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PubMed1978

Specific method for determining uric acid in serum using high-performance liquid chromatography and gas chromatography-mass spectropmetry.

A method using a combination of high-performance liquid chromatography and stable-isotope dilution-mass spectrometry is described for the specific quantitation of uric acid in serum. The procedure involves addition of a known amount of [1,3,9-15n]uric acid, as intenral standard, to the serum sample followed by equilibration with the endogenous analyte. After separation from serum proteins, cationic and neutral compounds by anion-exchange chromatography, the purified uric acid is converted into its tetraethyl derivatives. High-performance liquid chromatography is used to isolate the three major isomeric derivatives for measurement of the isotope ratio m/e 280 to m/e 283. This ratio gives the relative abundances of the molecular ions of natural and of labelled tetraethyluric acid, and from it the amount of uric acid in the original serum specimen is determined. Effective separation of tetraethyluric acid isomers can be achieved by adsorption or reversed-phase high-performance liquid chromatography using n-heptane-isopropanol (80:1, v/v) and methanol-water (3:2, v/v), respectively, as solvent systems.

Adsorption↗
PubMedDate not supplied

In vivo and in vitro degradation of urea and uric acid by encapsulated genetically modified microorganisms.

This study was undertaken to characterize the capacity of a combination of genetically modified bacteria to lower elevated levels of urea and uric acid and thus to serve as a potential adjunct to maintenance dialysis in patients with chronic renal failure. Two strains of genetically modified bacteria expressing enzymes, urease to degrade urea and uricase to degrade uric acid, were identified, combined, and dispersed in 600-microm alginate microcapsules suitable for oral administration. In 24 h in vitro experiments, 5 mL of these capsules completely cleared 95% of the urea and >99% of the uric acid from 100 mL of a challenge solution formulated to the concentration of these solutes in a presenting hemodialysis patient. The process of urea degradation was found to be intracellular and each bacterial strain was specific for its substrate. Solute degradation in vivo was evaluated with a chemically induced model of acute renal failure, using Sprague-Dawley rats. Orally administered capsules were found to remain in the gastrointestinal tract for at least 6 h. The severity of azotemia and hyperuricaemia after chemical induction of acute renal failure was reduced by 64 and 31%, respectively, on administration of the capsules. Reduction of urea concentration (but not uric acid concentration) in vivo required coadministration of an ion-exchange resin to adsorb ammonia. Oral delivery of a combination of genetically modified microorganisms should be further explored in chronic renal failure models as a useful adjunct to dialysis or to immunosorption for the treatment of uremia.

Acute Kidney Injury↗
PubMed1983

Renal handling of uric acid in normal subjects by means of the pyrazinamide and probenecid tests.

Pyrazinamide and probenecid tests were used to study the renal mechanisms for urate excretion in 10 normal subjects in the state of low serum uric acid levels (below 3.5 mg/dl), normal serum urate concentrations (between 3.6 and 6.4 mg/dl) and high serum uric acid levels (above 6.5 mg/dl). Presecretory reabsorption of urate was above 99% in all three conditions of uricemia, indicating that filtered urate is nearly completely reabsorbed in the proximal tubule regardless of serum uric acid concentrations. Urate secretion was significantly higher and postsecretory reabsorption was significantly lower when serum uric acid was raised than when serum urate levels were normal or low. The findings indicate that both urate secretion and postsecretory reabsorption play a role in urate homeostasis in states of hyperuricemia.

Adult↗
PubMed1997

Sweat urea, uric acid and creatinine concentrations in uraemic patients.

Concentrations of creatinine, uric acid and urea were measured in the blood and urine of female patients at the final stage of renal disease and on a regular lifelong programme of haemodialysis. The samples were collected in winter-time and in summertime. The same analytes were also measured in sweat fluid at the time of collecting summer samples. The results showed insignificant physiological seasonal changes for creatinine and uric acid and that the concentration of these compounds in the sweat fluid was low. Urea concentration in the sweat fluid was found to be present at a much higher concentration than the serum level (reaching in some cases 50 times the serum level). The possibility of using thermal induction as an alternative to haemodialysis is suggested. The presence of urea in the sweat fluid at such a high level suggests a selective transport mechanism across the eccrine sweat gland to clear the blood of a high urea level.

Adult↗
PubMed1991

Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts.

