無症狀高尿酸血症

台灣痛風與高尿酸血症2016診治指引
參考資料 uptodate
治療
絕大多數無症狀高尿酸血症都不需要用藥治療, 要著重於飲食和生活習慣調整.
目前並沒有研究證實, 沒有症狀的高尿酸血症患者, 使用降尿酸藥物治療是否有好處.

We do not recommend pharmacologic management for the vast majority of patients with asymptomatic hyperuricemia, despite the high prevalence of this biochemical aberration.

持續性無症狀高尿酸血症患者 (> 8), 如果沒有證據顯示有尿酸結晶沉積, 應採用非藥物治療(生活作息調整) 降低尿酸, 衛教病患哪些情況可能需要服用降尿酸藥物.
All patients with persistent asymptomatic hyperuricemia (serum urate >8 mg/dL [480 micromol/L]) and without evidence of urate crystal deposition should be offered a plan for management with nonpharmacologic (lifestyle) measures to reduce the degree of hyperuricemia and educated with regard to the potential effects on urate levels of medical interventions for other conditions.

生活習慣調整, 與痛風的建議大多數相同, 包括將體重維持在理想體重, 調整食量, 食物組成, 避免飲酒, 避免添加糖的調味料, 規律運動, 但也要跟病患強調, 隨著新的醫學研究發表, 治療的適應症也會隨之調整.
The lifestyle interventions, largely overlapping those used for the prevention of gout, include reduction to ideal body weight by adjustment of dietary volume and composition, avoidance of alcohol and sugar-sweetened beverages, and regular exercise [7,74-76]. Mention should be made of the fact that treatment indications may change over time as new data are published. These interventions and evidence of their benefit are described in detail separately.

針對已有的疾病調整藥物, 盡量選擇可降低血中尿酸值的藥物, 或降低痛風發作的藥物, 避免會增加血中尿酸值的藥物
fenofibrate 可同時治療高血脂與降尿酸
Losacar (Losartan potassium) 是一種ARB
CCB

避免會增加血中尿酸濃度的藥物, 例如 thiazide 或 loop diuretics, ACEI. no-losartan的ARB, 以及 beta blocker.
When there are acceptable alternatives for the management of diseases accompanying hyperuricemia, we prefer the use of medications that reduce serum urate levels and/or decrease the risk for incident gout and the avoidance of medications/additives promoting hyperuricemia. Examples of the former include the use of fenofibrate for hyperlipidemia [77] and losartan [38,78] or calcium channel blockers [38] for hypertension. Likewise, agents that may promote hyperuricemia/incident gout that should be avoided, when possible, include thiazide or loop diuretics, angiotensin-converting enzyme (ACE) inhibitors, non-losartan angiotensin II receptor blockers, and beta blockers

對於無症狀病患, 對高正常值的患者, 或高尿酸血症的病患, 使用藥物降低尿酸是毫無根據的.
We consider pharmacologic urate-lowering therapy (with xanthine oxidase inhibitors or uricosuric agents) as generally unwarranted for upper normal range serum urate values or for asymptomatic hyperuricemia.

無症狀高尿酸血症患者, 如果影像檢查出現單鹽尿酸結晶沉澱, 處理策略與無症狀高尿酸血症相同, 不需因為影像檢查發現異狀而用藥治療. 但須告知病患影像檢查異常的含意, 與潛在的關聯
For persons with asymptomatic hyperuricemia in the presence of monosodium urate (MSU) crystal deposition (as by the finding of the double-contour sign or a suspected tophus) demonstrated only on imaging [49,50], we take the same approaches as for other asymptomatic individuals with hyperuricemia and do not view asymptomatic MSU crystal deposition detected on imaging alone as an indication for pharmacologic treatment, although patients should be advised of the finding and its potential implications.

