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At least 19 recordsLinked to original sources
PubMed1979

Physiologic determinants of serum urate levels in adolescence.

During adolescence, serum urate increases and adult levels are achieved. Physiologic factors related to serum urate were investigated in a nationally representative population of 6,768 youths aged 12 to 17 years (the US Health Examination Survey). Serum urate concentration increases markedly from ages 12 to 14 years in males, and levels were related to sexual and skeletal maturation. Although similar relationships were observed in females, the association is less striking, probably because of earlier pubescence, which was not captured in this study, and a pronounced androgenic response. In the later stages of adolescence (ages 15 to 17 years for males and 13 to 17 years for females), body composition (body mass index and skinfold thickness), blood pressure, and hematocrit have stronger relationships than sexual and somatic maturation. These latter relationships are similar to those in adults. This survey affords a portrayal of physiologic interrelationships with serum uric acid during adolescence.

Adolescent↗
PubMed1977

Serum urate in subjects with hypercalcaemic hyperparathyroidism.

A positive correlation was found between serum urate and elevated serum calcium in patients with hypercalcaemic primary hyperparathyroidism. No such correlation was detected in normocalcaemic controls, matched with respect to age and sex. Neither was such a correlation confirmed either in subjects with normalized serum calcium levels after extirpation of parathyroid adenomata, or in subjects with hypercalcaemia due to other conditions than primary hyperparathyroidism, such as various malignancies, sarcoidosis and hyperthyroidism. The positive correlation between elevated serum calcium and serum urate (within normal limits) in subjects with hypercalcaemic hyperparathyroidism is suggested in subjects with hypercalcaemic hyperparathyroidism is suggested to be a clue to the explanation of an association between hyperparathyroidism and urate retention.

Female↗
PubMed1979

[A pilot and a controlled study of the influence of ethambutol on serum urate concentration and uric acid clearance (author's transl)].

Ethambutol is said to be capable of elevating serum urate concentration. This statement was reconsidered in three investigations using strictly supervised administration of ethambutol in a single daily dose of 25 mg. per kg. of body weight: (1) In short term administration 10 healthy subjects received ethambutol for eight days. (2) In a pilot study 13 patients suffering from pulmonary tuberculosis were treated with a triple combination including thambutol for six months. (3) In a controlled trial 23 patients were randomly allocated to one of the following regiments: In the first group patients received ethambutol plus isoniazid plus rifampicin for six months. In the second group patients received streptomycin plus isoniazid plus PAS for three months and thereafter streptomycin plus isoniazid plus ethambutol for another three months. Serum urate concentrations and clearances of uric acid and of creatinine were determined periodically in all subjects. A slight increase in serum urate concentration occurring in long term therapy showed no relation to ethambutol administration, but was obviously dependant on parameters related to the course of the disease in form of increase in body weight and physical activity, or related to the well known syntropy of chronic alcoholism and tuberculosis.

Alcoholism↗
PubMed1977

Serum urate levels between ages 10 and 14: changes in sex trends.

Urate levels were assayed in sera of 292 subjects between 10 and 14 years of age identified through a probability sample of a natural population. The sex trends in serum urate concentrations characteristic of childhood were seen to continue into early adolescence, with girls maintaining slightly higher means. Between 10 and 14 years there was first an overlap of male and female values followed by a reversal of trends, with much higher means in boys. Serum urate concentrations peaked in girls at age 11 and gradually stabilized at lower levels. Boys, on the other hand, showed little age variation in serum urate at 10 and 11 years but by age 12 showed sharp upward trends which continued throughout adolescence. Since age and body weight are known to be important covariates of serum urate, boys were matched to girls of the same age and body weight. Significant sex differences in urate levels persisted (after matching) only for 14-year-old adolescents and thus at this age could not be ascribed to weight differentials. The study highlights a peripubertal phenomenon whose mechanism might be endocrine related.

Adolescent↗
PubMed1977

Effect of increased serum urate levels on virgin rats with no arteriosclerosis versus breeder rats with preexistent arteriosclerosis.