Uric acid stone formation ordinarily is prevented by increases in the urinary pH after meals. This postprandial alkaline tide is lost in patients who make such calculi. Single dose, alternate day administration of an alkaline potassium salt will increase urinary pH and simulate this normal physiological mechanism. An important part of the regimen is patient self-monitoring to verify that the urinary pH increases to greater than 6.8, 1 1/2 to 2 hours after the medication is taken. In contrast to multiple dose daily regimens, this mode of base administration is tolerated better and easier to follow. In 17 patients, 7 with the recurrent gravel/colic syndrome and 10 with prior stones, this regimen abolished calculus formation during an average followup of 2 1/2 years. However, further studies are needed before this regimen can be recommended as standard therapy for uric acid stone prophylaxis.

Adult↗
PubMed2006

Uric acid: its relationship to renal hemodynamics and the renal renin-angiotensin system.

Reports relating hyperuricemia and hypertension have been filed for many decades. Nevertheless, controversy remains concerning serum uric acid concentration as an independent risk factor underlying coronary heart disease (CHD) and essential hypertension or as an indirect marker of renovascular involvement. Earlier studies in normotensive subjects and hypertensive patients demonstrated that serum uric acid concentration was closely related to intrarenal hemodynamic alterations, suggesting that it is an excellent marker of vascular involvement. Our data from clinical studies and in an animal model of severe hypertensive nephrosclerosis have strengthened this concept. Conversely, other reports have suggested that uric acid may be a pathogenetic factor. Supporting arguments for this theory maintain that experimental hyperuricemia induces hypertension and renal damage. Epidemiologically, hyperuricemia is associated with hypertension, CHD, renal disease, toxemia of pregnancy, and other outcomes, although mechanisms remain unclear. Additionally, there are no available data on the effects of lowering uric acid on pressure control and organ protection.

Humans↗
PubMed1985

[A clinical study of urolithiasis in Shizuoka City Hospital--stone analysis and 24-hour urine calcium and uric acid levels].

Stone analysis was performed for 216 urinary calculi which were obtained from 205 patients in our hospital from January, 1980 to June, 1984. The results revealed 161 calcium stones, 21 uric acid stones, 19 struvite stones, 2 cystine stones and 13 others. Sixty one of the 205 patients (male 44, female 17) and 19 controls (male 11, female 8) were investigated for 24-hour urine calcium and uric acid. Forty seven of the patients had calcium stones, 7 of the patients had uric acid stones and 7 of the patients had struvite stones. The mean 24-hour urine calcium level was 146.8 +/- 76.5 mg/day for the male controls and 139.1 +/- 69.9 mg/day for the female controls. The mean 24-hour urine uric acid level was 528.1 +/- 132.6 mg/day for the male controls and 362.0 +/- 135.2 mg/day for the female controls. The mean 24-hour urine calcium level for the male calcium-stone group was 214.6 +/- 96.8 mg/day, and it was significantly higher than that for the male controls (p less than 0.05). The 24-hour urine analysis revealed abnormalities in 17 urolithiasis patients (27.9%) including hypercalciuria in 11 patients (18.0%) and hyperuricosuria in 9 patients (14.1%).

Adolescent↗
PubMed1987

Elevated serum uric acid--a facet of hyperinsulinaemia.

In a representative sample of the adult Jewish population in Israel (n = 1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r = 0.316, p less than 0.001) and females (r = 0.236, p less than 0.001). This association remained statistically significant in both sexes (p less than 0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

Adult↗
PubMedDate not supplied

Comparison of the effects of halofenate (MK-185) and clofibrate on plasma lipid and uric acid concentration in hyperlipoproteinemic patients.

The plasma lipid and serum uric acid lowering effect of halofenate (MK-185, 1 g/day) was compared with the action of clofibrate (2 g/day) in a double-blind 1-yr study in 23 patients with Type 2, 3, 4, and 5 hyperlipoproteinemia. It could be demonstrated that clofibrate decreased the plasma cholesterol concentration significantly to 75% and the triglyceride concentration to 49% of the placebo period level. Halofenate produced no consistent effect on plasma cholesterol but ther was an average reduction of the plasma triglyceride concentration to 84%, which was, however, not significant. If only the Type 4 patients were taken into account, a mean significant decrease to 47% of the triglyceride concentration was observed during the second 24-week period of treatment. In contrast, halofenate lowered the serum uric acid concentration significatnly to 77% of the placebo period level, whereas the decreasing action of clofibrate was weaker (88%) and of lesser significance.

Adult↗
PubMed2000

Method for the synthesis of uric acid derivatives.

