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研究生： 林婉婷
Lin, Wan-Ting
論文名稱： 腎絲球腎炎之藥物治療
Pharmacotherapy in Glomerulonephritis
指導教授： 高淑敏
Kao, Shu-Min
黃建鐘
Huang, Chien-Chung
高雅慧
Kao, Ya-Hui
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床藥學研究所
Institute of Clinical Pharmacy
論文出版年： 2003
畢業學年度： 91
語文別： 中文
論文頁數： 155
中文關鍵詞： 菌酚嗎碄乙基酯 、每日尿蛋白流失量 、腎絲球腎炎 、類固醇
外文關鍵詞： glomerulonephritis, glucocorsteroids, mycophenolate mofetil, daily protein loss
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    • 腎絲球腎炎 (Glomerulonephritis, GN) 是造成末期腎病 (end-stage renal disease，ESRD) 的主要原因之一；若早期給予藥物治療，能保留腎功能和減少腎衰竭的發生。目前治療腎絲球腎炎的藥物中，以類固醇 (steroids) 為第一線用藥物；若是治療失敗或容易復發時，可併用其他免疫抑制劑 (immunosuppressants) 作治療，因其具有細胞毒性和引發各種副作用，會造成治療之困難；Mycophenolate mofetil (MMF) 是一新的免疫抑制劑，先應用於腎移植，近年來陸續用來治療器官移植以外疾病，包括：腎絲球腎炎和自體免疫疾病。本研究的主要目的是經由回溯性觀察方式，從2002年10月至2003年4月，分析成大醫院十七位GN患者對MMF治療之反應。他們曾接受過三個月以上MMF之治療且對類固醇有依賴性 (十位) 或抗性 (兩位)，曾使用其他免疫抑制劑治療，但反應不佳或復發者有五位。腎臟切片的病理診斷，有七位為膜性腎病變 (membranous nephropathy, MN)，五位為微細病變 (minimal change disease, MCD)，以及五位其他組，包括：甲型免疫球蛋白腎病變 (IgA nephropathy) 一位，局部節段性腎絲球硬化 (focal segmental glomerulosclerosis, FSGS) 兩位和狼瘡性腎炎 (lupus nephritis) 兩位。男女的比例為9: 8，平均年齡為40.9 �b 14.3 歲。主要評估GN患者接受MMF治療前後的每日尿蛋白流失量 (daily protein loss, DPL) 和血清肌酸酐 (serum creatinine, SCr) 之變化，以中位數 (範圍) 來表示。另外，也評估患者在MMF治療前後的肌酸酐廓清率 (creatinine clearance, CrCl)、血清白蛋白和膽固醇濃度之變化，並觀察MMF治療期間的副作用以及類固醇、ACEI或AIIA和HMG CoA 還原酶抑制劑 (statins) 的併用情形。
    MMF治療劑量與療程之中位數 (範圍) 分別為每天1 (0.5-1) 克的和治療14 (3-49) 個月，發現GN患者的DPL在MMF治療前為4.8 (1.7-15) 公克，治療後明顯降低為2.3 (0.3-14.1) 公克 (p = 0.009)；治療前後的SCr，則無顯著差異 (1.0 mg/dL vs. 1.0 mg/dL , p > 0.05)，而CrCl、血清白蛋白和膽固醇濃度在治療前後的變化，也沒有差異性。其中膜性腎病變的患者對MMF治療的反應最好，DPL由治療前的每天4.8 (1.8-8.6) 公克降低至治療後每天0.4 (0.3-2.3) 公克 (p = 0.018)，血清白蛋白由3.3 mg/dL 增加至3.8 mg/dL (p = 0.042)，膽固醇由290 mg/dL降低至213 mg/dL (p = 0.028)。MCD患者在MMF治療前後的DPL、SCr、CrCl、血清白蛋白和膽固醇濃度，都不具有顯著差異 (p > 0.05)；至於合併FSGS、IgAN和LN患者之「其他組」，接受MMF治療後，DPL由4.8公克下降至3.4公克(p = 0.043)。安全性方面，對MMF的耐受性良好，未出現嚴重的胃腸或白血球降低的副作用。由單變項分析發現，膜性腎病變患者接受MMF治療容易降低其DPL；多變項分析中，併用ACEI/AIIA、未使用過免疫抑制劑治療以及膜性腎病變患者，接受MMF治療容易降低其DPL。
    因此，MMF治療對類固醇或其他免疫抑制劑反應不佳的GN患者，可有效地降低DPL，且穩定腎功能。而膜性腎病變患者，除降低DPL，也會改善血中白蛋白和膽固醇值。但微細病變患者接受MMF治療後未有明顯之反應，可考慮提高MMF的治療劑量或以其他免疫抑制劑（如：Cyclosporine）作治療。「其他組」的DPL，呈現有意義下降。未來可增加病人數或作前瞻性的GN研究，以評估MMF之確切療效。

    Glomerulonephritis (GN) is a major cause of end-stage renal disease (ESRD). Glucocorsteroids alone or in combination with cytotoxic agents or cyclosporine have been used to treat GN patients with unsuccessful response or having potential toxicities. Mycophenolate mofetil (MMF) is an immunosuppressive agent widely used in transplant recipients. We retrospectively evaluated the effectiveness of MMF as the empirical treatment for refractory GN in Division of Nephrology, National Cheng Kung University Hospital, Tainan, Taiwan.