Healthy virgin and breeder rats (Sprague-Dawley) with naturally occurring hypertension and arteriosclerosis were fed 5% oxonic acid and 1% uric acid added to their regular diet for 30 days. Although rats are able to convert uric acid into excretable allantoin, abnormal urinary and serum urate levels appeared. Males and females, virgins and breeders, differed in the severity of their increased urate levels. Animals with elevated urate levels developed hypertension, hyperglycemia, and hypertriglyceridemia, with only slight changes in cholesterol and free fatty acids. The kidneys were greatly enlarged and manifested medullary streaking indicative of urate deposits but were free of significant damage; BUN levels in these animals were abnormally high. Adrenal glands were reduced in size and depleted of lipid, circulating corticosterone levels were subnormal, and thymi were involuted. Serum enzymes CPK and LDH were greatly increased, whereas SGOT and SGPT levels were not elevated. The abnormal urate levels did not induce de novo arterial disease in the formerly healthy virgin rats and did not cause exacerbation of the pre-existing, naturally occurring arteriosclerosis characteristic of repeatedly bred rats. It is suggested that Sprague-Dawley rats are endowed with an especially efficient hepatic and renal capacity to metabolize uric acid. Increased urate levels in rats may have some direct metabolic relationship to the production of hypertension, hyperglycemia, and hypertriglyceridemia.

Animals↗
PubMed1977

Plasma urate and serum deoxycytidylate deaminase measurements for the early diagnosis of pre-eclampsia.

The value of measuring plasma urate and serum deoxycytidylate deaminase (dCMP deaminase) for the early diagnosis of pre-eclampsia has been investigated in 45 patients. A combination of increased blood pressure and increased plasma urate identified 19 patients with a high incidence of fetal and maternal morbidity ascribable to pre-eclampsia. Seventeen of the 19 patients also had an increased serum dCMP deaminase. Serial antenatal observations for a mean period of 104 days (36-179 days) on 33 of the patients demonstrated that plasma urate and serum dCMP deaminase increased together as early changes in the development of pre-eclampsia. In six patients, blood pressure, plasma urate and serum dCMP deaminase all increased but in only one was the rise in blood pressure the first change. Elevations of plasma urate and serum dCMP deaminase are therefore both early features of pre-eclampsia. Serial measurements can give warning of the disorder before the appearance of other clinical features. The change in dCMP deaminase is probably another reflection of early renal involvement in the pre-eclamptic process.

Blood Pressure↗
PubMed2026

Urate-lowering effects of losartan: a meta-analysis of randomised controlled trials and target trial emulation.

Common in hypertensive patients, hyperuricaemia is often exacerbated by guideline-recommended antihypertensive therapies such as thiazide diuretics. Losartan is known as an angiotensin II receptor type 1 antagonist with a uricosuric effect, but the magnitude of its efficacy in lowering urate has not been quantified versus a placebo-reference. We sought to quantify the urate-lowering effect of losartan versus placebo using two complementary approaches. We first conducted a meta-analysis of randomised controlled trials (RCTs) to quantify the effect of losartan on serum urate levels versus placebo. We then applied a target trial emulation framework in the UK Biobank as a secondary source of data and a replication experiment. The meta-analysis of six prospective randomised controlled trials (RCTs), including 1119 losartan-treated patients and 1093 controls, demonstrated that losartan reduced serum urate levels by approximately 0.29 mg/dL relative to placebo (95% CI: -0.46 to -0.12, p = 0.0009). In the target trial emulation, 23 losartan-treated individuals showed a reduction in serum urate of approximately 0.35 mg/dL (95% CI: -0.66 to -0.03, p = 0.03) when compared with 92 matched controls, and after accounting for 12 potential confounders including established urate-lowering therapies. Our results provide evidence for a modest yet consistent urate-lowering potential of losartan. This modest biochemical effect (~0.3 mg/dL) may be an attractive option to mitigate the diuretic-induced urate elevation. Thus, losartan can be considered as a favourable antihypertensive choice for patients managed with diuretics or those who are at risk of hyperuricaemia/gout.

Losartan↗
PubMed1978

A rapid method for the diagnosis of acute uric acid nephropathy.

Acute uric acid nephropathy is a reversible type of renal failure that results from the deposition of uric acid crystals in the collecting tubules. The present study has compared a number of laboratory tests in 5 patients with a clinical diagnosis of this disorder and 27 patients with acute renal failure of other causes. Neither the serum creatinine, BUN, serum urate concentrations, nor the ratio of serum urate:BUN differentiated between these two groups of patients. However, the ratio of uric acid to creatinine concentration on a random urine specimen did differentiate between these two patient populations. All patients with uric acid nephropathy had a ratio greater than 1.0, while all patients with other types of acute renal failure had ratios of less than 1.0.

