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

Uric acid stones, which represent 5-10% of all renal calculi in the United States, also result from uric acid precipitation in the collecting system. Uric acid stones are related to uric acid exceeding its solubility in the urine; thus, patients with hyperuricosuria have an increased risk of uric acid nephrolithiasis. Urine oversaturation with uric acid and subsequent crystal formation is determined largely by urinary pH. Individuals who form uric acid stones tend to excrete less ammonium, which contributes directly to low urinary pH. In addition, persons with gout and those who form stones, in particular, have a reduced postprandial alkaline tide (alkaline urinary pH). Lead exposure may affect urate excretion by the kidney, leading to chronic hyperuricemia and kidney disease. Renal excretion of uric acid involves 4 pathways: filtration, reabsorption, secretion, and postsecretory reabsorption. Urate is freely filtered at the glomerulus. An active anion-exchange process in the early proximal convoluted tubule reabsorbs most of it. Most urinary uric acid appears to be derived from tubular secretion, possibly from the S2 segment of the proximal tubule. Overall, 98100% of filtered urate is reabsorbed; 6-10% is secreted, ultimately appearing in the final urine. The major factors that affect urate excretion are the tubular fluid pH, the tubular fluid flow rate, and renal blood flow. The first 2 factors primarily diminish uric acid and urate precipitation in the collecting ducts, while the third is important in urate secretion. In disorders such as sickle cell disease, hypertension, and eclampsia, hyperuricemia out of proportion with decreases in glomerular filtration result from decreased renal blood flow. Organic acids, such as lactic acid and ketoacids, also can impair the proximal secretion of uric acid.

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