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PubMed1995

Clinical and biochemical presentation of gouty diathesis: comparison of uric acid versus pure calcium stone formation.

PURPOSE: We compared gouty diathesis with uric acid versus calcium stones. MATERIALS AND METHODS: We retrospectively reviewed clinical and laboratory data from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones) and 99 normal subjects. RESULTS: Of the gouty diathesis patients gouty arthritis was present in 21% of those with uric acid and 12% of those with calcium stones. Hyperuricemia developed in 43% of those with uric acid and 27% of those with calcium stones, and 2% of controls. Urinary pH was independent of the net gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH and citrate increased after potassium citrate treatment. CONCLUSIONS: The characteristic features of primary gout were present in both gouty diathesis groups and both are responsive to treatment.

Adult↗
PubMed1993

[Evaluation of uric acid transport in nephrons of patients with calcium nephrolithiasis and hyperuricosuria].

Renal excretion of uric acid was studied in 48 patients with recurrent calcium nephrolithiasis. Hyperuricosuria was found in 16 patients (33%) and among them 10 patients had increased values of urate clearance and fractional excretion. The tubular transport of urate was evaluated by means of pharmacological tests with pyrazinamide (PZA) and benzbromarone (BB) in these 11 patients with hyperuricosuria of renal origin. PZA suppression test was normal in 10 patients while in one case uric acid excretion was not suppressed sufficiently by PZA. Maximal uricorusirc response to BB was increased in two patients, normal in one patient and impaired in eight patients. PZA and BB tests revealed isolated defect of uric acid postsecretory reabsorption in seven patients, impaired reabsorption at both pre- and postsecretory site in one case and enhanced tubular secretion of uric acid in two patients. This study indicates that different defects of uric acid transport in nephron are the frequent cause of hyperuricosuria in patients with recurrent calcium nephrolithiasis.

Absorption↗
PubMed1998

Uric acid in the aqueous humor and tears of retinoblastoma patients.

PURPOSE: Malignancy can be associated with high levels of catabolic products. We performed a two-part study. Part 1 measured levels of uric acid and xanthine in the aqueous humor of eyes with malignant and nonmalignant diagnoses. Part 2 measured the levels of uric acid in tears of retinoblastoma patients. If compounds in high concentrations inside the eye could be detected outside the eye, via diffusion, in high concentrations in the tears, then a tear screening test for retinoblastoma could be developed. METHODS: High-performance liquid chromatography measured levels of uric acid and xanthine in aqueous humor samples of patients with retinoblastoma, melanoma, Coats' disease, adult cataract, and congenital cataract. Tear sampling was performed on patients with retinoblastoma and on normal eyes, and samples were assayed for uric acid. RESULTS: Part 1--Uric acid was elevated in the aqueous humor of eyes with retinoblastoma, melanoma, and Coats' disease compared with eyes with cataracts. Xanthine was elevated in retinoblastoma and Coats' disease and was lower in adult and congenital cataracts and melanoma. Part 2-No significant difference was found in the concentrations of uric acid in the tears of patients with retinoblastoma and those of normal patients. CONCLUSIONS: High levels of uric acid and xanthine present in the aqueous humor of patients with malignancy are consistent with the destructive nature of these conditions. Although uric acid was not elevated in the tears of retinoblastoma patients, continued investigation into substances that might be measurably different in the tears may yield a useful screening test in the future.

Adult↗
PubMed2005

Serum uric acid concentration as a risk factor for cardiovascular mortality: a longterm cohort study of atomic bomb survivors.

OBJECTIVE: To elucidate the association of serum uric acid concentration with cardiovascular mortality risk. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed2006

The association between serum uric acid level and long-term incidence of hypertension: Population-based cohort study.

Increasing experimental evidence, including recently developed animal models support a causal role for uric acid in the development of hypertension. However, it is not clear whether serum uric acid levels are independently associated with the long-term incidence of hypertension. We examined the association between serum uric acid levels and 10-year incidence of hypertension in a population-based cohort study based in Beaver Dam city and township, Wisconsin, US. We studied 2520 hypertension-free individuals (56.3% women, age: 43-84 years, 98% Caucasian) at the baseline examination (1988-1990). The main outcome of interest was hypertension (systolic blood pressure (BP) of 140 mm Hg or higher, diastolic BP 90 mm Hg or higher, or combination of self-reported high BP diagnosis and use of antihypertensive medications) incidence over 10 years among baseline normotensive individuals. Nine hundred and fifty-six individuals developed hypertension over a 10-year follow-up period. The relative risk (RR) (95% confidence intervals (CI)) of incident hypertension increased in a dose-dependent manner (P-trend < 0.05 in all models) with increasing uric acid quartiles. Multivariable RR (95% CI) comparing the highest quartile of serum uric acid (> or =390 micromol/l) to the lowest quartile (< or =260 micromol/l) was 1.65 (1.41-1.93). This association persisted in subgroup analyses by categories of smoking, alcohol intake, body mass index, baseline blood pressure and estimated glomerular filtration rate (GFR). In conclusion, increasing quartiles of serum uric acid was associated with 10-year incidence of hypertension independent of smoking, alcohol intake and baseline kidney function suggesting an independent positive association between serum uric acid levels and hypertension development among community-dwelling older adults.