A general procedure to obtain tetra-substituted uric acid by stepwise N-alkylation is described. 2,6-Dichloropurine (1) was condensed with 1-propanol by Mitsunobu reaction to give 9-propyl congener (2). Treatment of 2 with ammonia gave adenine derivative (4a), which was converted to the 8-oxoadenine (5b) in 3 steps. Methylation of 5b proceeded site-specifically to give 6-amino-2-chloro-7,8-dihydro-7-methyl-9-propylpurin-8-one (6) as a sole product. Compound 6 was successively treated with NaNO2 and iodomethane to give 2-chloro-1,6,7,8-tetrahydro-1,7-dimethyl-9-propylpurin-6,8-dione (9) accompanied by the O6-methyl product (8) in 75% and 6.9%, respectively. After nucleophilic substitution of 9 with NaOAc, the product (11) was reacted with iodomethane to give the uric acid (12) and the 2-methoxy product (13) in 46% and 15.5%, respectively. However, the reaction of 11 with the benzylating agents gave only O-benzyl products (14a,b).

1-Propanol↗
PubMed1979

[The prognostic value of raised uric acid in the blood in arterial hypertension in pregnancy. 58 cases (author's transl)].

The authors have carried out research in 58 cases to see whether the findings of high uric acid levels in the blood are of prognostic value in all cases of arterial hypertension in pregnancy whatever the aetiology. The material studied consisted of 30 true cases of toxaemia of pregnancy, 13 cases of recurrent toxaemia and 15 cases of the vasculo-renal syndrome on top of the pre-existing pathological condition. In 37 cases where the blood uric acid level was lower than 300 micromoles there were only 4 minor complications. Serious complications were found in 6 cases in which the patients had a blood uric acid level highthan 480 micromoles. This study confirms the prognostic value of blood uric acid levels. The estimation of these levels, however, seems to be of less value in making a differential diagnosis between the various kinds of toxaemia and hypertension found in pregnant women due to different aetiologies.

Adult↗
PubMed1994

Uric acid, anion gap and urea concentration in the diagnostic approach to hyponatremia.

We analyzed the serum anion gap (AG = sodium plus potassium minus chloride plus bicarbonate, N = 11-21 mEq/l), serum uric acid and urea concentrations in hyponatremia of various origins. We found that characteristic chemical patterns emerged in association with different hypotonic states: Low uric acid concentration was typically observed in the SIADH and in hyponatremia related to hypopituitarism. The same observation was also frequently noted in hyponatremia secondary to diuretics or to polydypsia. In the SIADH, we observed a decrease in the AG but to a greater extent (-26%) than one would expect from the simple dilutional effect (-16%). Fifty percent of the patients presented an AG lower than 11 mEq/l. In patients with diuretic-related hyponatremia, one group presented an hypouricemia and a low AG as in SIADH (reflecting volume expansion), in the other group the AG was normal or increased as was uric acid concentration (reflecting volume depletion). In adrenocorticotropin deficiency, hyponatremia was typically associated with a low bicarbonate concentration, a normal AG and hypouricemia. In polydypsic patients with hyponatremia, the AG was usually normal or increased despite sometimes very low sodium levels. Uric acid levels were highly variable, most often decreased. We also noted in these patients that the serum urea levels were correlated with urine osmolality (R = +0.8; p < 0.001), and in 40% of them we observed very low blood urea concentration (0.5-2 mmol/l) at the admission time. In hyponatremia related to cardiac failure or cirrhosis, the AG was usually normal despite mild hypoproteinemia.

Acid-Base Equilibrium↗
PubMed1978

New continuous-flow analysis for simultaneous determination of creatinine and uric acid in 200 microliters of serum without use of a dialyzer.

We present a new method for direct continuous-flow (AutoAnalyzer II) measurement of serum creatinine and uric acid. The manifold is simple, inexpensive, and can be constructed in the laboratory. Only 200 microliters of serum is needed; analysis rate is 60 samples per hour. The incorporation of sodium dodecyl sulfate and the simultaneous provision of blank subtraction make it possible to omit the dialysis step. Our method does not require the linearizer, since instrument response and concentration of creatinine and uric acid are linearly related to 200 and 120 mg/liter, respectively. The percentages of steady state, interaction, and recovery are acceptable, Precision is excellent and the results obtained from the new method correlate well with those obtained by the comparison methods. Interferences are few and, when encountered, are generally smaller than in the modified Technicon method. Marked hemolysis interferes only with the uric acid assay; marked turbidity has no effect on results for creatinine. Icteric serum with total bilirubin of 50 and 100 mg/liter interferes significantly with results for creatinine and uric acid, respectively, by the new method.

Autoanalysis↗
PubMed2001

Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980-1994. National Integrated Projects for Prospective Observation of Non-communicable Diseases and its Trend in the Aged.

Although elevated serum uric acid has been associated with an increased risk of cardiovascular disease, its importance as a risk factor is still controversial. The authors examined the relationship between serum uric acid levels and death from all causes, including cardiovascular disease and stroke. The baseline data were collected in the National Cardiovascular Survey in 1980. The survey was carried out for all household members aged 30 years or older in 300 districts, which were randomly selected throughout Japan. The number who participated in the survey was 10,897. The vital status was ascertained in 1994. Finally, 8172 subjects were available for the analyses. There were 108,284 person-years of follow-up, and 960 deaths from all causes, 249 deaths from cardiovascular disease, and 174 deaths from stroke. After adjustment for age and other cardiovascular disease risk factors, uric acid levels were not associated with mortality from all causes, cardiovascular disease, or stroke. These findings indicate that serum uric acid levels are not related to increased risk for death from all causes, including cardiovascular disease and stroke in a Japanese population.

Adult↗
PubMed2000

High total antioxidant activity and uric acid in tracheobronchial aspirate fluid of preterm infants during oxidative stress: an adaptive response to hyperoxia?

The effect of O2 exposure, expressed by mean daily fractional inspired oxygen concentration (FiO2), was evaluated during the first 6 d of life in the tracheobronchial aspirate fluid of 16 mechanically ventilated preterm infants in terms of both antioxidant response and oxidative damage, by measuring total antioxidant activity, uric acid concentrations and protein carbonyl content. Each day linear regression analysis was performed and a positive correlation was found between total antioxidant activity and FiO2 during the study period, especially on day 2 of life (r = 0.91, p < 0.0001), but uric acid correlated only in the first 3 d, especially on the 2nd day (r = 0.83, p < 0.0001). No correlation was found between carbonyl content and FiO2. The highest values of total antioxidant activity (416 and 790 micromol l(-1)) were found in 2 babies ventilated with highest FiO2: 1 and 0.80, respectively. Total antioxidant activity was not detectable or was very low in the babies not requiring O2 therapy. The highest value of uric acid (270 micromol l(-1)) was found in the baby ventilated with 100% oxygen. Uric acid concentrations obtained in these babies were much higher then those reported in the bronchoalveolar lavage fluid of adults. Preterm babies seem to have an antioxidant response in the tracheobronchial aspirate fluid following an oxidative stress and uric acid may be physiologically important as an antioxidant of the respiratory tract, especially during the first days of life.

Antioxidants↗
PubMed1987

Measurement of allantoin and uric acid in human body fluids. A potential index of free-radical reactions in vivo?

Free-radical attack upon uric acid generates allantoin [Ames, Cathcart, Schwiers & Hochstein (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6858-6862]. Methods are described for the accurate measurement of uric acid and allantoin in human body fluids. The concentrations of uric acid and allantoin in human serum and synovial fluid are reported. It is suggested that measurement of changes in allantoin concentration may be a useful index of free-radical reactions taking place in vivo.

Allantoin↗
PubMed1982

Serum uric acid as a risk factor for stroke in a fishing village of rural southern Japan.

In order to clarify the risk factors for stroke from an epidemiological viewpoint, 314 men (aged 50-79) in the fishing village of Ushibuka were evaluated over an 8-year period (1970-1978) by means of multivariate analysis. At the systematic re-examination in 1970, the following 11 variables were determined: age, systolic blood pressure, electrocardiographic (ECG) abnormalities, serum cholesterol, serum triglyceride, serum alpha-lipoprotein fraction, serum albumin, serum uric acid, drinking habits, smoking habits and body mass index. Thirty men experienced stroke during the 8-year period. The mean value of age, systolic blood pressure and serum uric acid were significantly higher in men who experienced stroke, while serum cholesterol, triglyceride, alpha-lipoprotein fraction and albumin were not seen as statistically significant. The high level of serum uric acid correlated with the high incidence of stroke. According to stepwise discriminant analysis of the 11 variables. ECG abnormalities, systolic blood pressure and serum uric acid discriminated 73.9% of the men who experienced stroke. In conclusion, a high serum uric acid concentration is noted to be an important risk factor for stroke in the fishing village of Ushibuka where high intake of fish protein is common.

Aged↗
PubMed1991

Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.

Several points regarding the use of drugs to lower uric acid levels deserve emphasis. First, these agents are not useful in the management of acute gout. Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this. Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.

Arthritis, Gouty↗