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[Management of hyperuricemia in occupational health: with reference to "guidelines for the management of hyperuricemia and gout"].

In 1996, the need for the clinical guidelines for the management of hyperuricemia and gout was proposed of the consensus conference held at the 29th annual meeting of the Japanese Society of Purine and Pyrimidine Metabolism (president Yuji Matsuzawa). At the consensus conference, the following announcement was made. 1. Because the majority of patients with hyperuricemia are in the condition of multiple risk factor clustering syndrome, hyperuricemia per se should be counted as one of the typical lifestyle related diseases. 2. Medical management should be directed independently for the treatment of gouty arthritis and for control of the serum uric acid level. 3. The serum uric acid level should be taken into account as a possible cardiovascular risk factor. 4. Urine alkalization should be started if there is no symptom indicating hyperuricemia for the prophylaxis of urinary stones and renal dysfunction. 5. All the medical management should be considered under the consensus of the many expert physicians dealing with hyperuricemia and gout. This principal announcement was made by the consensus conference and the simple management recommendation of a 6-7-8 rule was proposed through the consensus of expert physicians. Recently, a guideline committee was organized in the Japanese Society of Gout and Nucleic Acid Metabolism (previous by the Japanese Society of Purine and Pyrimidine Metabolism) and the Guidelines for the Management of Hyperuricemia and Gout were prereleased in February and published in August 2002. In the new guidelines, the above policy was introduced and evidence was collected to give the guidelines contemporary clinical usefulness and value. It will help in the proper management of hyperuricemia in apparently healthy persons in occupational health, having multiple risk factors.

Arteriosclerosis↗

Hyperuricemia, low urine urate excretion and target organ damage in arterial hypertension.

BACKGROUND: Hyperuricemia can be the consequence of an increased urate production, a decreased renal excretion, or both. An increased prevalence of hyperuricemia has been described in essential hypertensive patients partly due to a decreased renal urinary urate excretion (UUE). Hyperuricemia has been shown to be associated with an increased risk of cardiovascular disease in hypertensive patients in some but not in all epidemiological studies in which this relationship has been investigated. OBJECTIVE: To assess the influence of low UUE in the association between serum urate, renal function and hypertension severity. PATIENTS AND METHODS: This cross-sectional study was carried out in a sample of 677 male hypertensive patients, aged 35-60 years, with essential arterial hypertension consecutively attended in a hospital hypertension unit. The presence of hypertension-related organ damage at diagnosis was classified according to classical WHO criteria as grade 1, 2 or 3. Urate underexcretion was defined as 24-h urinary urate below the product serum urate x 100. RESULTS: Mean serum urate levels were 6.4 +/- 1.6 mg/dl in the total sample. Hyperuricemia (serum urate >7 mg/dl) was present in 28.5% of patients and only 17.0% had underexcretory hyperuricemia. This subgroup of patients exhibited the higher rate of hypertension-related target organ damage (TOD). A multivariate analysis, showed that underexcretory hyperuricemia but not hyperuricemia remained an independent predictor of TOD (odds ratio 2.5. 95% CI 1.6-3.89). Serum urate correlated positively with serum creatinine in hyperuricemic patients (r = 0.50, p < 0.001), but not in patients with underexcretory hyperuricemia (r = 0.21, p = 0.18). CONCLUSIONS: Underexcretory hyperuricemia is strongly related to hypertensive organ damage and this relationship does not seem to be mediated by a decreased renal function. This aspect could underline the predictive value of hyperuricemia independently of serum creatinine. UUE could improve the clinical predictive value of hyperuricemia as a cardiovascular risk factor.

Adult↗

Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery.

OBJECTIVE: We investigated changes in serum uric acid across pregnancy in women with gestational hyperuricemia at delivery, with and without preeclampsia, compared with normal pregnant and women with preeclampsia without gestational hyperuricemia. STUDY DESIGN: This was a nested case-control study of 116 controls, 27 women with preeclampsia with predelivery hyperuricemia, 37 women with preeclampsia without predelivery hyperuricemia, and 35 women with gestational hypertension with hyperuricemia at delivery but without proteinuria. Serum uric acid and creatinine was measured across pregnancy. RESULTS: Women with predelivery hyperuricemia, with and without preeclampsia, had increased uric acid concentrations across pregnancy compared with controls, after 25 weeks' gestation compared with women with preeclampsia without predelivery hyperuricemia. Adjusting for differences in glomerular filtration by serum creatinine accounted for part but not all of the increase in serum uric acid among women with preeclampsia and predelivery hyperuricemia. CONCLUSIONS: Among women with hyperuricemia at delivery, elevations in uric acid occur early. Multiple mechanisms may contribute to increased uric acid including changes in renal function.