    From October 2002 to April 2003, 17 GN patients with poor response or relapse after steroids or cytotoxic agents had received MMF therapy at least 3 months were enrolled into study. The pathologic findings were grouped into membranous nephropathy (MN, N = 7), minimal change disease (MCD, N = 5), and the other group including: focal segmental glomerulosclerosis (FSGS, N = 2), IgA nephropathy (IgAN, N = 1) and lupus nephritis (LN, N = 2). The median (range) of daily protein loss (DPL), serum creatinine, creatinine clearance, serum albumin and serum cholesterol at the start and the end of MMF therapy were compared using the Wilcoxon signed-ranks test. The use of steroid, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonist (AIIA), and 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) was also analyzed.
    The median (range) dose and duration of MMF therapy in these GN patients were 1 (0.5-1.0) g/day and 14 (3.0-14.0) months. The results showed that DPL decreased from 4.8 (1.7g - 15.0) g to 2.3 (0.3- 14.1; p < 0.05) g, but there was no significant change of serum creatinine (1.0 mg/dL vs. 1.0 mg/dL, p > 0.05), creatinine clearance (67.3 mg/dL vs. 78.0 mg/dL, p > 0.05), serum albumin (3.3 mg/dL vs. 3.8 mg/dL, p > 0.05), or serum cholesterol (290.0 mg/dL vs. 224.0 mg/dL, p > 0.05) in all GN patients at the end of MMF therapy. MN patients had better improvement of DPL (4.8 g decreased to 0.8 g, p = 0.018), serum albumin (3.3 g increased to 3.8 g, p = 0.042), and cholesterol (290.0 mg/dL decreased to 213.0 mg/dL, p = 0.028) than other patients at the end of MMF therapy. But MCD patients showed no significant difference of DPL, serum creatinine, creatinine clearance, serum albumin, or serum cholesterol at the end of therapy. The other group only had significant improvement of DPL at the end of therapy (4.8 g vs. 3.4 g, p = 0.043). Side effects of MMF were uncommon and generally mild. In multivavariate analysis,
    decrease of DPL correlated with the concomitant use of ACEI/AIIA, no previous treatment of cytocoxic agents and MN patients.
    In brief, MMF therapy for patients with refractory GN was well tolerated and can improve DPL and preserve the renal function.

    中文摘要…………………………………………………………………...I 英文摘要…………………………………………………………………...IV 致謝………………………………………………………………………...VI 縮寫………………………………………………………………………...VII 目錄………………………………………………………………………...VIII 表目錄……………………………………………………………………...XIV 圖目錄……………………………………………………………………...XVI 第一篇 腎絲球腎炎的藥物治療………………………………………….1 第壹章 研究背景………………………………………………………….1 第貳章 文獻回顧………………………………………………………….2 第一節 腎絲球腎炎…………………………………………………….2 1.1 定義………………………………………………………………2 1.2 分類………………………………………………………………2 第二節 致病機轉……………………………………………………….4 第三節 臨床表徵……………………………………………………….6 第四節 評估與診斷…………………………………………………….7 第五節 藥物治療……………………………………………………….10 5.1 膜性腎病變(Membranous nephropathy, MN)的藥物治療……...13 5.1.1 類固醇單ㄧ療法…………………………………………….13 5.1.2.免疫抑制劑療法……..………………………………………16 5.1.2.1 Azathioprine (AZA)……………………………………...16 5.1.2.2 烷基化劑 (alkylating agents)…………………………...16 5.1.2.3 Cyclosporin (CsA)………………………………………..20 5.1.3 結論……………………………..