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Hyperuricemia
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Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L (6 mg/dL) for women and 400 µmol/L (6.8 mg/dL) for men.
es of hyperuricemia can be classified into three types: increased production of uric acid, decreased excretion of uric acid, and mixed type. Causes of increased production include high levels of purine in the diet and increased purine metabolism.
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Encyclopedia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L (6 mg/dL) for women and 400 µmol/L (6.8 mg/dL) for men.
Causes
Causes of hyperuricemia can be classified into three types: increased production of uric acid, decreased excretion of uric acid, and mixed type. Causes of increased production include high levels of purine in the diet and increased purine metabolism. Causes of decreased excretion include kidney disease, certain drugs, and competition for excretion between uric acid and other molecules. Mixed causes include high levels of fructose and/or alcohol in the diet, and starvation.
Increased production
A purine-rich diet is a common cause of hyperuricemia. Purine content of foods varies (see Gout). Foods high in the purines adenine and hypoxanthine may be more potent in exacerbating hyperuricemia.
Hyperuricemia of this type is a common complication of solid organ transplant. Apart from normal variation (with a genetic component), tumor lysis syndrome produces extreme levels of uric acid, mainly leading to renal failure. The Lesch-Nyhan syndrome is also associated with extremely high levels of uric acid.
Decreased excretion
The principal drugs that contribute to hyperuricemia of this type are the primary antiuricosurics. Other drugs and agents include alcohol (well known to have this property), diuretics, salicylates, pyrazinamide, ethambutol, nicotinic acid, cyclosporin, 2-ethylamino-1,3,4-thiadiazole, and cytotoxic agents.
The gene SLC2A9 encodes a protein that helps to transport uric acid in the kidney. Several single nucleotide polymorphisms of this gene are known to have a significant correlation with blood uric acid.
A ketogenic diet impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones.
Elevated blood lead is significantly correlated with both impaired kidney function and hyperuricemia (although the causal relationship among these correlations is not known). In a study of over 2500 people resident in Taiwan, a blood lead level exceeding 7.5 microg/dL (a small elevation) had odds ratios of 1.92 (95% CI: 1.18-3.10) for renal dysfunction and 2.72 (95% CI: 1.64-4.52) for hyperuricemia.
Mixed
Causes of hyperuricemia that are of "mixed" type have a dual action, both increasing production and decreasing excretion of uric acid.
High dietary intake of fructose contributes significantly to hyperuricemia. In a large study in the United States, consumption of four or more sugar-sweetened soft drinks per day gave an odds ratio of 1.82 for hyperuricemia. Increased production of uric acid is the result of interference, by a product of fructose metabolism, in purine metabolism. This interference has a dual action, both increasing the conversion of ATP to inosine and hence uric acid and increasing the synthesis of purine. Fructose also inhibits the excretion of uric acid, apparently by competing with uric acid for access to the transport protein SLC2A9. The effect of fructose in reducing excretion of uric acid is increased in people with a hereditary (genetic) predisposition toward hyperuricemia and/or gout.
Starvation causes the body to metabolize its own (purine-rich) tissues for energy. Thus, like a high purine diet, starvation increases the amount of purine converted to uric acid. A very low calorie diet without carbohydrate can induce extreme hyperuricemia; including some carbohydrate (and reducing the protein) reduces the level of hyperuricemia. Starvation also impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones.
Unclassified
Treatment
Precipitation of uric acid crystals, and conversely their dissolution, is known to be dependent on the concentration of uric acid in solution, pH, and temperature. Established treatments address these parameters.
The principal medications used to treat hyperuricemia act by decreasing the blood concentration of uric acid. These are xanthine oxidase inhibitors, which reduce the production of uric acid; and uricosurics, which reduce the reabsorption of uric acid excreted by the kidneys. Some of these medications are used as indicated, others are used off-label.
Following LeChatelier's principle, lowering the blood concentration of uric acid may permit any existing crystals of uric acid to be gradually dissolved into the blood, from whence the dissolved uric acid can be excreted. Maintaining a lower blood concentration of uric acid similarly should reduce the formation of new crystals. If the person has chronic gout or known tophi, then substantial quantities of uric acid crystals may have accumulated in joints and other tissues and aggressive and/or long duration use of medications may be needed.
Serum pH is neither safely or easily altered. Therapies that alter pH principally alter the pH of urine, to discourage a possible complication of uricosuric therapy: formation of uric acid kidney stones. Dietary supplements that can be used to make the urine more alkaline include sodium bicarbonate, potassium citrate, magnesium citrate, and Shohl's Solution (now replaced by Bicitra). Medications that have a similar effect include acetazolamide.
Non-medication treatments for hyperuricemia include a low purine diet (see Gout) and a variety of dietary supplements. These other treatments are regarded by many physicians as having little or no efficacy.
Other medications
Several medications other than xanthine oxidase inhibitors and uricosurics can (or are suspected to) lower serum uric acid. These include:
Research
Experimental compounds known to lower serum uric acid include:
Prognosis
Increased levels predispose for gout and, if very high, renal failure. The metabolic syndrome often presents with hyperuricemia.
Persons with gout, and by inference hyperuricemia, are significantly less likely to develop Parkinson's disease, unless they also require diuretics.
Dalmatian dogs
In Dalmatian dogs, a lack of uricase (a genetic trait fixed in this breed) contributes to hyperuricemia and corresponding hyperuricosuria.
History
Hyperuricemia has a very long history in medicine.
See also
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