Adult↗
PubMed2005

Serum uric acid concentrations in type 2 diabetes: its significant relationship to serum 1,5-anhydroglucitol concentrations.

OBJECTIVE: Serum uric acid concentrations in diabetics are well known to be significantly lower than those in non-diabetic subjects, due to increased its urinary clearance. Serum 1,5-anhydroglucitol concentrations are also specifically decreased in diabetics through the increased urinary excretion. To gain an insight into the idea that a common mechanism might be possible to work in reducing these serum substances, this study was conducted. METHODS: A total of 121 type 2 diabetic patients, 76 males and 45 females, were studied. Multiple regression analysis was performed to determine the independent association between potential predictor variables (mean blood pressure, body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, serum fructosamine, serum 1,5-anhydroglucitol, serum creatinine, serum total cholesterol, and serum triglycerides) and serum uric acid concentrations as the dependent variable. RESULTS: In the male subjects, serum 1,5-anhydroglucitol, serum creatinine and body mass index were the variables independently related to serum uric acid concentrations. In the female subjects, serum 1,5-anhydroglucitol and serum creatinine were the variables independently related to serum uric acid concentrations. CONCLUSION: Considering the glucosuria-related urinary excretion of 1,5-anhydroglucitol, a close positive association between serum uric acid and 1,5-anhydroglucitol concentrations strongly supports the idea that the reduction in serum uric acid concentrations is mediated by urinary glucose excretion in diabetics.

Adult↗
PubMed1997

Catalytic oxidation of uric acid at the polyglycine chemically modified electrode and its trace determination.

Cyclic voltammetry was undertaken to investigate the electrochemical behavior of uric acid at a polyglycine modified electrode. The modified electrode shows catalytic ability for the oxidation of uric acid, reducing the overpotential by 250 mV in pH 7.0 phosphate buffer solution. The enhanced voltammetric response can be used to determine uric acid. The linear range is between 5.0 x 10(-8) and 4.5 x 10(-6) M with a detection limit as low as 5.0 x 10(-9) M. The relative standard deviation is 1.4% (8 runs) at a concentration of 50 microM uric acid. The catalytic effect of the modified electrode resulted in the voltammetric resolution of the overlapping of uric acid and ascorbic acid. This allows the simultaneous detection of uric acid and ascorbic acid in the same sample.

Catalysis↗
PubMed2005

Clinical evidence for the influence of uric acid on hypertension, cardiovascular disease, and kidney disease: a statistical modeling perspective.

This article critically evaluates the clinical evidence regarding the influence of uric acid on hypertension, cardiovascular disease, and kidney disease. Data on these relationships are largely observational and exceedingly complex. The complexity is owing to indirect and direct relations, and bidirectional influences, simultaneously operating on multiple outcomes. Limitations of previous analyses include inadequate statistical methods using only bivariate correlations or poorly specified multiple regression models. As a result, great controversy developed as to whether uric acid is an independent predictor of important outcomes. An example of such analytic limitations is including hypertension as an independent variable, together with uric acid, in a multivariate model for predicting cardiovascular disease. Hypertension may predict significant variance in cardiovascular disease, but the contribution of uric acid may not be recognized if uric acid exerts its influence indirectly through hypertension. Path analysis, which can model direct and indirect influences on outcomes simultaneously, would address this substantive question. Studies of uric acid in relation to hypertension, cardiovascular disease, and kidney disease using a path-analytic approach would help specify such conditions as well as optimize design of clinical trials to determine if decreasing uric acid levels improves outcomes.

Cardiovascular Diseases↗
PubMed1998

Analysis of the relationship between fasting serum uric acid and the insulin sensitivity index in a population-based sample of 380 young healthy Caucasians.

AIM: To determine whether fasting serum uric acid is associated with the insulin sensitivity index or with other anthropometric, metabolic or environmental features of the insulin resistance syndrome in a population-based sample of young healthy Caucasians. METHODS: The protocol included 380 unrelated Caucasian subjects (age 18-32 years) who had their insulin sensitivity index and glucose effectiveness measured during a combined intravenous glucose (0.3 g/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. A number of anthropometric and biochemical tests, including the level of fasting serum uric acid, were carried out. RESULTS: In univariate analyses the concentration of fasting serum uric acid was negatively correlated to the insulin sensitivity index in both men (r2 = -0.25, P = 0.001) and women (r2 = -0.25, P < 0.001). In multivariate analysis controlling for age, gender, body mass index, waist to hip ratio, maximal aerobic capacity, fasting serum triglyceride and creatinine, daily intake of alcohol, smoking, use of oral contraceptives, and disposition for non-insulin dependent diabetes mellitus, the insulin sensitivity index was not significantly associated with fasting serum uric acid. However, 51% of the variation in the fasting serum uric acid level could be explained, and fasting serum triglyceride was the most important determinant of fasting serum uric acid. CONCLUSION: The major determinant of the fasting serum uric acid level in young healthy Caucasians is the fasting concentration of serum triglyceride, which has been shown to be a biochemical feature of the insulin resistance syndrome. Thus, hyperuricaemia appears to be an indirect part of the insulin resistance syndrome through its association with fasting hypertriglyceridaemia.

Adult↗
PubMed2000

The C677T mutation in the methylene tetrahydrofolate reductase gene increases serum uric acid in elderly men.

A common mutation, C677T, in the methylene tetrahydrofolate reductase gene (MTHFR) reduces the activity of MTHFR and increases total homocysteine levels in plasma. Increased homocysteine levels are reportedly associated with high serum uric acid levels. The relationship between the MTHFR mutation and uric acid metabolism remains unclear, however. To investigate whether the C677T MTHFR mutation is a risk factor for hyperuricemia, we performed MTHFR genotyping and clinical laboratory determinations, including serum uric acid, in 271 elderly Japanese men (age range, 40-79 years; mean, 52.6 years). The mean uric acid levels for the C/C, C/T, and T/T genotypes were 5.67, 6.00, and 6.39 mg/dl, respectively (P = 0.012). The T/T genotype was more frequent in subjects with high uric acid levels than in those with low uric acid levels (P = 0.038). These findings suggest that the C677T MTHFR mutation contributed to higher uric acid levels in subjects enrolled in this study. In conclusion, the mutation of the MTHFR gene may be a risk factor for hyperuricemia in elderly men.

Adult↗
PubMed1981

Gut bacteria recycle uric acid nitrogen in termites: A strategy for nutrient conservation.

Reticulitermes flavipes termites synthesize uric acid via purine-nucleoside phosphorylase (purine-nucleoside: orthophosphate ribosyltransferase, EC 2.4.2.1) and xanthine dehydrogenase (xanthine:NAD(+) oxidoreductase, EC 1.2.1.37), but their tissues lack uricase (urate:oxygen oxidoreductase, EC 1.7.3.3) or any other enzyme that degrades uric acid. Nevertheless, uricolysis occurs in termites, but as an anaerobic process mediated by hindgut bacteria. (14)C-Tracer experiments showed that termites transport uric acid from the site of synthesis and storage (fat body tissue) to the site of degradation (hindgut microbiota) via Malpighian tubules. Moveover, [1,3-(15)N]uric acid dissimilated by gut bacteria in vivo leads to assimilation of (15)N into termite tissues. NH(3), a product of uricolysis, is a potential N source for termites, either directly via glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] activity of fat body tissue or indirectly through microbe assimilation. Symbiotic recycling of uric acid N appears to be important to N conservation in these oligonitrotrophic insects.

Journal Article↗
PubMed2006

An amperometric biosensor for uric acid determination prepared from uricase immobilized in polypyrrole film.

In order to prepare a biosensor for the determination of uric acid, electropolymerization of pyrrole on Pt surface was carried out with an electrochemical cell containing pyrrole, ferrocene (as a electron mediator) and tetrabutylammonium tetrafluoroborat in acetonitrile by cyclic voltammetry between 0.0 and 1.0 V (vs. Ag/AgCl) at a scan rate of 50 mV/s upon Pt electrode. Uricase was immobilized by a glutaraldehyde/gelatine croslinking procedure on to polypyrrole film after the electropolymerization processes. The response of the biosensor against uric acid was measured after 330 seconds following the application of a constant potential of +0.7 V (vs. Ag/AgCl). The resulting biosensor exhibits excellent electrocatalysis for the uric acid. The amperometric determination is based on the electrochemical detection of H2O2, which is generated in enzymatic reaction of uric acid. The sensor responds to uric acid with a detection limit of 5.0 x 10(-7) M. The sensor remains relatively stable for 5 weeks. Interference effect were investigated on the amperometric response of the biosensor. Determination of uric acid was carried out in the biological fluids by biosensor.

