Reference range: 4.0-8.5 mg/dL or 237-506 mmol/L for males >17 years old; 2.7-7.3 mg/dL or 161-434 mmol/L for females >17 years old
Uric acid is the metabolic end-product of the purine bases of DNA. In humans, uric acid is not metabolized further and is eliminated unchanged by renal excretion (the net result of filtration, secretion, and reabsorption). It is completely filtered at the renal glomerulus and is almost completely reabsorbed. Most excreted uric acid (80% to 86%) is the result of active tubular secretion at the distal end of the proximal convoluted tubule.
As urine becomes more alkaline, more uric acid is excreted because the percentage of ionized uric acid molecules increases. Conversely, reabsorption of uric acid within the proximal tubule is enhanced and uric acid excretion is suppressed as urine becomes more acidic.
When serum uric acid exceeds the upper limit of the reference range, the biochemical diagnosis of hyperuricemia can be made. Hyperuricemia can result from an overproduction of purines and/or reduced renal clearance of uric acid. When specific factors affecting the normal disposition of uric acid cannot be identified, the problem is diagnosed as primary hyperuricemia. When specific factors can be identified, the problem is referred to as secondary hyperuricemia.
As the serum urate concentration increases above the upper limit of the reference range, the risk of developing clinical signs and symptoms of gouty arthritis, renal stones, uric acid nephropathy, and subcutaneous tophaceous deposits increases. However, many hyperuricemic patients are asymptomatic. If a patient is hyperuricemic, it is important to determine if there are potential causes of false laboratory test elevation and contributing extrinsic factors.
Medications via 1) decreased renal excretion resulting from drug-induced renal dysfunction; 2) decreased renal excretion resulting from drug competition with uric acid for secretion within the kidney tubules; and 3) rapid destruction of large numbers of cells from anti-neoplastic therapy.
Diet. High-protein weight-reduction programs can greatly increase the amount of ingested purines and subsequent uric acid production.
Endogenous causes of hyperuricemia include diseases, abnormal physiological conditions that may or may not be disease related, and genetic abnormalities. Diseases include 1) renal diseases (e.g., renal failure); 2) disorders associated with increased destruction of nucleoproteins; and 3) endocrine abnormalities (e.g., hypothyroidism, hypoparathyroidism, pseudohypoparathyroidism, nephrogenic diabetes insidious, and Addison disease).
Predisposing abnormal physiological conditions include shock, hypoxia, lactic acidosis, diabetic ketoacidosis, alcoholic ketosis, and strenuous muscular exercise.
Genetic abnormalities include Lesch-Nyhan syndrome, gout with partial absence of the enzyme hypoxanthine guanine phosphoribosyltransferase, increased phosphoribosyl pyrophosphate P-ribose-PP synthetase, and glycogen storage disease type I.