高尿酸血症可能終身存在, 所以是否需要一輩子都吃藥, 要與病患討論用藥風險與不治療的風險
高尿酸血症可能會有哪些後果
終身服藥可能會有哪些好處或風險
治療可能會出現哪些罕見但致命的毒性反應, 例如吃 allopurinol 造成史帝芬強森症候群可能導致死亡. 例如秋水仙素的副作用和危險性

In the case of pharmacologic urate-lowering therapy, the estimated risk of clinical consequences from hyperuricemia should be weighed against the potential benefits and risks of lifelong drug treatment, since hyperuricemia often persists indefinitely. The risks of urate-lowering pharmacotherapy and associated treatments include rare but potentially severe and even life-threatening toxic reactions to agents such as allopurinol and colchicine

高尿酸血症或許不該看成一種疾病, 而是要當成可能造成尿酸結晶沉積的一種必要的先行條件
單鈉尿酸鹽(MSU)或尿酸結晶(不溶性尿酸)是高尿酸血症與臨床症狀(痛風發作,尿酸尿路結石, 痛風石產生)的必要病理生理關聯,
In the absence of unequivocal evidence for a causal role of this chemical aberration in one or more of the non-crystal deposition disorders associated with hyperuricemia (see 'Non-crystal deposition disorders' above), our view is that asymptomatic hyperuricemia is not a disease but can be regarded as a necessary (although not usually sufficient) predisposing factor for the narrow range of clinical manifestations of urate or uric acid crystal deposition. This view is supported by the fact that monosodium urate or uric acid crystal deposition, not soluble urate, is the essential pathophysiologic link between hyperuricemia and clinical manifestations such as gout flares, uric acid urolithiasis, and tophus formation

無臨床症狀高尿酸患者, 如果影像檢查有MSU結晶沉澱, 痛風發作的機率, 與高尿酸相關疾病的嚴重度, 目前沒有證據顯示有關聯
痛風發作是可治療的, 且可逆的,
預防性使用降尿酸藥物, 以避免尿酸結石疾病, 對多數人而言是不需要的
但若發現有結石, 應開始適當治療
尿酸尿路結石患者治療第一步是補充足夠水分(每天大於2000CC), 鹼化尿液 (吃草酸鉀或重碳酸鉀), 而不是吃 allopurinol. 
There is a lack of evidence regarding the outcomes of patients whose clinically asymptomatic hyperuricemia is accompanied by MSU crystal deposition demonstrated only by imaging with respect to incident gout or the range or severity of hyperuricemia-associated diseases. However, a gout flare is readily treatable and reversible if it occurs. Similarly, urate-lowering pharmacotherapy for prophylaxis against uric acid stone disease is not warranted in most individuals, but appropriate therapy should be started after discovery of a stone, as discussed elsewhere. The primary therapeutic modality in hyperuricemic but non-gouty individuals who experience a uric acid urinary tract stone is hydration (fluid intake >2 liters daily) and urinary alkalinization with potassium citrate or potassium bicarbonate, rather than allopurinol. The treatment of uric acid nephrolithiasis is discussed in detail separately.

尿酸要降到多低?
非痛風石的痛風患者, 如果尿酸相關的醫療狀況可能會導致尿路結石或阻塞性尿路病變, 建議將目標訂在 <6
沒有尿酸相關醫療狀況的高尿酸血症患者, 建議將目標控制在 < 8
As is the case in patients with non-tophaceous gout, the aim of urate-lowering therapy in patients with sustained marked but asymptomatic hyperuricemia and a urate-related medical condition very likely to result ultimately in recurrent urolithiasis and/or obstructive uropathy is serum urate <6 mg/dL (360 micromol/L). By contrast, in patients whose sustained asymptomatic hyperuricemia is unaccompanied by an identifiable urate-related medical condition likely to present such predictable renal risks, we suggest that a urate-lowering goal range <8 mg/dL (480 micromol/L) might suffice.

尿酸超過 8 以上應做檢查評估, 評估重點在於
- 痛風高風險族群, 或尿路結石需做降尿酸治療(有些降尿酸藥物會引起尿路結石)
- 服用可能導致高尿酸血症的藥物或接觸到毒物, 特別是有其他疾病(或高風險)的患者, 例如高血壓, 慢性腎病CKD, 缺血性心臟病, 這些病患可能不是尿酸上升導致疾病, 改變生活習慣或調整藥物可能有效
- 因其他潛在疾病或環境暴露導致尿酸上升,  可能需治療其他疾病
The aim of evaluating the cause of confirmed asymptomatic hyperuricemia is to identify the following:
●Patients at particularly high risk for gout or urolithiasis who warrant antihyperuricemic treatment.
●Hyperuricemia-inducing drugs or toxins that can be removed or substituted, with relief or diminution of the hyperuricemic state. This aim may be especially important in patients with or at high risk for disorders (such as hypertension, chronic kidney disease [CKD], and ischemic heart disease) which are commonly associated with hyperuricemia and for which lifestyle modifications and/or pharmacologic alternatives to hyperuricemia-inducing medications are usually available.
●Individuals whose hyperuricemia is a sign of an underlying disorder or environmental exposure requiring specific treatment.

