View source for Hyperuricemia/ja

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| name            = Asymptomatic hyperuricemia
| image           = Harnsäure Ketoform.svg
| caption         = [[Uric acid/ja|尿酸]]
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'''高尿酸血症'''とは、[[blood/ja|血液]]中の[[uric acid/ja|尿酸]]が異常に高い状態である。体液のpH条件下では、尿酸は大部分が尿酸塩（イオン型）として存在する。血清尿酸濃度が女性で6&nbsp;mg/dL以上、男性で7&nbsp;mg/dL以上、青少年（18歳未満）で5.5&nbsp;mg/dL以上を高尿酸血症と定義する。体内の尿酸塩の量は、食物に含まれる[[purine/ja|プリン体]]の量、体内で合成される尿酸塩の量（[[cell turnover/ja|細胞のターンオーバー]]など）、および尿中または消化管から排泄される尿酸塩の量の間の[[homoeostasis/ja|バランス]]に依存する。高尿酸血症は、尿酸の産生増加、尿酸の排泄減少、または産生増加と排泄減少の両方の結果である。

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前高尿酸血症：
前高尿酸血症（pre-HU）は、血清尿酸値が男性で6-7&nbsp;mg/dL、女性で5-6&nbsp;mg/dlの間の高い正常値にある代謝状態として定義することができる。この値は現在、正常または高正常値と考えられている。このレベル、あるいはそれ以下でも、UAによる全身炎症が発症する。

==徴候と症状{{Anchor|Signs and symptoms}}==
高尿酸血症は、[[Medical laboratory/ja|臨床検査室]]で尿酸の高い血中濃度が測定されない限り、ほとんどの人に顕著な症状を引き起こさない。[[gout/ja|痛風]]を発症する。痛風の発症は高尿酸血症の最も一般的な結果であり、通常は四肢の関節に尿酸結晶が沈着するが、[[kidney stone/ja|腎臓結石]]の形成を誘発することもある。痛風の症状は、典型的には、強い痛みを伴う、足指や膝などの関節の[[inflammation/ja|炎症]]、腫れ、発赤である。高尿酸血症のすべての人が痛風を発症するわけではない。

==原因{{Anchor|Causes}}==
[[genetics/ja|遺伝]]、[[insulin resistance/ja|インスリン抵抗性]]、[[hypertension/ja|高血圧症]]、[[hypothyroidism/ja|甲状腺機能低下症]]、[[chronic kidney disease/ja|慢性腎臓病]]、[[obesity/ja|肥満]]、[[diet (nutrition)/ja|食事]]、[[iron overload/ja|鉄過剰症]]、[[diuretic/ja|利尿薬]]の使用（例、[[thiazide/ja|サイアザイド系]]、[[loop diuretic/ja|ループ利尿薬]]）、[[alcoholic beverages/ja|アルコール飲料]]の過剰摂取などである。これらのうち、アルコールの摂取が最も重要である。

高尿酸血症の原因は、尿酸産生亢進型、尿酸排泄低下型、混合型の3つの機能型に分類できる。産生亢進の原因としては、食事中の[[purine/ja|プリン体]]の量が多いこと、[[purine metabolism/ja|プリン体代謝]]が亢進していることなどが挙げられる。排泄低下の原因としては、腎臓病、ある種の薬物、尿酸と他の分子との排泄競争などがある。混合原因としては、食事中のアルコールおよび/または[[fructose/ja|フルクトース]]の高濃度、飢餓などがある。

