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CHRONICLES IN CHOLESTEROLAn Insiders Guide to State of The Art Cardiovascular

Prevention Laboratory Testing Available From

Everest Clinical Laboratories

High uric acid level (hyperuricemia) is an excessiveconcentration of uric acid in your blood. Uric acid iswaste produced during the breakdown of purine, asubstance found in many foods. Uric acid normallypasses through the kidneys and is eliminated in urine.

A high uric acid level may not cause problems.However, some people develop gout, kidney stones orkidney failure due to high uric acid levels. A high uricacid level may appear prior to the development of high

blood pressure, heart disease or chronic kidneydisease. But it's often unclear whether a high uric acidlevel is a direct cause or merely an early warning signof these conditions.

Causes of High Uric Acid

Diuretics such as thiazides

Alcohol consumption especially beer

Excessive caffeine consumption

Genetic predisposition

Hodgkin's lymphoma

Hypothyroidism

Leukemia

Niacin, or vitamin B-3 Non-Hodgkin's lymphoma

Obesity

Psoriasis

Purine-rich diet organ meat, game meat,anchovies, herring, gravy, dried beans, driedpeas and other foods

Some immunosuppressants

Fructose?

Uric acid is the relatively water-insoluble end product of

purine nucleotide metabolism. It poses a special problem

for humans because of its limited solubility, particularly in

the acidic environment of the distal nephron of thekidney. It is problematic because humans do not possess the

enzyme uricase, which converts uric acid into the more

soluble compound allantoin. Three forms of kidney disease

have been attributed to excess uric acid: acute uric acid

nephropathy, chronic urate nephropathy, and uric acid

nephrolithiasis. These disorders share the common element

of excess uric acid or urate deposition, although the clinical

features vary.

August, 2012 VOL 2 ISSUE 6

In This Issue: Uric Acid

Gout risk was 74% higher among women who

drank a serving of sweetened soft drinks each day

than those who drank less than one serving per

month, a 2010 analysis of the 79,000-participant

Nurses Health Study found. Diet soda didnt

cause gout to rise.

Men who ate the most seafood were 50% more

likely to develop gout than those who ate the

least.

Anchovies, herring, redfish (ocean perch),

sardines and tuna are among proteins that cause

gout pain and should be limited to 4-6 ounces per

day

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Workup of Elevated Uric Acid

CBC count: Values may be abnormal in patients with hemolytic anemia, hematologicmalignancies, or lead poisoning.

Electrolytes, BUN, and serum creatinine values: These are abnormal in patients withacidosis or renal disease.

Liver function tests

Part of the general workup for patients with a possible malignancy or metabolicdisorders.

The results are useful as a baseline if allopurinol is used for treatment.

Serum glucose level: This may be abnormal in patients with diabetes or glycogen storagediseases.

Lipid profile: Results are abnormal in those with dyslipidemia.

Calcium and phosphate levels: This measurement is needed for the workup ofhyperparathyroidism, sarcoidosis, myeloma, and renal disease.

Thyroid-stimulating hormone level: Obtain this value to help rule out hypothyroidism.

Urinary uric acid excretion

If uric acid levels are found to be persistently elevated, an estimation of total uric acidexcretion may be needed. The estimation of uric acid excretion is recommended inyoung males who are hyperuricemic, females who are premenopausal, people with aserum uric acid value greater than 11 mg/dL, and patients with gout.

One protocol recommends obtaining two 24-hour urine collections for creatinineclearance and uric acid excretion. The first collection is performed while patients are ontheir usual diet and alcohol intake. At the end of the first 24-hour collection, serum

creatinine and urate levels are checked for an estimation of the creatinine clearance.The patient then goes on a low-purine, alcohol-free diet for 6 days, with a repeat 24-hour urine collection performed on the last day, followed by a serum creatinine and uricacid evaluation.

Depending on the 24-hour urine uric acid levels before the purine-restricted diet andafter the purine-restricted diet, patients who are hyperuricemic can be categorized into3 groups.

High-purine intake - Prediet value greater than 6 mmol/d, postdiet value less than 4mmol/d

Overproducers - Prediet value greater than 6 mmol/d, postdiet value greater than 4.5mmol/d

Underexcretors - Prediet value less than 6 mmol/d, postdiet value less than 2mmol/d

Fractional excretion of urate on a low-purine diet

This test should be used to investigate the degree of underexcretion in patients withhyperuricemia or gout in patients for whom the cause cannot be determined.

The fractional excretion of urate is calculated by the following formula: Fractionalexcretion of urate = [(urine uric acid)*(serum creatinine)*(100%)]/[(serum uricacid)*(urine creatinine)]

The reference intervals for patients on a low-purine diet and normal renal function areas follows:

Males - 7-9.5%Females - 10-14%Children - 15-22%

Values less than the l ower limits of the reference range indicate underexcretion. Theformula also circumvents any inaccuracy that may have occurred during urinecollection.

Spot urine ratio of uric acid to creatinine

If a 24-hour urine collection is not possible, measure the ratio of uric acid to creatininefrom a spot urine collection. A ratio greater than 0.8 indicates overproduction.

The ratio also helps differentiate acute uric acid nephropathy from the hyperuricemiathat occurs secondary to renal failure. The ratio is greater than 0.9 in acute uric acidnephropathy and usually less than 0.7 i n hyperuricemia secondary to renalinsufficiency.

By Spencer Kroll MD PhD

National Lipid Association Board Certified

Board of Directors, Northeast Lipid Association

August, 2012 VOL 2 ISSUE 6

An increased serum LDH level is suggestive of alarge tumor burden and correlates with risk.

Uric acid and sodium monourate crystals may beobserved.

Uric acid levels in the urine may be as high as 150-200 mg/dL.

A random ratio of urinary uric acid to creatininehigher than 1 is also suggestive of acute uric acidnephropathy.

A disproportionate elevation in serum uric acid levelsalso can be a diagnostic clue.

Elevated serum and urinary uric acid levels correlate

with the frequency of nephrolithiasis, and 50% ofpatients with serum uric acid levels greater than 13mg/dL or urinary uric acid secretion higher than 1100mg/d will form stones.