尿酸 7-8 的病患應在 6-12 個月後追蹤尿酸是否超過 8 以上
第一次抽血檢查項目建議
CBC, DC
Cr, 電解質, Ca, 肝指數, 尿液分析

進一步檢查主要是根據懷疑的疾病針對性開立, 以確診或排除

Laboratory testing should include a complete blood count and differential leukocyte counts; a chemical profile, including measurement of renal function, electrolytes, calcium, and liver chemistries; and a urinalysis. Further laboratory determinations are directed to the specific causative factor suspected to confirm or deny the relationship.

病史需注意
其他疾病治療中的狀況
飲食
生活習慣
目前服用的藥物
是否暴露於毒素
是否有家族史
intercurrent medical conditions, diet or lifestyle choices, drug therapies, toxin exposure, or a known familial disorder

根據臨床經驗, 初步評估可能會找到一個以上, 會引起尿酸產生增加或腎臟排尿酸功能下降的成因
舉例, 兒童尿酸超過 10 以上, 或青少年超過 12, 要懷疑是否有淋巴過度增生或骨髓過度增生的疾病, 或未曾診斷的先天性心臟病, 先天性肺部疾病, 或先前有未診斷的遺傳性酵素缺陷導致尿酸製造過度
根據推測的成因安排影像檢查, 病理檢查, 基因檢查, 血液生化檢查
對於有多重成因的病患, 還要包括飲食或生活習慣的選擇, 是否服用其他可能影響尿酸平衡的藥物(例如loop diuretics)

In our experience, initial evaluation will identify one or more of the many causes of hyperuricemia due to increased urate production (table 1) or decreased renal uric acid clearance (table 2) in approximately 80 to 90 percent of patients. Modification or extension in the evaluation scheme is sometimes warranted by circumstances such as patient age and the extent to which the urate level exceeds normal. For example, marked hyperuricemia (exceeding 10 mg/dL [600 micromol/L] in a child) or 12 mg/dL [720 micromol/L] in an adolescent might prompt concern over an underlying lymphoproliferative or myeloproliferative state, a previously unappreciated congenital cardiac or pulmonary disorder, or a previously undiagnosed inherited enzyme defect resulting in urate overproduction. Such results would thus prompt appropriate imaging studies and/or pathologic, genetic, or biochemical measurements. Similarly, additional evaluation may be warranted among some patients with multiple possible explanations for their hyperuricemia, often including dietary or lifestyle choices or the use of medications affecting urate balance.

進一步評估
25歲以下男性患者, 或停經前婦女, 初步評估如果無法找出尿酸高的原因, 若腎功能正常, 可分析尿酸排出率, 這代表每一單位GFR會排出多少百分比的尿酸, 可鑑別尿酸製造過多或尿酸排出下降. 再據此找到高尿酸血症成因, 這也有助於降尿酸藥物選擇

Further evaluation — A determination of the fractional urinary excretion of uric acid (FEur), which represents the percent of urinary uric acid excretion per unit of the glomerular filtration rate (GFR), should be performed in both men presenting prior to age 25 and women prior to menopause who are without an identifiable cause of hyperuricemia on their initial evaluation and have stable and normal renal function; such testing can help to differentiate between causes resulting from overproduction of urate (table 1) and causes resulting from reduced uric acid clearance (table 2). The distinction between overproduction and underexcretion can guide further investigation of the underlying cause of hyperuricemia, and will be useful in directing the choice of antihyperuricemic medication in those needing treatment.
測量晨間尿液尿酸和肌酸酐, 血中尿酸和肌酸酐
FEur > 10 代表製造過多
FEur < 6 代表尿酸排出率下降

The FEur can be determined by measurement of the urate and creatinine concentration in a mid-morning spot urine collection and the serum urate and creatinine; this calculation will help to distinguish between urate overproduction with hyperuricosuria (FEur is usually >10 percent) and reduced urinary uric acid clearance (FEur is usually <6 percent) .

