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研究生:王姿文
研究生(外文):Wang, Tzu-Wen
論文名稱:腎素抑制劑在高血壓慢性腎疾病患者對蛋白尿及腎功能的影響之回溯性分析
論文名稱(外文):A Retrospective Study To Evaluate The Effect Of Renin Inhibitor On Patients With Hypertension And Chronic Kidney Disease(CKD)
指導教授:藍守仁藍守仁引用關係
指導教授(外文):Lan, Shou-Ren
口試委員:林柏松謝嫣娉藍守仁
口試委員(外文):Lin, Bo-SongXie, Yan-PingLan, Shou-Ren
口試日期:2012-06-20
學位類別:碩士
校院名稱:亞洲大學
系所名稱:健康產業管理學系健康管理組碩士在職專班
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:59
中文關鍵詞:腎素抑制劑高血壓蛋白尿
外文關鍵詞:direct rennin inhibitorshypertensionproteinuria
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背景與目的:高血壓與蛋白尿是腎功能惡化的危險因子。藉由血管收縮素轉化酶抑制劑與第二血管收縮素第一型接受器阻斷劑來抑制腎素血管收縮素系統(RAAS),對於治療高血壓、糖尿病腎病變等疾病已經被證實為一種有效的方法。腎素是催化RAAS的第一步驟,新一代的降血壓藥物-直接腎素抑制劑,作用於腎素血管收縮素系統的活化點上,於2008年取得台灣衛生署許可證後,尚缺乏國人臨床使用經驗的研究報告。本研究主要目的為探討腎素抑制劑在高血壓患者,降血壓之療效與蛋白尿及腎功能的影響情形,在高血壓合併糖尿病與非糖尿病患者,及腎功能eGFR<60ml/min/1.73m2與eGFR>60ml/min/1.73m2患者,對於降血壓之療效、與腎功能的影響是否有差異。次要目的為分析血清鉀離子與血清肌酸酐濃度的變化,是否有上升的安全性疑慮。

研究方法:本研究為回溯性病歷資料分析,以中區某區域醫院為例,搜集自2010年4月至2011年10月,接受直接腎素抑制劑Aliskiren治療三個月之所有具高血壓診斷之年滿18歲患者,使用t檢定來進行分析。

研究結果:本研究共取得219名使用Aliskiren之高血壓患者資料,合併糖尿病患者占50%,使用Aliskiren三個月收縮壓降8.1mmHg、舒張壓降4.3mmHg,且降低蛋白尿UACR(Urine Albumin to Creatinine Ratio, UACR)202.2mg/g均達統計學上顯著差異。在糖尿病組的腎絲球濾過率eGFR增加3.3 ml/min/1.73m2、非糖尿病組下降4.4 ml/min/1.73m2。在腎功能較差的患者eGFR增加了2.1 ml/min/1.73m2、腎功能較好的反而下降了5.7 ml/min/1.73m2,不同的病患族群其腎功能的變化結果不同。血清鉀離子變化均未達統計學上顯著差異。

結論與建議:本研究結果顯示,Aliskiren介入不同的病患族群,同樣降低血壓及蛋白尿的情況之下,腎功能eGFR的變化卻有所不同,非糖尿病及腎功能較好的病患腎功能eGFR有下降的趨勢,建議醫師於臨床使用Aliskiren時,應監測多項指標來評估腎功能的變化,目前的研究大多僅以替代指標(蛋白尿)來評估,並建議未來的研究還需要設立較嚴格的腎功能指標來評估腎臟保護作用。

Background: Proteinuria and hypertension are both important risk factors for progression of renal diseases. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are RAAS(Renin-Angiotensin-Aldosterone-System) blockade agents which have been shown to be effective therapeutic approaches for controlling of hypertension and prevention of renal damages in patients with hypertension. In the rate-limiting step of the RAAS cascade, renin is the main determinant of RAAS activity and has been considered the optimal target for RAAS suppression. Aliskiren is the first-in-class direct rennin inhibitor as oral antihypertensive agents which was approved in 2008 for the treatment of hypertension in Taiwan, however, clinical data in Taiwanese population is still lacking after launch in Taiwan. The major objective of our study is to compare the blood pressure lowering efficacy, anti-proteinuria potential, and the effect on renal function by renin inhibition in hypertensive patients, with and without diabetes, and in subgroups with eGFR<60ml/min/1.73m2 and with eGFR>60ml/min/1.73m2. The secondary objective is to assess changes of serum potassium and serum creatinine concentration in various subgroups from safety perspectives.