Adult↗

Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort.

BACKGROUND: Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. METHODS: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. RESULTS: Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. CONCLUSION: Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.

Adult↗

[A cross-sectional study of hyperuricemia in state-employees in Beijing: prevalence and risk factors].

OBJECTIVE: To investigate prevalence of hyperuricemia and its risk factors in Beijing. METHODS: A cross-sectional study was carried out in four groups of state-employees in Beijing, China. Demographic, dietary and clinical data were collected by questionnaires, physical examination, and biochemical assay. Data were analyzed by multivariate logistic regression models. RESULTS: 1217 men and 780 women participated in the study. HDL and LDL were excluded as they were not missing completely at random in missing variable analysis. The serum uric acid level was (331 +/- 74) micromol/L (mean +/- SD) for men and (254 +/- 61) micromol/L (mean +/- SD) for women. It was stable for both sexes before the age of 50, increased in women but tended to decrease in man thereafter. 13.8% of men and 6.0% of women had hyperuricemia, which was defined as serum uric acid >or= 416.4 micromol/L in men and >or= 356.9 micromol/L in women, or taking medication for it. The prevalence of hyperuricemia increased steadily as women aged and surpassed that of men after the age of 70, while it appeared to decrease after 60 in men. Multivariate logistic regression models found that male gender (OR 2.46, 95% CI 1.63 - 3.69), non-Han Chinese ethnicity (OR 2.47, 95% CI 1.02 - 5.98 for Chinese Muslim), renal dysfunction (OR 12.88, 95% CI 4.07 - 40.79 for GFR < 30 ml/min), and diuretics (OR 2.25, 95% CI 1.42 - 3.57) were associated with increased risk of hyperuricemia, whereas retirement (OR 0.21, 95% CI 0.12 - 0.38) was associated with substantially reduced risk of hyperuricemia, after adjusted for overweight/obesity, hypertension and hypertriglyceridemia. Age, menopause, low-dose aspirin were not found to be associated with hyperuricemia independently. Although retirement was associated with less consumption of meat, fat, alcohol (beer, hard liquor, and wine), and more physical exercises, neither of these factors were found to be associated with hyperuricemia independently. CONCLUSIONS: Male gender, non-Han Chinese ethnicity (Muslim), renal dysfunction, diuretics, overweight/obesity, hypertension and hypertriglyceridemia are associated with increased risk of hyperuricemia. Retirement is associated with reduced risk of hyperuricemia.

Adult↗

Hyperuricemia and gout in Taiwan: results from the Nutritional and Health Survey in Taiwan (1993-96).

OBJECTIVE: To evaluate the prevalence of hyperuricemia in Taiwan. METHODS: A multi-stage stratified sampling scheme was used in Nutrition and Health Survey, which was conducted in Taiwan between 1993 and 96. Complete biochemical and questionnaire data for 2754 males and 2953 females aged 4 years and older were included in the analysis. The colorimetric enzymatic method was used to measure plasma uric acid in fasting blood samples. Information on self-reported, physician-diagnosed gout was also obtained. RESULTS: The uric acid values of males were found to reach a peak between the ages of 13 and 18 and decrease slightly after 18. The uric acid values of females were stable before the age of 18, decreasing slightly between 19 and 44 years, and increasing in the mid to older age groups (> or = 45 years). Twenty-six percent of adult males (> or = 19 years) and 22% of older males (> or = 45 years) either had hyperuricemia (serum uric acid > 458.0 microM or 7.7 mg/dl) or were taking medication for it. Seventeen percent of adult females and 23% of older females either had hyperuricemia (serum uric acid > 392.57 microM or 6.6 mg/dl) or were taking medication for it. Both adult males and females in mountainous areas, who were primarily aboriginal, had the highest prevalence of hyperuricemia (> 50%) among the 7 survey areas. Mean body mass index (BMI), alcohol consumption, and prevalence of gout were among the highest in mountainous people compared to all included in the study. Multivariate analysis showed that mountainous area, age and BMI are important factors associated with hyperuricemia in males, whereas mountainous area, Class II townships, and BMI are the factors associated with hyperuricemia in females. CONCLUSIONS: We found a high prevalence of hyperuricemia in Han Chinese in Taiwan despite a lack both of obesity and high alcohol consumption. Mountainous people (mainly aborigines) in Taiwan have an even higher prevalence of hyperuricemia, which cannot be completely explained by obesity and alcohol consumption. Genetic components and other environmental factors may have contributed to this pattern of hyperuricemia.

