Test Serum Uric Acid Levels

Test Serum Uric Acid Levels: Overview

The uric acid test is ordered when a doctor suspects high levels of uric acid in the blood.

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In humans and higher primates, uric acid is the final oxidation (breakdown) product of purine metabolism and is excreted in urine.  In humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5-25% of humans impaired renal (kidney) excretion leads to hyperuricemia.

Many drugs can increase or decrease the level of uric acid.  In particular, diuretic drugs such as thiazide drugs can cause uric acid levels to go up.

Aspirin (and other salicylates) have varying effects on uric acid.  At low aspirin levels (as may occur in persons taking aspirin only occasionally), aspirin can increase blood uric acid.  On the other hand, in high doses (as may be used to treat rheumatoid arthritis), aspirin actually lowers the concentration of uric acid.

For people who have uric acid kidney stones or gout, foods that are high in purine content should be avoided, including organ meats (like liver and kidneys), sardines and anchovies.  Alcohol also should be avoided, because it slows down the removal of uric acid from the body.  Fasting, a starvation diet, and strenuous exercise all raise uric acid levels.

Why it is Recommended

The uric acid test is used to learn whether the body might be breaking down cells too quickly or not getting rid of uric acid quickly enough.

Some patients with high levels of uric acid have a disease called gout, which is an inherited disorder that affects purine breakdown.  Patients with gout suffer from joint pain, most often in their toes but in other joints as well.

The test also is ordered when a patient has undergone chemotherapy or radiation, to see if uric acid levels are getting dangerously high.

The test may also be ordered if a patient appears to have failing kidneys.

Expected Outcome

In human blood plasma, the reference range of uric acid is between 3.6mg/dL (~214µmol/L) and 8.3mg/dL (~494µmol/L) (1mg/dL=59.48 µmol/L).  This range is considered normal by the American Medical Association.  Uric acid concentrations in blood plasma above and below the normal range are known, respectively, as hyperuricemia and hypouricemia.  Similarly, uric acid concentrations in urine above and below normal are known as hyperuricosuria and hypouricosuria.  Such abnormal concentrations of uric acid are not medical conditions, but are associated with a variety of medical conditions.

Higher than normal uric acid levels mean that the body is not handling the breakdown of purines well.  The doctor will need to determine whether the cause is over-production of uric acid, or the body being unable to clear away the uric acid.

HIGH URIC ACID

Elevated serum uric acid (hyperuricemia) can result from high intake of purine-rich foods, and/or impaired excretion by the kidneys.  Saturation levels of uric acid in blood may result in one form of kidney stones when the urate crystallizes in the kidney.  These uric acid stones are radiolucent and so do not appear on an abdominal plain x-ray or CT scan.  Their presence must be diagnosed by ultrasound for this reason.  Very large stones may be detected on X-ray by their displacement of the surrounding kidney tissues.  Uric acid can also form crystals or kidney stones that can damage the kidneys.

Patients who have high uric acid levels are sometimes put on a drug regimen to help lower uric acid levels.

Gout
Excess serum accumulation of uric acid can lead to a type of arthritis known as gout.  This painful condition is the result of needle-like crystals of uric acid precipitating in joints and capillaries.

Gout can occur where serum uric acid levels are as low as 6mg/dL (~357µmol/L), but an individual can have serum values as high as 9.6mg/dL (~565µmol/L) and not have gout.  One treatment for gout has been administration of Lithium salts; lithium urate is more soluble.

Although the uric acid test cannot definitively diagnose gout, a test for monosodium urate in synovial fluid (joint fluid) can.

Cardiovascular Disease
Although uric acid can act as an antioxidant, excess serum accumulation is often associated with cardiovascular disease.  It is not known whether this is causative (e.g. by acting as a prooxidant ) or a protective reaction taking advantage of urate's antioxidant properties.

