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Uric Acid

Uric acid is an end product of purine metabolism. About one?half of the total body pool turns over each day, partly by urinary excretion and partly through destruction in the intestinal tract. Men usually have levels about 1 mg/dL higher than women of the same age. After menopause, serum uric acid levels in women approach those of men. Newborns generally have elevated uric acid levels.

Gout is a disorder of purine metabolism, characterized by a sudden onset acute arthritis, resulting from deposition of monosodium urate crystals in connective tissues, articular cartilage and synovial fluid. It is one of the most common rheumatic diseases of adulthood, with a self-reported prevalence in the US of 3.9% of adults. The classic presentation is severe pain in the foot, especially the great toe, which is known as podagra. Gout onset often occurs at night and may be associated with such severe pain that the patient cannot wear a shoe. Gout can present in other joints such as the elbow, wrist, foot, arch, ankle, or finger and can present as mono, oligo or polyarticular arthritis. The initial episode usually subsides within 3 to 10 days, even without treatment.

Hyperuricemia is defined as a serum uric acid level of more than 6.8 mg/dL or 7.0 mgdL in men or more than 6.0 mg/dL in women. Most patients with hyperuricemia are asymptomatic and never develop gout. The presence or absence of hyperuricemia is not diagnostic of gout. A patient with gout may have a normal uric acid level at the time of presentation. Persistent elevation of serum uric acid above 7 mg/dL in males and 6 mg/dL in females is associated with renal complications.

Excess uric acid is deposited in the synovium causing arthritis. The best way to diagnose gout is to identify uric acid crystals in synovial fluid. Even in the absence of active joint effusions, gout and pseudogout can be diagnosed from synovial fluid.

In their 2012 guidelines, the American College of Rheumatology recommended that the goal of urate lowering therapy is to achieve a serum urate level target of 6 mg/dl (0.36 mmol/L) or less in patients with gout. A target level below 5 mg/dL (0.30 mmol/L) may be necessary in some patients to durably improve signs and symptoms of gout (Arthritis Care & Research Vol. 64, No. 10, October 2012, pp 1431–1446). The American College of Rheumatology also recommends regular monitoring of serum urate every 2–5 weeks during titration of urate lowering therapy and serial monitoring every 6 months once the serum urate target is achieved.

Similar evidence based recommendations have also been made by the multinational 3e initiative (Sivera F, et al. Ann Rheum Dis 2013;0:1–8. doi:10.1136/annrheumdis-2013-203325)

Not all patients with elevated uric acid have gout. Elevated serum uric acid also occurs with chronic renal disease, hypertension, hyperlipidemia, diabetes mellitus, obesity, atherosclerosis, and eclampsia. Diseases associated with increased cell turnover such as leukemia, lymphoma, and psoriasis may produce hyperuricemia. Ethanol consumption can also raise serum uric acid levels. Chemotherapy and radiation therapy may cause the release of large amounts of uric acid from necrotic tumor cells. Certain medications reduce the excretion of uric acid including thiazide diuretics, loop diuretics, low dose aspirin, cyclosporine, niacin, ethambutol, pyrazinamide, and didanosine.

Elevated uric acid levels are commonly encountered in patients with essential hypertension. Asymptomatic hyperuricemia may even precede the diagnosis and treatment of essential hypertension. Previous dogma suggested that uric acid was simply a marker of other coronary disease risk factors such as obesity, hyperlipidemia, and diabetes mellitus. However, a recent multivariate analysis of 3900 hypertensive people in the NHANES III database showed that raised serum uric acid is independently associated with a higher sex and age adjusted risk of heart attack and stroke (Lancet 1998; 352:670-1). Serum uric acid increases as arterial blood pressure rises, possibly related to reduced renal blood flow. Elevated uric acid is also associated with low-density lipoprotein (LDL) oxidation and subsequent vascular injury. Rising uric acid levels in hypertensive patients may be an early indicator of cardiac and renal disease.

Low levels of uric acid can be seen in patients with liver disease, malnutrition, Fanconi syndrome, acute intermittent porphyria, hemochromatosis, and SIADH.Many medications can reduce uric acid levels including high dose salicylate, corticosteroids, allopurinol, Probenicid, and massive doses of vitamin C.

Serum uric acid can also be used to differentiate diabetes insipidus from psychogenic polydipsia. Patients with diabetes insipidus usually have serum uric acid levels above 5 mg/dL while patients with psychogenic polydipsia have levels below 5 mg/dL.

Uric acid has a non-normal distribution in plasma in most populations. The solubility limit of urate in body fluids corresponds to a serum urate concentration of 7.0 mg/dL (416 micromol/L), as measured by automated enzymatic (uricase) methods. These values are approximately 1 mg/dL (60 micromol/L) lower than those obtained with colorimetric methods. A recent study recommended that the upper limit of normal for uric acid should be set at 6.8 mg/dL (J Rheumatol 2009;36:1287-9).

Rasburicase is a recombinant uric acid oxidase that is used to rapidly reduce plasma uric acid levels in patients with hyperuricemia due to tumor lysis syndrome. Rasburicase converts urate to allantoin and hydrogen preroxide. Allantoin is water soluble and rapidly excreted by the kidney.

Rasburicase continues to degrade uric acid in vitro. If a blood sample is collected and held at room temperature for one hour before testing, uric acid is decreased by 20%. If a patient is receiving rasburicase, blood samples for measurement of uric acid should be collected in pre-chilled heparinized tubes and immediately placed in ice for transportation to the laboratory. Ideally, specimens should be centrifuged in a refrigerated centrifuge. Under these conditions, uric acid levels are stable up to 4 hours.


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