Many factors contribute to<unk> , including genetics, insulin resistance, hypertension, hypothyroidism, chronic kidney disease, obesity, diet, iron overload, use of diuretics (e.g. thiazides, loop diuretics), and excessive consumption of alcoholic beverages. Of these, alcohol consumption is the most important. Causes of<unk>  can be classified into three functional 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 alcohol and/or fructose in the diet, and starvation. Increased production of uric acid A purine-rich diet is a common but minor cause of<unk> . Diet alone generally is not sufficient to cause<unk>  (see Gout). Foods high in the purines adenine and hypoxanthine may aggravate symptoms of<unk> . 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.<unk>  experienced as gout 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 kidney failure. The Lesch–Nyhan syndrome is also associated with extremely high levels of uric acid. Decreased excretion of uric acid The principal drugs that contribute to<unk>  by decreased excretion are the primary antiuricosurics. Other drugs and agents include diuretics, salicylates, pyrazinamide, ethambutol, nicotinic acid, ciclosporin, 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.<unk>  cosegregating with osteogenesis imperfecta has been shown to be associated with a mutation in GPATCH8 using exome sequencing 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<unk>  (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<unk> . Mixed type Causes of<unk>  that are of mixed type have a dual action, both increasing production and decreasing excretion of uric acid. High intake of alcohol (ethanol), a significant cause of<unk> , 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<unk> . 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<unk> . 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<unk>  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 lacking in carbohydrates can induce extreme<unk> ; including some carbohydrate (and reducing the protein) reduces the level of<unk> . Starvation also impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and ketones.
Hyperuricemia
Metabolic syndrome
Azotemia
Anuria
Crystalluria
Hypercalciuria
Uremia
Oliguria