Diabetes
The association of high serum uric acid with insulin resistance has been known since the early part of the 20th century.  Nevertheless, recognition of high serum uric acid as a risk factor for diabetes has been a matter of debate.  In fact, hyperuricemia has always been presumed to be a consequence of insulin resistance rather than its precursor.  However, it was shown in a prospective follow-up study that high serum uric acid is associated with higher risk of type 2 diabetes independent of obesity, dyslipidemia, and hypertension.  [Dehghan A et al, February 2008.  "High serum uric acid as a novel risk factor for type 2 diabetes".  Diabetes Care 31 (2): pp361-2]

Metabolic Syndrome
Hyperuricemia is associated with components of metabolic syndrome and it has been shown in a recent study that fructose-induced hyperuricemia may play a pathogenic role in metabolic syndrome.  This is consistent with the increased consumption in recent decades of fructose-containing beverages (such as fruit juices and soft drinks sweetened with sugar and high-fructose corn syrup) and the epidemic of diabetes and obesity.  [Nakagawa T et al, March 2006.  "A causal role for uric acid in fructose-induced metabolic syndrome".  American Journal of Physiology.  Renal Physiology 290 (3): F625-31.]

Uric Acid Stone formation
Uric acid stones, which form in the absence of a secondary cause such as chronic diarrhea, vigorous exercise, dehydration, and animal protein loading, are believed to be secondary to obesity and insulin resistance seen in metabolic syndrome.  Increased dietary acid leads to increased endogenous acid production in the liver and muscles which in turn leads to an increased acid load to the kidneys.  This load is handled more poorly because of renal fat infiltration and insulin resistance which are believed to impair ammonia excretion (a buffer).  The urine is therefore quite acidic and uric acid becomes insoluble, crystallizes and stones form.  In addition, naturally present promotor and inhibitor factors may be affected.  This explains the high prevalence of uric stones and unusually acidic urine seen in patients with type 2 diabetes.  Uric acid crystals can also promote the formation of calcium oxalate stones, acting as "seed crystals" (heterogeneous nucleation.)

Lesch-Nyhan Syndrome
An extremely rare inherited disorder, also associated with very high serum uric acid levels, causing spasticity, involuntary movement and cognitive retardation as well as manifestations of gout.

LOW URIC ACID

Low levels of uric acid in the blood are seen much less commonly than high levels and are seldom considered cause for concern.  Although low values can be associated with some kinds of liver or kidney diseases, exposure to toxic compounds, and rarely as the result of an inherited metabolic defect, these conditions are typically identified by other tests and symptoms and not by an isolated low uric acid result.

Multiple Sclerosis
Lower serum values of uric acid have been associated with Multiple Sclerosis.  Multiple sclerosis (MS) patients have been found to have serum levels ~194µmol/L, with patients in relapse averaging ~160µmol/L and patients in remission averaging ~230µmol/L.  Serum uric acid in healthy controls was found to be ~290µmol/L.

A 1998 study completed a statistical analysis of 20 million patient records, comparing serum uric acid values in patients with gout and patients with multiple sclerosis.  Almost no overlap between the groups was found.  [Hooper DC et al, January 1998.  "Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis".  Proceedings of the National Academy of Sciences of the United States of America 95 (2): pp675-80]

A 2006 study found that elevation of serum uric acid values in multiple sclerosis patients, by oral supplementation with inosine, resulted in lower relapse rates, and no adverse effects.  [Toncev G, October 2006.  "Therapeutic value of serum uric acid levels increasing in the treatment of multiple sclerosis".  Vojnosanitetski Pregled 63 (10): pp879-82]

Oxidative Stress
Uric acid may be a marker of oxidative stress, and may have a potential therapeutic role as an antioxidant.  On the other hand, like other strong reducing substances such as ascorbate, uric acid can also act as a prooxidant, particularly at elevated levels.  Thus, it is unclear whether elevated levels of uric acid in diseases associated with oxidative stress such as stroke and atherosclerosis are a protective response or a primary cause.

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Test Serum Uric Acid Levels:

Test Serum Uric Acid Levels can help with the following:

Autoimmune

Multiple Sclerosis

Reports from researchers suggest that low uric acid levels are associated with increased frequency and longer bouts of multiple sclerosis.  Uric acid levels should be monitored and, if low, raised by supplemental molybdenum and reducing any copper toxicity.

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