Acetaminophen↗
PubMed2006

Evaluation of a kinetic uricase method for serum uric acid assay by predicting background absorbance of uricase reaction solution with an integrated method.

A patented kinetic uricase method was evaluated for serum uric acid assay. Initial absorbance of the reaction mixture before uricase action (A(0)) was obtained by correcting the absorbance at 293 nm measured before the addition of uricase solution, and background absorbance (A(b)) was predicted by an integrated method. Uric acid concentration in reaction solution was calculated from A, the difference between A(0) and A(b), using the absorptivity preset for uric acid. This kinetic uricase method exhibited CV<4.3% and recovery of 100%. Lipids, bilirubin, hemoglobin, ascorbic acid, reduced glutathione and xanthine <0.32 mmol/L in serum had no significant effects. A linearly responded to 1.2 to 37.5 micromol/L uric acid in reaction solution containing 15 microl serum. The slope of linear response was consistent with the absorptivity preset for uric acid while the intercept was consistent with that for serum alone. Uric acid concentrations in clinic sera by different uricase methods positively correlated to each other. By Bland-Altman analysis, this kinetic uricase method accorded with that by quantifying the total change of UV absorbance on the completion of uricase reaction. These results demonstrated that this kinetic uricase method is reliable for serum uric acid assay with enhanced resistance to both xanthine and other common errors, wider range of linear response and much lower cost.

Humans↗
PubMed1981

Effect of repeated doses of hydroflumethiazide on renal excretion of electrolytes and uric acid in healthy subjects.

Urinary excretion of electrolytes and uric acid was investigated in six healthy subjects during repeated oral administration of 100 mg hydroflumethiazide (HFT) daily for seven days, and related to urinary thiazide excretion. Mean 24 hr-urinary excretion of sodium and chloride increased 100% (P less than 0.02) after the first HFT-dose, whereas 24 hr-excretion values were at control level after the fourth and seventh doses. Mean 24 hr-urinary excretion of potassium was increased by 31% after the first HFT-dose (P less than 0.05) and by 47% after the fourth dose (P less than 0.05). After HFT was discontinued, mean urinary excretion rates of sodium and chloride dropped to 30% and that of potassium to 70% of control. In the state of fluid deficiency and elevated aldosterone concentration, there was a significant positive correlation between log excretion rate of HFT and excretion rate of sodium (r=0.68, P less than 0.002) calculated from excretion data 0-67, 6-12, and 12-14 hrs after the seventh dose. After the first dose of HFT, sodium excretion was also significantly correlated to log excretion rate of HFT (r=0.86, P less than 0.001) but was probably influenced by other factors as well. Mean serum concentration of uric acid increased significantly, but mean 24 hr-urinary excretion of uric acid was constant during HFT-treatment.

Adult↗
PubMed1990

Uric acid levels in southern Germany in 1989. A comparison with studies from 1962, 1971, and 1984.

Since 1962 our group has performed four studies on uric acid values in blood donors in southern Germany (Bavaria). Uric acid levels in men have increased over the years, from 4.86 mg/dl in 1962 to 6.00 mg/dl in 1971, 5.60 mg/dl in 1984, and 5.90 mg/dl in 1989. Levels in women have increased slightly, from 4.05 mg/dl in 1962 to 4.35 mg/dl in 1971, 4.10 mg/dl in 1984, and 4.16 mg/dl in 1989. Women aged 51 to 60 years had significantly higher uric acid levels than those in the fourth decade. In women treated with oral contraceptives uric acid levels were significantly lower than in other women of the same age. Hypouricemia (uric acid levels less than or equal to 2.0 mg/dl) was observed in three women, none of whom had a history of medication. Hyperuricemia exists when uric acid levels are greater than or equal to 6.5 mg/dl. In 1989 2.6% of the female blood donors and 28.6% of the males were hyperuricemic, with an increased risk of gout, nephrolithiasis, and nephropathy.

Adult↗
PubMed1984

[Effect of sex steroids in vivo and in vitro on the binding of uric acid to plasma proteins].

