Serum urate

Prophylactic treatment can be withheld if the first episode of acute gouty arthritis was mild and responded promptly to treatment, the patient s serum urate concentration was only minimally elevated, and the 24-hour urinary uric acid excretion was not excessive (less than 1,000 mg/24 hours on a regular diet). 

Colchicine given in low oral doses (0.5 to 0.6 mg twice daily) may be effective in preventing recurrent arthritis in patients with no evidence of visible tophi and a normal or slightly elevated serum urate concentration. The oral dose should be reduced to no more than 0.6 mg daily or every other day in patients with renal or hepatic dysfunction. Treated patients who sense the onset of an acute attack should increase the dose to 1 mg every 2 hours in most instances, the attack aborts after 1 or 2 mg. Discontinuation of prophylaxis may be attempted if the serum urate concentration remains normal and the patient is symptom-free for 1 year. 

Unwanted effects of sulfonamide-type diuretics (a) hypokalemia is a consequence of excessive 1C loss in the terminal segments of the distal tubules where increased amounts of Na are available for exchange with 1C (b) hyperglycemia and glycosuria (c) hyper-uricemia-increase in serum urate levels may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system. 

Asymptomatic hyperuricemia Generally, do not use to treat asymptomatic hyperuricemia. Treatment should be considered with persitent hyperuricemia characterized by a serum urate concentration of greater than 13 mg/dL. High serum urate may be nephrotoxic. 

In patients with severely impaired renal function or decreased urate clearance, the plasma half-life of oxipurinol is greatly prolonged. A dose of 100 mg/day or 300 mg twice a week, or less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels. 

Gouty arthritis is an inflammatory response to the deposition of monosodium urate monohydrate crystals secondary to hyperuricemia. It is called monosodium urate crystal deposition disease. Hyperuricemia is a serum urate concentration > 7 mg% in males and >6 mg% in females. Hyperuricemia results from overproduction (10-15% of individuals) or a renal excretion of urate lower than 400 mg uric acid/24 hours (85-90% of individuals). The urate under-excretors have a urate clearance of <6 ml/min or a urate to creatinine clearance ratio of <6%. The combination of a relative excess of dietary purine consumption together with urate under-excretion is often the basis for hyperuricemia. 

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. 

Febuxostat is a potent and selective inhibitor of xanthine oxidase, and thereby reduces the formation of xanthine and uric acid. No other enzymes involved in purine or pyrimidine metabolism are inhibited. In clinical trials, febuxostat at a daily dose of 80 mg or 120 mg was more effective than allopurinol at a standard 300 mg daily dose in lowering serum urate levels. The urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion. 

Iopanoic acid is as potent a uricosuric agent as probenecid and this effect might explain some renal complications aspirin reduces the uricosuric effect but can also impair X-ray visualization because of competition at plasma protein-binding sites. Fluctuations of serum urate after oral cholecystography can interfere with diagnostic tests and even precipitate an attack of gout (578). 

R22. Rosell, M., Regnstrom, J., Kallner, A., and Hellenius, M. L., Serum urate determines antioxidant capacity in middle-aged men—A controlled, randomized diet and exercise intervention study. 

Underexcretion of urate is caused by all diuretics (except spironolactone), aspirin, ethambutol, pyr-azinamide, nicotinic acid, and alcohol (which increases urate synthesis and also causes a rise in blood lactic acid that inhibits tubular secretion of urate). The diagnosis of gout ideally requires the demonstration of negatively birefringent needle-shaped crystals in synovial fluid (monosodium urate monohydrate crystals), not just elevated serum urate. 

Treatment is initiated if the serum urate consistently exceeds 0.6 mmol/1 and the patient has had three or more attacks of acute gout in a year. 

Harris M, Bryant LR, Danaher P, Alloway J. Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis. J Rheumatol 2000 27(12) 2873-6. 

In addition to a rise in serum potassium, timolol increases plasma uric acid concentrations (207). In the TOMHS study, acebutolol increased serum urate by 7 pmol/1 (196). 

In spite of the catabolism of tissue induced by starvation, the serum protein concentration is little affected initially ultimately, a reduction occurs. However, from the beginning, the catabolism of nucleoproteins causes an increased serum urate. Rise in serum urate is exacerbated by the reduced GFR and the competition for excretion from lactate and ketoacids. 

The serum creatinine concentration increases steadily from infancy to puberty parallel with development of skeletal muscle until puberty, there is little difference in the concentration between sexes. The serum urate concentration decreases from its high at birth until age 7 to 10 years, at which time it begins to increase, especially in boys, until about age 16 years. 

Primary gout is a disorder of purine metabolism seen predominantly in men. The condition is multifactorial and involves genetic and nongenetic factors. Occurrence in women is uncommon when it does occur, it is usually found in postmenopausal women. The blood urate concentration of normal men is 1 mg/dL higher than that in women, but this difference disappears after the menopause. Thus, in women, the postmenopausal rise in serum urate levels may increase the risk of developing gout. Gout is very rare in children and adolescents. 

Serum urate levels can be lowered by dietary and lifestyle changes. These include correction of obesity, avoidance of ethanol consumption, and avoidance of high-purine foods (e.g., organ meats). Psuedogout is a disorder caused by deposition of calcium pyrophosphate dihydrate usually in larger joints such as knee, wrist, and ankle. 

There have been reports in the literature of hypouricemia coincident with specific inborn metabolic errors, but many of these cases are attributable to defects in the kidney leading to failure of renal tubular reabsorption. It was mentioned above that the excretion of uric acid by the Dalmatian coach hound can be attributed to such a mechanism (Fll). Similarly, the hypouricemia found in the Fanconi syndrome (L4) and Wilson s disease (B12) can be attributed to kidney malfunction. These are not true examples of underproduction of oxypurines, including uric acid, since the daily output of uric acid is normal. The large number of healthy people who have extremely low serum urate values, however, may indicate that there are individuals who underproduce oxypurines but suffer no ill effects because of this. The one well-documented inborn error that results in underproduction of uric acid is xanthinuria. It has been reported in relatively few cases, probably because individuals with this metabolic abnormality who suffer no ill effects would not come to the attention of a physician. 

A condition known as pseudogout has been investigated by Kohn et al. (K12). Clinically, their patients appeared to have gouty arthritis. However, the serum urate levels were normal. When fluid from these patients was removed, it was found to contain crystals that were not sodium urate but calcium pyrophosphate. The mechanistic parallels to gout are obvious. 

Uricosuria 4- low serum urate Present Absent Absent... 

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