Methods: This study is a retrospective analysis which collect clinical data of adult patients(above 18 year-old) who were diagnosed with hypertension and accepted direct renin inhibitor, alikiren treatment for at least three months from April 2010 to October 2011 in Central of regional hospital, using the t test statistical method.

Results: Clinical data of a total of 219 adults from April 2010 to October 2011 were analyzed in this retrospective study, and among all the patients 50% of them were diagnosed with diabetes mellitus. Patients treated with Aliskiren for 3 months showed 8.1 mmHg (p<0.001) decrease of systolic blood pressure, and 4.3mmHg (p<0.001) decrease of diastolic blood pressure. The average reduction of UACR (urine serum albumin-creatinine ratio) was 202.2mg / g (p=0.034) which is statistically significant. The results showed 3.3 ml/min/1.73m2 increase of GFR in diabetic patients but 4.4 ml/min/1.73m2 (p=0.002) decrease in non-diabetic patients. In subgroups with various GFR, the results also showed 2.1 ml/min/1.73m2 increase of GFR in patient subset with eGFR<60ml/min/1.73m2, and 5.7 ml/min/1.73m2 decrease of GFR in patient subset with eGFR>60ml/min/1.73m2 (p=0.031). No significant changes of serum potassium were observed in this analysis.

Conclusions: The results of this study showed that with the blood pressure lowering efficacy and anti-proteinuria potential, Aliskiren may result in different effects on renal function in various patient populations. The decline of eGFR in hypertensive patient subgroups with non-diabetic group or with renal function eGFR> 60ml/min/1.73m2 suggested that the physicians should monitor a number of indicators to assess changes of renal function while patient with hypertension are treated with Aliskiren. The present study only assessed surrogate marker of proteinuria, UACR, and suggested that further studies to establish more stringent evaluation of renal function and renal protection effect are still necessary.

中文摘要
英文摘要
目錄i
表目錄ii
圖目錄iii
第一章 緒論
第一節 研究背景與動機 1
第二節 研究目的 4
第二章 文獻探討
第一節 腎素-血管收縮素醛固酮系統 6
第二節 高血壓的治療目標 17
第三節 慢性腎疾病與高血壓的關聯 19
第三章 研究方法
第一節 研究架構 23
第二節 研究對象、資料來源及測量變項 26
第三節 分析方法 32
第四章 研究結果
第一節 分析樣本在Aliskiren介入前後的差異 33
第二節 比較糖尿病組與非糖尿病組在Aliskiren介入前後變化的差異 37
第三節 比較腎功能較好組與腎功能較差組在Aliskiren介入前後變化的差異 43
第五章 討論與研究限制
第一節 研究結果的討論 49
第二節 研究限制 52
第六章 結論與建議
第一節 結論 53
第二節 建議 54

參考文獻 55

表 目 錄
表 2-1 ACEIs、ARBs、DRIs不同機轉阻斷RAAS路徑,其PRA表現不同 8
表 2-2 ARBs對糖尿病合併有腎病變患者之臨床研究成果 15
表 2-3 ACEIs對糖尿病與非糖尿病合併有腎病變患者之臨床研究成果 16
表 2-4高血壓治療指引 17
表 2-5美國國家腎臟基金會對慢性腎疾病的分期 20
表 3-1變項說明表 30
表 3-1變項說明表(續) 31
表 4-1 樣本的描述性統計 34
表 4-1 樣本的描述性統計(續) 35
表 4-2 Aliskiren介入三個月各變項降幅差異-配對樣本t檢定 36
表 4-3 糖尿病組與非糖尿病組的樣本的敘述性統計 40
表 4-3 糖尿病組與非糖尿病組的樣本的敘述性統計(續) 41
表 4-4 各變項降幅差異-以有無糖尿病區分 42
表 4-5 腎功能較好組與腎功能較差組的樣本的敘述性統計 46
表 4-5 腎功能較好組與腎功能較差組的樣本的敘述性統計 47
表 4-6 各變項降幅差異-以腎功能較好組與腎功能較差組區分 48

圖 目 錄
圖2-1 腎素-血管收縮素醛固酮系統,ACEIs與ARBs會造成傳達負向回饋訊息消失圖 7
圖3-1 研究架構 23
圖3-2 資料來源流程圖 29


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