Modifications on the binding of uric acid to human plasma proteins have been studied in regularly menstruating females aged 25-30 years with a normal cycle, in comparison with a group of healthy age-matched males and with a group of post-menopausal females. The binding of uric acid to plasma proteins was estimated using micropartition system Amicon. The results obtained demonstrate a significant increase of uric acid binding during ovulatory and mid-luteal phase of menstrual cycle. No modifications are shown in post-menopausal females and in healthy males. No modifications have been shown with the same experiments performed in vitro.

Adult↗
PubMed1996

Effects of various methods of preservation on the stability of uric acid in frozen canine urine.

OBJECTIVE: To evaluate the effects of dilution and alkalinization, separately and together, on the stability of uric acid in canine urine stored at -20 C. DESIGN: Prospective-controlled study. ANIMALS: 5 dogs with confirmed ammonium urate uroliths, 6 Beagles, and 6 mixed-breed dogs. PROCEDURE: Dogs were fed a 31.4% protein (dry weight), meat-based diet for 21 days, and urine samples were collected on day 22. Urine samples were preserved, using combinations of dilution and alkalinization, and divided into 1-ml aliquots for storage at -20 C for 1 to 12 weeks. Urine uric acid concentrations were measured, using high-performance liquid chromatography, on day of collection (baseline), and after 1, 2, 4, 8, and 12 weeks. RESULTS: Alkalinization did not have a significant effect on reproducibility of measurements of uric acid concentrations in urine; however, dilution did have a significant effect. Compared with baseline, uric acid concentrations in urine samples collected from dogs with ammonium urate uroliths and Beagles and diluted 1:10 or 1:20 with deionized water were not different after storage for 1 to 12 weeks. Uric acid concentrations in urine samples collected from mixed-breed dogs did not differ from baseline values during the 12-week storage period whether samples were undiluted or were diluted 1:10 or 1:20 with deionized water. CONCLUSIONS: Measurements of uric acid concentration are most reproducible in canine urine samples stored at -20 C for 1 to 12 weeks when samples are diluted 1:20 with deionized water. CLINICAL RELEVANCE: To ensure reproducibility of measurements of uric acid concentration in urine samples collected from dogs affected with urate uroliths, urine should be diluted 1:20 with deionized water. Alkalinization is not necessary, and is not recommended because of the additional step in processing and its potential to interfere with measurement of other urinary analytes.

Animals↗
PubMed1999

Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension.

OBJECTIVE: The influence of angiotensin II AT-1 receptor antagonists on uric acid metabolism, and the potential differences among them with regard to this effect, remains to be precisely established. This study was designed to compare the effects of losartan and eprosartan on uric acid metabolism in patients with mild to moderate essential hypertension. DESIGN: Randomized, double-blind, parallel-group study in hypertensive patients. SETTING: Outpatient clinic. PATIENTS: Following a 2- to 3-week single-blind placebo run-in period, 60 patients with sitting diastolic blood pressure > or = 95 and < or = 114 mmHg were randomized. Fifty-eight patients completed the study. INTERVENTIONS: Patients were randomized to receive losartan 50 mg or eprosartan 600 mg once daily for 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the change in the ratio of urinary uric acid/creatinine in the period 0-4 h of a 24 h urine collection after 4 weeks of treatment. Secondary endpoints included 24 h urinary uric acid excretion, as well as serum urate and anti-hypertensive efficacy. RESULTS: Mean urinary uric acid/creatinine changes from baseline were 0.14 (day 1) and 0.11 (week 4) for losartan and -0.04 for eprosartan (at both day 1 and week 4; P < 0.01 between groups at both time-points). The mean increase in 24 h urinary uric acid excretion with losartan was 0.7 mmol/24 h (25% increase from baseline) at both day 1 and week 4. No significant difference was observed in the change of serum urate levels versus baseline between both treatment groups after 4 weeks (- 23.4 and - 19.5 micromol/l for losartan and eprosartan, respectively). Patients with hyperuricaemia in both treatment groups showed similar modifications of uric acid metabolism compared with non-hyperuricaemic subjects. Blood pressure control (sitting diastolic blood pressure < 90 mmHg or < 100 mmHg with a decrease of at least 10 mmHg from baseline) was achieved in 22 patients (73%) with eprosartan and in 16 (53%) with losartan. CONCLUSIONS: Losartan increased uric acid excretion in hypertensive patients, whilst eprosartan did not Neither AT-1 receptor antagonist substantially modified serum urate concentrations.

Acrylates↗