單次尿液檢驗計算 FEur, 與部分醫師所偏好的測量 24 小時的 尿酸排出, 其結果相似
如果每天尿液排出的尿酸超過 800mg, 或每公斤體重 12mg, 稱為高尿酸尿症
檢測時, 病患需採用標準飲食, 不可以喝酒, 避免吃影響尿酸代謝的藥,
The information gained by calculating the FEur using a spot urine is similar to that achieved by measurement of 24-hour urinary uric acid excretion, which, although a much more cumbersome procedure, is preferred by some investigators and clinicians. In this case, urinary uric acid excretion greater than 800 mg/day (4.8 mmol/day) or 12 mg/kg/day (71 micromol/kg per day) is defined as hyperuricosuria, while daily excretion below this level is indicative of reduced urinary uric acid clearance (with normal or reduced urinary uric acid excretion) [73]. The urine collections for these studies should be done while the individual is receiving a standard diet, excluding alcohol and drugs known to affect uric acid metabolism.

所謂的排出不足, 其實是排尿酸能力正常, 製造與排出平衡, 才會讓尿酸維持在穩定範圍
It is important to appreciate that "underexcretors" actually have a normal rate of urinary uric acid excretion since this is required to maintain the steady state in which production and clearance are relatively equal. It is the reduced efficiency of uric acid excretion that obligates a higher serum urate concentration to achieve a rate of urinary uric acid excretion that matches production. Similar considerations apply to diuretic therapy.

多數排尿酸不足的患者, GFR 是正常的, 沒有其他可證明的腎功能異常, 腎臟尿酸輸送缺陷(減少分泌或增加再吸收)可能是遺傳因素引起, 有一種以上的多態性 (風險基因) 尿酸輸送基因, 或後天(藥物或毒素引起), 或腎臟灌流下降引起(例如利尿劑).
Most patients with underexcretion of uric acid and with a normal GFR have no other demonstrable abnormality in renal function. The defect in renal urate transport (which could be manifested functionally either as reduced secretion or as enhanced reabsorption) may be inherited (often associated with one or more polymorphisms ["risk alleles"] in urate transporter genes); acquired (eg, related to a drug or toxin); or secondary to reduced renal perfusion (eg, diuretics).

Marked asymptomatic hyperuricosuria — 無症狀尿液高尿酸

高尿酸血症痛風病患, 如果每天排出尿酸超過 1100mg, 考慮治療, 以避免尿路結石
治療包括喝水每天 2000 cc 以上, 給予 allopurinol

無症狀高尿酸血症(沒有痛風), 如果合併每天尿酸排出超過 1100 mg (高尿酸尿症), 應先限制每天嘌呤攝取, 之後才考慮使用 allopurinol, 治療目標是將每天尿酸排出量減低至 1000mg 以下
In patients evaluated for sustained asymptomatic hyperuricemia who have urinary uric acid excretion in excess of 1100 mg (6.5 mmol) daily, we suggest treatment with interventions to reduce levels of urine uric acid. Based upon a reported 50 percent incidence of urolithiasis among the small proportion of gout patients with urinary uric acid excretion exceeding 1100 mg (6.5 mmol) daily [67], treatment with hydration (≥2 liters of fluids) and allopurinol has long been recommended for prevention or treatment of urinary tract stones in gouty individuals with this level hyperuricosuria [82] (see "Uric acid nephrolithiasis"). In patients with asymptomatic hyperuricemia and hyperuricosuria of similar degree, we believe that a trial of restricted dietary purine and purine precursor intake should precede initiation of allopurinol, with the aim of reducing daily renal urinary uric acid excretion to <1000 mg (6.0 mmol).


Failure to reach this goal or patient objection should lead to either of two robust alternatives for stone prophylaxis: first, hydration (>2 liters of fluids daily) and urinary alkalinization (goal: urinary pH ≥6.5 for at least several hours daily) (see "Uric acid nephrolithiasis"); or second, hydration and allopurinol. In the event urolithiasis occurs on the first regimen, substitution for potassium citrate by allopurinol, with reduction of serum urate levels (goal: <6 mg/dL) and urinary uric acid excretion (goal: <800 mg daily), can be done (see 'Evaluation' above and 'Initial evaluation' above and 'Further evaluation' above). The use of urate-lowering therapy can result in substantial reduction of stone risk among hyperuricosuric gout patients [82]; a comparable benefit of alkalinization appears the case in our experience and that of other experts, compared with historical experience