===尿酸の産生が増加する===
{{Main/ja|Uric acid/ja#High uric acid}}

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A purine-rich diet is a common but minor cause of hyperuricemia. Diet alone generally is not sufficient to cause hyperuricemia (see [[Gout#Cause|Gout]]). Foods high in the purines [[adenine]] and [[hypoxanthine]] may aggravate symptoms of hyperuricemia.
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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.
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Myogenic hyperuricemia, as a result of the [[Adenylate kinase|myokinase (adenylate kinase)]] reaction and the [[Purine nucleotide cycle|Purine Nucleotide Cycle]] running when ATP reservoirs in muscle cells are low (ADP>ATP), is a common pathophysiologic feature of [[Glycogen storage disease|glycogenoses]] such as [[Glycogen storage disease type III|GSD-III]], [[Glycogen storage disease type V|GSD-V]] and [[Glycogen storage disease type VII|GSD-VII]], as they are [[Metabolic myopathy|metabolic myopathies]] which impair the ability of ATP (energy) production for the muscle cells to use. 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. Excess [[Adenosine monophosphate|AMP (adenosine monophosphate)]] is converted into uric acid. AMP → IMP → Inosine → Hypoxanthine → Xanthine → Uric Acid
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Hyperuricemia experienced as [[gout]] is a common complication of [[organ transplant|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.
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===Decreased excretion of uric acid===
{{Main|Uric acid#Low uric acid}}
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The principal drugs that contribute to hyperuricemia by decreased excretion are the primary [[antiuricosuric]]s. Other drugs and agents include [[diuretic]]s, [[salicylate]]s, [[pyrazinamide]], [[ethambutol]], [[nicotinic acid]], [[ciclosporin]], 2-ethylamino-1,3,4-thiadiazole, and [[cytotoxic agent]]s.
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The gene [[SLC2A9]] encodes a protein that helps to transport uric acid in the kidney. Several [[single nucleotide polymorphism]]s of this gene are known to have a significant correlation with blood uric acid. Hyperuricemia cosegregating with [[osteogenesis imperfecta]] has been shown to be associated with a mutation in [[GPATCH8]] using [[exome sequencing]]
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A [[ketogenic diet]] impairs the ability of the kidney to excrete uric acid, due to competition for transport between uric acid and [[ketone]]s.
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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 ratio]]s of 1.92 (95% CI: 1.18-3.10) for renal dysfunction and 2.72 (95% CI: 1.64-4.52) for hyperuricemia.
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===Mixed type===
Causes of hyperuricemia that are of mixed type have a dual action, both increasing production and decreasing excretion of uric acid.
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[[Pseudohypoxia]] (disrupted NADH/NAD<sup>+</sup> 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|myokinase reaction]] and [[purine nucleotide cycle]].
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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]].
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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 drink]]s 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 [[adenosine triphosphate|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.
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[[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 [[carbohydrate]]s 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.
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==Diagnosis==
Hyperuricemia can be detected using blood and urine tests.
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==Treatment==
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=== Medications that aim to lower the uric acid concentration ===
[[Medication]]s used to treat hyperuricemia are divided into two categories: [[xanthine oxidase inhibitor]]s and [[uricosuric]]s. For people who have recurring attacks of gout, one of these two categories of drugs is recommended. The evidence for people with asymptomatic hyperuricaemia to take these medications is not clear.
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==== Xanthine oxidase inhibitors ====
Xanthine oxidase inhibitors, including [[allopurinol]], [[febuxostat]] and [[topiroxostat]], decrease the production of uric acid, by interfering with [[xanthine oxidase]].
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==== Uricosurics ====
Uricosuric agents ([[benzbromarone]], [[benziodarone]], [[probenecid]], [[lesinurad]], [[sulfinpyrazone]], ethebencid, [[zoxazolamine]], and [[Tienilic acid|ticrynafen]]) 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.
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Some of these medications are used as [[Indication (medicine)|indicated]], others are used [[Off-label use|off-label]]. In people receiving [[hemodialysis]], [[sevelamer]] can significantly reduce serum uric acid, apparently by adsorbing urate in the gut. In women, use of [[combined oral contraceptive pill]]s is significantly associated with lower serum uric acid. Following [[Le Chatelier's principle]], lowering the blood concentration of uric acid may permit any existing crystals of uric acid to gradually dissolve into the blood, 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 [[Tophus|tophi]], then large 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. Precipitation of uric acid crystals, and conversely their dissolution, is known to be dependent on the concentration of uric acid in solution, [[pH]], sodium concentration, and temperature.
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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.
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===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]].
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===Temperature===
Low temperature is a reported trigger of acute gout. An example would be a day spent standing in cold water, followed by an attack of gout the next morning. This is believed to be due to temperature-dependent precipitation of uric acid crystals in tissues at below normal temperature.  Thus, one aim of prevention is to keep the hands and feet warm, and soaking in hot water may be therapeutic.
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==Prognosis==
Increased levels predispose for [[gout]] and, if very high, [[kidney failure]]. [[Metabolic syndrome]] often presents with hyperuricemia. Prognosis is good with regular consumption of [[allopurinol]] or [[febuxostat]].
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==See also==
* [[Hypouricemia]]
* [[Hyperuricosuria]]
* [[Metabolic myopathy|Metabolic myopathies]] (myogenic hyperuricemia)
* [[Purine nucleotide cycle]]
* [[Uric acid]]
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==Further reading==
* {{cite journal |vauthors=Nuki G, Simkin PA |title= A concise history of gout and hyperuricemia and their treatment |journal= [[Arthritis Research & Therapy]] |volume= 8 |issue= Suppl 1 |pages= S1 |year= 2006 |pmid= 16820040 |doi= 10.1186/ar1906 |pmc= 3226106 |doi-access= free }}
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== External links ==
{{Medical resources
|   ICD10          = {{ICD10|E|79|0|e|70}}
|   ICD9           = {{ICD9|790.6}}
|   ICDO           =
|   OMIM           =
|   MedlinePlus    =
|   eMedicineSubj  = med
|   eMedicineTopic = 1112
|   DiseasesDB     = 5375
|   MeshID         = D033461
}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mckd2  GeneReviews/NCBI/NIH/UW entry on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2]
* [https://www.ncbi.nlm.nih.gov/omim/162000,191845,603860,609886,162000,191845,603860,609886  OMIM entries on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy, Medullary Cystic Kidney Disease 2]
* [https://www.ncbi.nlm.nih.gov/books/NBK53700/  GeneReviews/NCBI/NIH/UW entry on Familial Juvenile Hyperuricemic Nephropathy Type 2]
* [https://www.ncbi.nlm.nih.gov/omim/179820,613092  OMIM entries on Familial Juvenile Hyperuricemic Nephropathy Type 2]
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{{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}}
{{Clinical biochemistry blood tests}}
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{{二次利用|date= 6 February 2024}}
[[Category:Uric acid]]
[[Category:Abnormal clinical and laboratory findings for blood]]
[[Category:Inborn errors of purine-pyrimidine metabolism]]
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