研究目的: 痛風無論在任何一個國家或地區皆是很常見的疾病。傳統上，痛風的病人被認為有較高的風險將來會發生慢性腎臟病；這樣的印象也使本來沒有腎臟病的痛風的病人擔心害怕將來會有慢性腎臟病。在過去，尿調理素排出量和慢性腎臟病之間的關係在醫學上無論臨床或基礎研究，已有相當多的臨床研究成果。尤其，許多研究顯示，尿調理素排出量在影響慢性腎臟病腎臟功能是否繼續變差，扮演著重要角色。但是有關尿調理素排出量和痛風及非痛風病人合併慢性腎臟病的相關性還不是很清楚。
研究方法:我們執行一個以醫院腎臟科及風溼科自2011年6月1日到2012年12月10日期間，以醫院腎臟科及風溼科為主，共完成收集72個經風溼科診斷確認的痛風病人，及腎臟科、風溼科共收案的42個非痛風病人的血清及尿液檢體。全部114個受試者依據腎絲球過濾率分成兩組:慢性腎臟病(腎絲球過濾率＜60 ml/min per 1.73m2)及非慢性腎臟病。兩組性別、年齡、血清生化值及尿液生化值尿調理素皆記錄及分析。尿液中尿調理素排出量是依尿調理素/尿肌酸酐比例來計算。
研究結果：由統計分析結果得知，痛風受試者尿調理素排出量和腎絲球過濾率有顯著的正相關。非痛風病人，尿調理素排出量和腎絲球過濾率則沒有相關。在慢性腎臟病及非慢性腎臟病兩組的比較中；性別、高血壓、糖尿病及是否被診斷有痛風，兩組並無差異。然而年齡 (慢性腎臟病組: 62.2 ± 13.8, 非慢性腎臟病組: 43.9 ± 12.8, p<0.0001)、血清尿酸值(慢性腎臟病組: 8.2 ± 2.2毫克/分升, 非慢性腎臟病組: 7.20 ± 1.73毫克/分升, p<0.05)在兩組的比較中，具有顯著的差異。尿調理素排出量(慢性腎臟病組:3.7±4.8,非慢性腎臟病組:5.8±6.1,p<0.05)在慢性腎臟病及非慢性腎臟病兩組的比較中，兩組同樣有顯著的差異。多變項的分析模式中，具慢性腎臟病且有痛風的病人比只有痛風而無慢性腎臟病的病人，有較低尿調理素排出量。[勝算比: 0.796, 95%信賴區間: 0.665-0.934, p =0.006)。此外慢性腎臟病和痛風的病人在本研究中比較，有痛風病人年齡大 (p<0.001) 且有較高的血清尿酸值(p<0.05) 。而在非痛風病人尿調理素分泌量和慢性腎臟病沒有相關性。
研究結論：本研究讓我們推論，尿調理素在痛風病人是否會慢性腎臟病極可能扮演非常重要的角色。未來的研究期待能建立尿調理素在痛風及慢性腎臟病動物模式，探究其病理生理機轉，也許未來，尿調理素在痛風病人慢性腎臟病的治療與臨床上可以有很多的應用。

INTRODUCTION AND AIMS: Gout is a popular disease worldwide. Traditionally, patients suffering from gout were thought to be at high risk for renal complications and people who had gout always worry about the potential risks of getting a kidney disease. The link between uromodulin (UMOD) and chronic kidney disease (CKD) has attracted much interests in the medical literature and several investigations showed UMOD had active role in CKD progression. To our knowledge, the association of urinary UMOD excretion on gout and non-gout patients with CKD has not been thoroughly investigated.
METHODS: A total of 114 Taiwanese patients with stable disease activity selected from a cohort that attended our renal and rheumatology outpatient department were enrolled (Non-Gout patients: 40 ,Gout patients: 74) between Jun. 1, 2011 and Dec. 13, 2012. Patients were divided into CKD group (N=68) and non-CKD (N=46) group. CKD was defined by MDRD equation estimate glomerular filtration rate (eGFR)＜60 ml/min per 1.73m2. Their demographic data, laboratory tests including serum creatinine, serum uric acid eGFR, and urinary creatinine and UMOD level were measured. Urinary UMOD excretion was calculated as UMOD/UCR ratio.
RESULTS: Using Pearson correlation analysis, urinary UMOD excretion correlated positively with eGFR in patients with Gout. In non-gout patients, urinary UMOD excretion does not correlate with eGFR. Gender, status of DM, gout and hypertension do not show significant difference between CKD group and non-CKD group. However, age (CKD group: 62.2 ± 13.8, Non-CKD group: 43.9 ± 12.8, p < 0.0001) and serum uric acid (CKD group: 8.2 ± 2.2 mg/dl, Non-CKD group: 7.2 ± 1.7 mg/dl, p <0.05) are significantly different between CKD group and non-CKD group. Urinary UMOD excretion is also statistical significantly between two groups (CKD group: 3.7± 4.8, Non-CKD group: 5.8 ± 6.1, p <0.05). Using multivariate analysis, patients with CKD and gout were associated with lower urinary UMOD excretion than those who have gout alone [Odds Ratio 0.796, 95% confidence interval: 0.665-0.934, p=0.006). Patients with CKD and gout were also more likely to be older (p < 0.001) and have higher uric acid levels (p < 0.05). In non-gout patient, urinary UMOD excretion was not associated with status of CKD instead.
CONCLUSIONS:
Our study indicates that UMOD might play a role in the relationship between gout and CKD. Further studies with animal model of gout and CKD are mandatory to establish fundamental pathomechanism and explore the clinical implications.

目錄
論文審定書…………………………………………….i
誌謝…………………................……………………… ii
中文摘要……………………………………….………iii
英文摘要…………………………..………………...... v
前言…………………………………………………... 1
什麼是慢性腎臟病 …………………………………...3
台灣的慢性腎臟病流行病學…...…………………….5
高尿酸血症、痛風與慢性腎臟病流行病學………….6
痛風及非痛風病人尿液中尿調理素排出量和慢性腎臟病的相關性探討
研究背景及目標 …………………………………………………….…..…7
材料方法……………………………………………………….10
結果………………........................…………………….14
討論………………........................…………………….16
未來研究與展望 ………………………………………………………….19
參考文獻……………………………………………….20
圖1:尿調理素是位於腎臟腎臟亨利氏環上行支細胞所分泌………………23
圖2:Uromodulin基因存在的染色體位置…………………………………………24
圖3:文獻上已發表 Uromodulin基因突變位置…………………………………25
圖4:在痛風病人，尿調理素排出量和估算腎絲球過濾率的相關性…….. 27
圖5:在非痛風病人，尿調理素排出量和估算成人腎絲球過濾率的相關性…………………………………………… 28
圖6:尿調理素排出量和血清尿酸值的相關性…………………29
表1:美國腎臟基金會對慢性腎臟疾病的分期………………………………30
表2:慢性腎臟病和非慢性腎臟病病人各類別及連續變項間的相關性…… 31
表3:尿調理素排出量和估算腎絲球過濾率在痛風病人與非痛風病人的相關性 ………………………………….32
表4: 以逐步迴歸選取法來分析痛風病人與非痛風病人各個變量和慢性腎臟病的關係…………………………..33

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