Uric Acid - Kresser Institute Membership Site

Marker Name: Uric acid

REFERENCE RANGES FOR URIC ACID:

Laboratory reference range: 3.7–8.6 mg/dL

Functional reference range:

Male: 3.7–6 mg/dL

Female: 3.2–5.5 mg/dL

DESCRIPTION:

Uric acid is the end product of purine metabolism, where it serves as a relatively soluble molecule for the excretion of purine molecules in urine. Negligible amounts of uric acid are consumed in the diet; however, consumption of uric acid precursors in the form of purine molecules is substantial.¹ Uric acid may also function as an antioxidant and free radical scavenger.² Historically, uric acid was viewed as a relatively innocuous waste product that only contributed to human disease if the molecule precipitated as uric acid crystals, as seen in gout and urolithiasis. More recently, however, uric acid is believed to contribute to inflammation and oxidative stress.³

Healthy adult men have a total uric acid pool of around 1.2 g, which is about twice the amount that adult women have.⁴ This is presumably due to increased clearance, reduced reabsorption, and a greater number of active renal urate transporters in women versus men. Approximately 60 percent of the total uric acid pool is replaced each day through production and elimination under steady-state conditions.⁴

Most uric acid is produced in the liver from the metabolism of consumed purines, or, to a lesser extent, of purines synthesized by the body. The purine bases guanine and hypoxanthine are metabolized to xanthine, which is, in turn, irreversibly oxidized to uric acid by the xanthine oxidase enzyme. Non-liver tissues produce negligible amounts of uric acid via nonspecific metabolic enzymes.⁴ Two-thirds of uric acid is eliminated from the body through the urine, while the remaining one-third is expelled in the gastrointestinal tract.⁵

Uric acid may be measured in blood or urine. An elevated uric acid level in the blood is called hyperuricemia, while an elevated uric acid level in the urine is called hyperuricosuria. In most cases, uric acid levels in blood will mirror urinary uric acid levels. However, if a person has decreased renal excretion of uric acid, this could cause abnormally high uric acid levels in the blood and abnormally low uric acid levels in the urine. Normally, uric acid levels in the blood are assumed to reflect total body levels of uric acid. Nonetheless, patients with deposits of uric acid crystals and tophi within joints may have more total body uric acid than is reflected in blood samples.

While there is a clear association between blood uric acid levels and the risk of gout, not all patients with elevated blood uric acid levels will develop gout or uric acid crystal deposits.^6,7 Conversely, some patients with gout may not have consistently elevated levels of uric acid in the blood.⁸

Primary hyperuricemia is supersaturated uric acid levels in the presence of an offending drug or coexisting disease that directly elevates uric acid.⁹ Secondary hyperuricemia, on the other hand, may be due to excessive uric acid production, reduced renal clearance of uric acid, or both. Secondary hyperuricemia may be the result of an identifiable genetic disorder, drug, supplement, or environmental insult.¹⁰ The list of causes of secondary hyperuricemia is extensive. Numerous medications, inherited disorders, acquired conditions, and lifestyle diseases may increase blood uric acid levels. While hyperuricemia is clearly associated with chronic kidney disease, hypertension, cardiovascular disease, and insulin resistance, it is not clear whether these elevated uric acid levels are causative or correlative.⁸

An abnormally low level of uric acid in the blood is called hypouricemia; the causes of hypouricemia are almost as numerous as the causes of hyperuricemia. Hypouricemia may be caused by decreased uric acid production, decreased reabsorption in the kidney, or increased oxidation secondary to drug treatment (e.g., rasburicase).¹¹ It may also be the result of various inherited or acquired diseases. Many medications can reduce uric acid levels in the blood either as their primary desired clinical effect (e.g., allopurinol) or as an unintended side effect (e.g., losartan).¹¹

While elevated blood uric acid levels are sufficient to diagnose hyperuricemia, clinical correlation via history and physical examination are required to make a definitive diagnosis of gout.¹² Other diseases related to uric acid require additional diagnostic testing.^13,14

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^8,15-18

Alcohol abuse
Decreased renal clearance
Renal failure
Hypothyroidism
Alcoholic ketoacidosis
Diabetic ketoacidosis
Diabetes insipidus
Hemolytic anemia
Tumor lysis syndrome
Rhabdomyolysis
Inherited disorders
- HGPRT deficiency (e.g., Lesch–Nyhan syndrome)
- PRPP synthetase superactivity
- Hereditary fructose intolerance
- Glycogen storage diseases (Types Ia, III, V, VII)
- Glucose-6-phosphate deficiency
- Down syndrome
Excessive consumption of purines
Myeloproliferative disorders
Lymphoproliferative disorders
Essential thrombocytosis
Hypoxemia
Drugs
- Loop diuretics
- Thiazide diuretics
- Cyclosporine
- Pyrazinamide
- Ethambutol

Low in:^6,9-11,19,20

Inflammation
Normal pregnancy
Total parenteral nutrition
Severe hepatocellular injury
Fanconi syndrome
Extracellular fluid expansion
- Excess intravenous fluid administration
- Primary polydipsia
- Syndrome of inappropriate antidiuretic hormone
Intracranial disease
Multiple sclerosis
AIDS
Malignancies (e.g., Hodgkin lymphoma)
Inherited disorders
- Hereditary xanthinuria
- Nucleosidase phosphorylase deficiency
- Familial renal hypouricemia
Drugs
- Aspirin
- Oral estrogens
- Ampicillin
- Calcium channel blockers
- Allopurinol
- Probenecid
- Febuxostat
- Enalapril
- Captopril
- Losartan
- Isoniazid
- Trimethoprim-sulfamethoxazole
- Rifampin
- Fenofibrate
- Atorvastatin
- Sulindac
- Rasburicase

FUNCTIONAL RANGE INDICATIONS:

High in:

Functional dysglycemia

Low in:

Deficiency of B12, folate, or molybdenum (these nutrients are cofactors for uric acid synthase; if MCV, MCH, and/or MCHC are elevated, this interpretation is more likely)

References: