痛風與高尿酸血症最新發展與整體回顧

Gout and hyperurecemia: recent advances and a systematic review

痛風是一個增加中的常見風濕疾病，各國研究發現一般群眾過去四十年的血中尿酸平均值升高。此外近年來認為高尿酸血症是心臟血管疾病的獨立及可改變危險因子，也又引發高度興趣。本文討論痛風與高尿酸血症在流行病學、病理機轉、臨床表現及治療方面的最新進展與回顧。人類尿酸氧化酶（Uricase）因演化上突變而失去功能，加上腎小管尿酸的有效再吸收，因此造成人的血中尿酸值比其他種生物高，其真正原因至今雖然仍不甚明白，但從演化觀點而言應有其生物學上的意義。必需指出許多痛風患者至令尚未接受良好的控制，更強調痛風和高尿酸血症造成社會負擔。最近在腎小管尿酸排泄分子機轉的研究了解，提供未來研發更好的促進尿酸排泄藥物基礎。雖然至令仍未確定高尿酸血症是否為心臟血管疾病的獨立危險因子，一旦確立血中尿酸過高時，應立即尋找相關的心臟血管疾病危險因子是否也存在。如果未來研究資料支持治療無症狀高尿酸血症來預防心臟血管疾病，則我們治療無症狀高尿酸血症的思維將大大改變。由實證觀點來看，目前痛風的治療包括長期使用降尿酸藥物，都是建立在過去經驗上，例如長期使用Allopurinol或Uricosuric agent預防痛風發作，兩者對腎功能的影響及其相對安全性仍然未明朗，且需要有隨機分配對照控制的良好研究，才能明白其間的差異。

Gout is an increasingly common rheumatic disease. Global studies have found an increase in mean serum urate in both genders during the past four decades. Furthermore, there has been a resurgence of interest in hyperuricemia as an independent and potential modifiable cardiovascular risk factor. This work discusses recent advances in the epidemiology, pathogenesis, clinical manifestations, and treatment of gout and hyperuricemia. Humans have an uricase silencing mutation together with effective renal tubule urate reabsorption, thus resulted in a high urate levels. From evolutionary point of view, hyperuricemia should be biologically relevant. However, the exact role of uric acid as an end product of purine metabolism in human remains unclear. It is important to point out that many gout patients are not been adequately managed and highlighting the burden of gout and hyperuricemia. Recent advances in understanding of the molecular mechanisms of renal urate handling may help in developing better uricosuric agents in the future. Though it remains uncertain whether hyperuricemia is an independent risk factor for cardiovascular disease, a diagnosis of hyperuricemia or gout should prompt a search for cardiovascular risk factors. If data supporting treatment of hyperuricemia to prevent cardiovascular or renal disease become available in the future, such data will significantly change the way we treat asymptomatic hyperuricemia. However, well-designed randomized controlled study is necessary to clarify this. From evidence-based point of view, the current treatment practices of patients with gout, including long-term prevention of gout recurrence, are largely empirical. For example, the long-term effect of allopurinol or uricosuric agents on renal function and their relative safety is still unknown and requires examination via a well designed, randomized controlled study.