Adolescent↗

Hemodynamics of hyperuricemia.

Prolonged hyperuricemia is associated with the development of hypertension, renal arteriolosclerosis, glomerulosclerosis, and tubulointerstitial injury. It confers a greater risk than proteinuria for developing chronic renal disease and is associated with the development of hypertension. Mild chronic hyperuricemia without intrarenal crystal deposition was induced in rats by inhibiting uricase with oxonic acid. Hyperuricemic rats developed hypertension, afferent arteriolar thickening, and mild renal interstitial fibrosis. Additionally, hyperuricemia accelerated renal damage and vascular disease in rats undergoing renal ablation. To better understand the role of hyperuricemia in the kidney, micropuncture studies were performed. Hyperuricemia resulted in renal cortical vasoconstriction (single nephron glomerular filtration rate (SNGFR) 35%, P < .05) and glomerular hypertension (P < .05). The possibility that hyperuricemia could modify renal hemodynamic disturbances during progression of renal disease was tested in rats with 5/6 nephrectomy. Hyperuricemia accentuated the renal vascular damage and caused cortical vasoconstriction (SNGFR 40%, P < .05) and persistent glomerular hypertension. In conclusion, hyperuricemia impairs the autoregulatory response of preglomerular vessels, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening results in severe vasoconstriction. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis as well as arterial hypertension.

Animals↗

Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats.

BACKGROUND: Hyperuricemia has been associated with renal disease. Because glomerular hemodynamic alterations critically contribute to initiation and progression of renal disease, we evaluated the effect of mild hyperuricemia in glomerular microcirculatory changes in rats under normal conditions and with renal injury induced by subtotal renal ablation (RK). METHODS: Hyperuricemia was induced in normal and remnant kidney (RK) rats on a normal sodium diet by administration of oxonic acid (OA). To prevent hyperuricemia, allopurinol (AP) was administered concomitantly. Glomerular hemodynamics were evaluated by micropuncture techniques. Systolic blood pressure (SBP), proteinuria, arterial morphology, and serum uric acid were measured. In RK rats, glomerulosclerosis, fibrosis, and inflammatory cell infiltration (CD5+) were also assessed. RESULTS: In normal rats, hyperuricemia resulted in afferent arteriole thickening associated with renal cortical vasoconstriction [single nephron glomerular filtration rate (SNGFR) -35%, P < 0.05) and glomerular hypertension (P < 0.05). Allopurinol treatment prevented structural and functional alterations. In RK rats, hyperuricemia produced more renal vascular damage than control animals coupled with severe cortical vasoconstriction (SNGFR -40%, P < 0.05) and persistent glomerular hypertension. Allopurinol partially prevented cortical vasoconstriction, and fully prevented arteriolopathy and glomerular hypertension associated with significantly less infiltration of CD5+ cells. CONCLUSION: Hyperuricemia induces arteriolopathy of preglomerular vessels, which impairs the autoregulatory response of afferent arterioles, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening produces severe renal hypoperfusion. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis, as well as arterial hypertension. These studies provide a potential mechanism by which hyperuricemia can mediate hypertension and renal disease.

Animals↗

The prevalence of hyperuricemia in a population of the coastal city of Qingdao, China.

OBJECTIVE: Hyperuricemia and gout have shown an increase worldwide. Data are lacking for the prevalence of hyperuricemia and gout and their correlates in China. We studied the occurrence of these conditions in Chinese adults in the city of Qingdao. METHODS: A population-based cross-sectional survey for hyperuricemia and gout was performed among 2438 adults (1535 women, 903 men; aged 20-74 yrs) in 2002. Fasting serum uric acid (UA) and lipid profiles were determined, as well as height, weight, and blood pressure. Hyperuricemia was defined as serum UA levels >or= 420 micromol/l in men and >or= 360 micromol/l in women. Diagnosis of gout was self-reported. Complete biochemical and questionnaire data were available for analysis from 1303 women and 720 men. RESULTS: The age-standardized prevalence was 25.3% for hyperuricemia and 0.36% for gout in adults aged 20 to 74 years. Hyperuricemia was more prevalent in men than in women (32.1% vs 21.8%; p < 0.001). Age-adjusted mean serum UA level was 389.3 micromol/l in men and 315.7 micromol/l in women. Serum UA increased with age in women only (p for trend < 0.001). Body mass index and serum triglycerides had the strongest associations with serum UA in both genders, followed by alcohol drinking and diastolic blood pressure in men, and systolic blood pressure and total cholesterol in women. CONCLUSION: The prevalence of hyperuricemia in the urban adult population in Qingdao city is high, while the frequency of gout is lower. Obesity, hypertension, and dyslipidemia are the major factors associated with hyperuricemia in this study.