Acute Kidney Injury↗
PubMed1976

Urate kinetics in hypoxanthine-guanine phosphoribosyltransferase deficiency: their significance for the understanding of gout.

Urate production (miscible urate pool and turnover, daily production, glycine incorporation into urate) and urate excretion (24 hour urinary urate excretion on a purine free diet, renal clearances of urate and creatinine, per cent renal excretion of labelled urate, extra-renal elimination of urate) were measured in members of five families who demonstrated varying degrees of deficiency of the X-linked condition hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. The hemizygous males, all of whom eventually developed symptoms, showed consistent overproduction of urate with a renal excretion of urate that varied from moderately to considerably increased. The nine heterozygotes, of whom seven were asymptomatic, also showed abnormalities of urate production, although all but two had normal serum urate concentrations. The one heterozygote who had developed gouty arthritis had the lowest renal excretory capacity for urate, whereas the one heterozygote who had developed an episode of renal colic had the highest urate clearance. In the heterozygotes with normal serum urate concentrations, the increase urate production was balanced by the renal excretion of urate. This demonstrates the importance of the relation between urate. This demonstrates the importance of the relation-between urate production and urate excretion in determining the clinical expression of abnormal urate metabolism.

Adolescent↗
PubMed1978

Prospective analysis of psoriatic arthritis in patients hospitalized for psoriasis.

Among 77 patients hospitalized with psoriasis, 30 (39%) had psoriatic arthritis. Arthiritis was more frequent (P less than 0.05) in those with extensive psoriasis (grades 3 and 4) than in those with less extensive psoriasis (grade 1 and 2). Temporally, flares in skin and joint disease were not closely related. The Moll-Wright classification of psoriatic arthritis into five clinical groups could be loosely applied to our patients. However, sacroiliitis (present in 33% of the patients) was seen in all five groups and was related to HLA-B27 antigen. Although there was no positive correlation between extent of psoriasis and serum urate level, four patients had gout. Mean serum urate level was higher (P less than 0.05) in females with psoriatic arthritis than in females with psoriasis alone. Antinuclear antibodies were found in 6 of 19 patients with psoriatic arthritis and in none of the 11 patients with psoriasis alone.

Adolescent↗
PubMed1979

Hyperuricaemia in hypertension: role of alcohol.

Hyperuricaemia was present in 18 out of 73 men with untreated mild hypertension and was related significantly to alcohol intake, serum aspartate transaminase activity, and obesity. In the whole group the mean serum urate concentration correlated highly significantly with alcohol intake and activities of serum aspartate and alanine transferases but not with ponderal index, serum creatinine concentration, age, or blood pressure. Hypertension and hyperuricaemia are related at least in part through their common association with frequent alcohol use. A serum urate concentration exceeding 0.5 mmol/l (8--4 mg/100 ml) in a man with untreated hypertension is highly suggestive of heavy alcohol consumption. There was no evidence that hyperuricaemia had a deleterious effect on renal function.

Adult↗
PubMed2026

Timing of OMERACT core domain measurement in gout clinical trials: a systematic review of randomised trials.

AIMS: The Outcome Measures in Rheumatology (OMERACT) initiative has endorsed core domain sets for gout trials. The aims of this study were to evaluate the time points and frequencies at which the gout core domains are measured in existing gout urate-lowering therapy and gout flare trials, and whether all collected measurements were reported. METHODS: Urate-lowering therapy (n = 29) and gout flare randomised clinical trials (n = 14) from 2005 were identified from a prior systematic review of core domain reporting. Data were extracted for the time points and frequencies at which each core domain was measured, as well as whether all collected measurements were reported. RESULTS: In urate-lowering therapy trials, the core domains were measured at seven different frequencies. Serum urate and gout flares were most commonly measured monthly, and tophus burden was most commonly measured three monthly. Reporting of all collected measurements varied, from 24/29 (83%) trials for serum urate to 0/2 (0%) trials for activity limitation. In gout flare trials, core domains were measured at nine different frequencies. Pain, joint tenderness and joint swelling were most commonly measured monthly. Reporting of all collected measurements varied, from 13/14 (93%) trials for pain to 3/8 (37.5%) trials for joint tenderness. CONCLUSION: In both urate-lowering therapy and gout flare trials, there is substantial variability in when the core domains are measured, and reporting of collected measurements is inconsistent. This work provides the foundation for a consensus process to establish standardised time points and frequencies for measuring the OMERACT-endorsed gout core domains.

