August, 2012

VOL 2 ISSUE 6

CHRONICLES IN CHOLESTEROL
An Insiders Guide to State of The Art Cardiovascular Prevention Laboratory Testing Available From Everest Clinical Laboratories
High uric acid level (hyperuricemia) is an excessive concentration of uric acid in your blood. Uric acid is waste produced during the breakdown of purine, a substance found in many foods. Uric acid normally passes through the kidneys and is eliminated in urine. A high uric acid level may not cause problems. However, some people develop gout, kidney stones or kidney failure due to high uric acid levels. A high uric acid level may appear prior to the development of high blood pressure, heart disease or chronic kidney disease. But it's often unclear whether a high uric acid level is a direct cause or merely an early warning sign of 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, dried peas 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 the kidney. 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.

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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VOL 2 ISSUE 6

Workup of Elevated Uric Acid CBC count: Values may be abnormal in patients with hemolytic anemia, hematologic malignancies, or lead poisoning. Electrolytes, BUN, and serum creatinine values: These are abnormal in patients with acidosis or renal disease. Liver function tests Part of the general workup for patients with a possible malignancy or metabolic disorders. 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 storage diseases. Lipid profile: Results are abnormal in those with dyslipidemia. Calcium and phosphate levels: This measurement is needed for the workup of hyperparathyroidism, 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 acid excretion may be needed. The estimation of uric acid excretion is recommended in young males who are hyperuricemic, females who are premenopausal, people with a serum uric acid value greater than 11 mg/dL, and patients with gout. One protocol recommends obtaining two 24-hour urine collections for creatinine clearance and uric acid excretion. The first collection is performed while patients are on their 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 24hour urine collection performed on the last day, followed by a serum creatinine and uric acid evaluation. Depending on the 24-hour urine uric acid levels before the purine-restricted diet and after the purine-restricted diet, patients who are hyperuricemic can be categorized into 3 groups.

High-purine intake - Prediet value greater than 6 mmol/d, postdiet value less than 4 mmol/d Overproducers - Prediet value greater than 6 mmol/d, postdiet value greater than 4.5 mmol/d Underexcretors - Prediet value less than 6 mmol/d, postdiet value less than 2 mmol/d Fractional excretion of urate on a low-purine diet This test should be used to investigate the degree of underexcretion in patients with hyperuricemia or gout in patients for whom the cause cannot be determined. The fractional excretion of urate is calculated by the following formula: Fractional excretion of urate = [(urine uric acid)*(serum creatinine)*(100%)]/[(serum uric acid)*(urine creatinine)] The reference intervals for patients on a low-purine diet and normal renal function are as follows: Males - 7-9.5% Females - 10-14% Children - 15-22% Values less than the lower limits of the reference range indicate underexcretion. The formula also circumvents any inaccuracy that may have occurred during urine collection. Spot urine ratio of uric acid to creatinine

If a 24-hour urine collection is not possible, measure the ratio of uric acid to creatinine from a spot urine collection. A ratio greater than 0.8 indicates overproduction. The ratio also helps differentiate acute uric acid nephropathy from the hyperuricemia that occurs secondary to renal failure. The ratio is greater than 0.9 in acute uric acid nephropathy and usually less than 0.7 in hyperuricemia secondary to renal insufficiency.

An increased serum LDH level is suggestive of a large tumor burden and correlates with risk. Uric acid and sodium monourate crystals may be observed. Uric acid levels in the urine may be as high as 150200 mg/dL. A random ratio of urinary uric acid to creatinine higher than 1 is also suggestive of acute uric acid nephropathy. A disproportionate elevation in serum uric acid levels also can be a diagnostic clue. Elevated serum and urinary uric acid levels correlate with the frequency of nephrolithiasis, and 50% of patients with serum uric acid levels greater than 13 mg/dL or urinary uric acid secretion higher than 1100 mg/d will form stones.

By Spencer Kroll MD PhD National Lipid Association Board Certified Board of Directors, Northeast Lipid Association