Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form.[ Hyperuricemia may be the result of increased production of uric acid, decreased excretion of uric acid, or both increased production and reduced excretion.]
Signs and symptoms
Unless high blood levels of uric acid are determined in a clinical laboratory, hyperuricemia may not cause noticeable symptoms in most people.[ Development of gout which is a painful, short-term disorder is the most common consequence of hyperuricemia, which causes deposition of uric acid crystals usually in joints of the extremities, but may also induce formation of , another painful disorder.][
]
Causes
Many factors contribute to hyperuricemia, including genetics, insulin resistance, hypertension,
Causes of hyperuricemia can be classified into three functional types:
Increased production of uric acid
A purine-rich diet is a common but minor cause of hyperuricemia. Diet alone generally is not sufficient to cause hyperuricemia (see Gout). Foods high in the purines adenine and hypoxanthine may aggravate symptoms of hyperuricemia.
Various studies have found higher uric acid levels to be positively associated with consumption of meat and seafood and inversely associated with dairy food consumption.
Myogenic hyperuricemia, as a result of the Adenylate kinase reaction and the Purine Nucleotide Cycle running when ATP reservoirs in muscle cells are low (ADP>ATP), is a common pathophysiologic feature of glycogenoses such as GSD-III, GSD-V and GSD-VII, as they are metabolic myopathies which impair the ability of ATP (energy) production for the muscle cells to use.[Mineo I, Kono N, Hara N, Shimizu T, Yamada Y, Kawachi M, Kiyokawa H, Wang YL, Tarui S. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII. N Engl J Med. 1987 Jul 9;317(2):75-80. doi: 10.1056/NEJM198707093170203. PMID 3473284.] In these metabolic myopathies, myogenic hyperuricemia is exercise-induced; inosine, hypoxanthine and uric acid increase in plasma after exercise and decrease over hours with rest.
Hyperuricemia experienced as gout is a common complication of organ transplant.
Decreased excretion of uric acid
The principal drugs that contribute to hyperuricemia by decreased excretion are the primary . Other drugs and agents include , , pyrazinamide, ethambutol, nicotinic acid, ciclosporin, 2-ethylamino-1,3,4-thiadiazole, and .
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 .
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 of 1.92 (95% CI: 1.18-3.10) for renal dysfunction and 2.72 (95% CI: 1.64-4.52) for hyperuricemia.[Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. (2000 ), Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study; J Rheumatol. 2000 Jul; 27(7):1708–12 ( abstract).]
Mixed type
Causes of hyperuricemia that are of mixed type have a dual action, both increasing production and decreasing excretion of uric acid.
Pseudohypoxia (disrupted NADH/NAD+ ratio), caused by diabetic hyperglycemia and excessive alcohol consumption, results in hyperuricemia. The lactic acidosis inhibits uric acid secretion by the kidney, while the energy shortage from inhibited oxidative phosphorylation leads to increased production of uric acid due to increased turnover of adenosine nucleotides by the Adenylate kinase and purine nucleotide cycle.
High intake of alcohol (ethanol), a significant cause of hyperuricemia, has a dual action that is compounded by multiple mechanisms. Ethanol increases production of uric acid by increasing production of lactic acid, hence lactic acidosis. Ethanol also increases the plasma concentrations of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation, and is a possible weak inhibitor of xanthine dehydrogenase. As a byproduct of its fermentation process, beer additionally contributes purines. Ethanol decreases excretion of uric acid by promoting dehydration and (rarely) clinical ketoacidosis.
High dietary intake of fructose contributes significantly to hyperuricemia.
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 lacking in can induce extreme hyperuricemia; including some carbohydrate (and reducing the protein) reduces the level of hyperuricemia.
Gut microbiome
Radioisotope studies suggest about 1/3 of uric acid is removed in healthy people in their gut with this being roughly 2/3 in those with kidney disease.
Diagnosis
Hyperuricemia can be detected using blood and urine tests.
Treatment
Medications that aim to lower the uric acid concentration
used to treat hyperuricemia are divided into two categories: xanthine oxidase inhibitors and . For people who have recurring attacks of gout, one of these two categories of drugs is recommended.
Xanthine oxidase inhibitors
Xanthine oxidase inhibitors, including allopurinol, febuxostat and topiroxostat, decrease the production of uric acid, by interfering with xanthine oxidase.
Uricosurics
Uricosuric agents (benzbromarone, benziodarone, probenecid, lesinurad, sulfinpyrazone, ethebencid, zoxazolamine, and Tienilic acid) increase the excretion of uric acid, by reducing the reabsorption of uric acid once it has been filtered out of the blood by the kidneys.
Some of these medications are used as indicated, others are used Off-label use. In people receiving hemodialysis, sevelamer can significantly reduce serum uric acid,
Non-medication treatments for hyperuricemia include a low purine diet (see Gout) and a variety of dietary supplements. Treatment with lithium salts has been used as lithium improves uric acid solubility.
pH
Serum pH is neither safely nor 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 due to increased uric acid in the urine (see nephrolithiasis). Medications that have a similar effect include acetazolamide.
Temperature
Low temperature is a reported trigger of acute gout.
Prognosis
Increased levels predispose for gout and, if very high, kidney failure. Metabolic syndrome often presents with hyperuricemia.
See also
Further reading
External links