Gout↗
PubMed2026

Multiple metabolic factors and kidney dysfunction: Causal evidence and translational insights from a mendelian randomization study.

Chronic kidney disease is a major global public health burden. This study investigated the causal effects of systolic blood pressure (SBP), apolipoprotein B (ApoB), and serum urate on renal function and albuminuria, and explored potential mechanistic implications. Two-sample Mendelian randomization (MR) analyses were conducted using large-scale genome-wide association study summary statistics from European populations. Univariable MR estimated total causal effects on estimated glomerular filtration rate (eGFR) and albuminuria. Multivariable MR assessed independent effects of correlated exposures, and 2-step MR evaluated albuminuria as a mediator. Cis-MR analyses were performed to explore target-proximal genetic evidence for lipid-related drug targets. Genetically predicted SBP was causally associated with reduced eGFR, while ApoB was inversely associated with albuminuria risk. serum urate showed no significant causal effects. Multivariable and mediation analyses supported distinct roles of SBP and ApoB, with albuminuria partially mediating the SBP-eGFR association. Cis-MR analyses indicated heterogeneous renal effects of lipid-lowering targets. These findings provide genetic evidence linking SBP to renal dysfunction, suggest that albuminuria may partially mediate the association between SBP and renal function, and highlight the complex renal relevance of lipid-related pathways.

Mendelian Randomization Analysis↗
PubMed1978

Treatment of arterial hypertension with tienilic acid, a new diuretic with uricosuric properties.

Tienilic acid--2,3-dichloro-4-(2-thienyl-carbonyl)phenoxyacetic acid--is a new diuretic with uricosuric properties. Nineteen patients with moderate arterial hypertension were treated for 5 consecutive weeks in a randomized fashion in a double-blind study with either tienilic acid or hydrochlorothiazide. Blood pressure was significantly reduced and to the same degree with both drugs. In 7 of the 11 patients receiving tienilic acid the daily dose was increased from 250 to 500 mg after 2 weeks, and in 2 of the 8 patients taking hydrochlorothiazide the daily dose was increased from 50 to 100 mg. Because of the potent uricosuric action of tienilic acid the mean serum urate concentration decreased from 6.3 to 3.3 mg/dL in the patients taking the drug. In contrast, the patients receiving hydrochlorothiazide the mean serum urate concentration increased from 6.1 to 7.8 mg/dL. Moderate hypokalemia of almost identical degree (mean serum potassium values 3.6 and 3.5 mmol/L) and mild metabolic alkalosis were observed in both groups. Tienilic acid had a marked hypocalciuric effect, which was of the same magnitude as the observed with hydrochlorothiazide. During the 5 weeks of treatment no significant change in renal or liver function was observed in either group. There were no hematologic complications and the drug was remarkably well tolerated. Tienilic acid, because of its unique character as a diuretic, hypouricemic and antihypertensive agent, should become the preferred drug for the treatment of arterial hypertension.

Adult↗
PubMed1976

The pathogenesis of coronary artery disease. A possible role for methionine metabolism.

Homocystinuria, an abnormality of methionine metabolism is associated with severe vascular disease in infancy and childhood. Homocysteine is formed during the metabolism of methionine and accumulations of this and of cysteine-homocysteine mixed disulfide in the plasma indicate a partial block in the methionine degradation pathway. Methionine metabolism was investigated in 25 patients aged under 50 with angiographically proved coronary artery disease and in 22 control patients, of whom 17 had normal coronary arteries at angiography and 5 were healthy volunteers. After an overnight fast, venous blood was drawn before and 4 h after oral L-methionine, 100 mg/kg. Plasma methionine levels at 4 h were not different in the two groups, but there were significant differences in the levels of cysteine-homocysteine mixed disulfide. This was detected in 5 of 22 in the noncoronary group and in higher concentration in 17 of 25 coronary patients (P less than 0-01). Age, weight, height, body-mass index, glucose tolerance, fasting serum urate, and triglycerides were not different, but serum cholesterol was higher in the coronary patients (P lessthan 0.01). These results suggest a reduced ability to metabolise homocysteine in some patients with premature coronary artery disease when this pathway is stressed.

Coronary Disease↗