Adult↗

Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen.

OBJECTIVE: This is a population survey conducted in 1991-92 among residents aged > or =30 years in Kin-Hu, Kinmen, with a 77.7% response rate to study the prevalence of hyperuricemia and hyperuricemia associated gout. A stratified analysis based on sex and age was used to assess the interaction and analyze the associated risk factors for hyperuricemia and gout. METHODS: Hyperuricemia was defined as uric acid > or =7.0 mg/dl for men and > or =6.0 mg/dl for women. Gout was clinically diagnosed by a senior rheumatologist based on patient's history and examination according to the clinical criteria of Wallace. Basic demographic and lifestyle variables as well as biochemical data were collected. RESULTS: The prevalence of hyperuricemia was 25.8% (391/1515) in men and 15.0% (250/1670) in women. The prevalence of gout among hyperuricemic subjects was 11.5% for men and 3% for women. According to age spectrum, the risk factor for hyperuricemia was hyperlipidemia in young adults (30-39 yrs); lifestyle and some clinical syndromes played a significant role in middle aged persons (40-59 yrs). The different risk factors between the sexes in middle age were alcohol consumption effect in men and menopause effect in women. Impaired renal function and use of diuretics became the important factors in the elderly (> or =60 yrs). The risk factors for gout among either the general population or subjects with hyperuricemia were concentration of serum uric acid, alcohol consumption, and central obesity. CONCLUSION: Risk factors for hyperuricemia tended to be different with respect to sex and age. Alcohol consumption and central obesity were independent predictors of gout among hyperuricemic subjects irrespective of uric acid level.

Adult↗

[Hyperuricemia in hypertension].

Hyperuricemia is one of the common complications in hypertension. The presence of hyperuricemia is closely correlated with the initiation of hypertension. In addition, the hypertension is known to increase the rate of hyperuricemia. Recently, it has been recognized that the hyperuricemia is one of the risk factors for cardiovascular events in hypertension. Therefore, the control of hyperuricemia might be critical for treatment of hypertension. Although the diuretics are important for the treatment of chronic heart failure and hypertension, it is reported to induce the hyperuricemia. Therefore, the careful and combination therapy for diuretics might be necessary to prevent the treatment-induced hyperuricemia. In the treatment of hypertension, especially with hyperuricemia, it might be important to select the drug, which does not influence or reduce the concentration of uric acid.

Antihypertensive Agents↗

Epidemiology of hyperuricemia in the elderly.

BACKGROUND: Our study used data collected in Chung-Hsing Village to evaluate the relationship between hyperuricemia and the cardiovascular risk factors and the socio-demographic factors in the elderly in May 1998. METHODS: All individuals aged 65 and over were studied. A total of 1093 subjects, out of 1774 registered residents, were contacted by face-to-face interview. The response rate was 61.6 percent. However only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. To study the significant correlates of hyperuricemia, t- test, two-way ANOVA, chi-square test and multivariate logistic regression were used. RESULTS: Our results showed that 66 percent were men and 34 percent were women. The mean age was 73.1+/-5.3 years. The proportions of hyperuricemia were 57.3 percent in men and 40.9 percent in women (p < .01). In chi-square test, hypercholesterolemia, hypertriglyceridemia, renal function impairment, retirement status and marital status were related to hyperuricemia. After controlling the other covariates, the multivariate logistic regression analysis showed that the significant related factors of hyperuricemia were hypercholesterolemia, hypertriglyceridemia, and renal function impairment. CONCLUSIONS: Hyperuricemia is often found in the elderly. Hyperuricemia is more common in elderly men than in elderly women. A large-scale investigation will be suggested in the future to address causal-effect issues between hyperuricemia and hypercholesterolemia, hypertriglyceridemia, or renalfunction impairment.

Aged↗