatory load, which is reflected as increased heart rate. These results suggested that premenopausal women may better take into account a possibility of an increased circulatory load in the luteal phase even when they perform light exercise.
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