……………………………20 5.2 微細腎病變 (Minimal change disease) MCD的藥物治療……...21 5.2.1 類固醇………………………………………………………...21 5.2.1.1 首次發作的治療…………………………………………21 5.2.1.2 復發性MCD的治療…………………………………….22 5.2.2 免疫調節劑 (Immunmodulator agents)……………………...23 5.2.2.1 Cyclophosphamide (CYC)………………………………..24 5.2.2.2 Chlorambucil……………………………………………...24 5.2.2.3 Cyclosporin A (CsA)……………………………………...24 5.2.2.4 Levamisole………………………………………………..24 5.2.3 結論…………………………………………………………...26 5.3 局部節段性腎絲球硬化 (Focal semential glomerulosclerosis, FSGS) 的藥物治療………………………...28 5.3.1 類固醇………………………………………………………..28 5.3.2 烷基化劑……………………………………………………..31 5.3.3 Cyclosporin (CsA)…………………………………………….31 5.3.4 結論…………………………………………………………..33 5.4 狼瘡性腎炎 (Lupus nephritis, LN) 的藥物治療………………..34 5.4.1 類固醇………………………………………………………..34 5.4.2 Cyclophosphamide (CYC)……………………………..……..35 5.4.3 Azathiopurine (AZA)…………………………………………36 5.4.4 結論………………………………………………………….36 第六節 Mycophenolate Mofetil (MMF)…………………………………..39 6.1 藥理機轉……………………………………………………………40 6.2 藥動學特性…………………………………………………………43 6.2.1 吸收與分布…………………………………………………….43 6.2.2 代謝與排除…………………………………………………….46 6.3 藥物交互作用………………………………………………………47 6.4 副作用………………………………………………………………47 6.5 MMF用於GN的臨床治療………………………………………...48 6.5.1 背景…………………………………………………………….48 6.5.2 以MMF治療GN的可能機轉………………………………..49 6.5.3 MMF在原發性GN的臨床研究………………………………50 6.5.4 MMF在LN的臨床研究………………………………………54 第參章 研究目的…………………………………………………………….58 第肆章 研究方法…………………………………………………………….59 第一節 研究設計………………………………………………………….59 1.1研究類型……………………………………………...……………..59 1.2研究時間及對象…………………………………………………….59 1.3納入標準…………………………………………………………….59 第二節 研究流程………………………………………………………….60 第三節 評估指標與定義………………………………………………….61 3.1 主要評估指標 (primary endpoint)…………………………………61 3.2 次要評估指標 (secondary endpoint)………………………………61 3.3 評估指標之定義……………………………………………………61 3.4 紀錄方法……………………………………………………………63 第四節 統計方法…………………………………………………………64 4.1 統計模式設定……………………………………………………..64 4.2 資料分析方法……………………………………………………..64 4.3 統計軟體…………………………………………………………..64 第伍章 研究結果……………………………………………………………65 第一節 研究對象…………………………………………………………65 第二節 治療效果…………………………………………………………68 2.1 MN患者的MMF治療效果……………………………………….71 2.2 MCD患者的MMF之治療效果…………………………………..74 2.3 其他患者使用MMF之治療效果…………………………………77 第三節 單變項分析 ……………………………………………………..79 第四節 多變項分析………………………………………………………79 第六章 討論…………………………………………………………………82 第一節 研究對象…………………………………………………………82 第二節 MMF用於頑固性腎絲球腎炎的臨床療效……………………..83 2.1以MMF治療MN的效果…………………………………………84 2.2 以MMF治療MCD的效果………………………………………87 2.3 以MMF治療FSGS、IgAN和LN的效果………...……………89 第三節 以MMF治療GN的劑量與療程……………………………….91 第四節 併用藥品之使用…………………………………………………93 第五節 影響MMF治療後DPL降低的因子…………………………...94 第六節 MMF治療之副作用……………………………………………..96 第七節 研究限制…………………………………………………………97 第八節 未來研究方向……………………………………………………98 第柒章 結語…………………………………………………………………....99 參考文獻………………………………………………………………………100 附錄一 病患紀錄表格………………………………………………………..111 第二篇 臨床藥事服務 (Clinical Service)……………………………………113 一、目的………………………………………………………………………113 二、方法………………………………………………………………………113 三、紀錄方式…………………………………………………………………113 四、結果………………………………………………………………………114 第一節 腎衰竭患者的常見疾病與藥物治療…………………………….114 1.1急性腎衰竭 (Acute renal failure, ARF)…………………………….114 1.1.1 定義……………………………………………………………114 1.1.2 急性腎衰竭相關之危險因子…………………………………115 1.1.3 急性腎衰竭的分類和治療……………………………………116 1.1.4 急性腎衰竭相關檢驗數值的變化 (鑑別診斷)………………116 1.1.5 急性腎衰竭電解質異常的治療……………………………….117 1.1.6 急性腎衰竭的預防…………………………………………….118 1.2慢性腎衰竭 (chronic renal failure, CRF)……………………………119 1.2.1 慢性腎病 (chronic kidney disease, CKD) 之定義……………119 1.2.2 常見併發症與治療…………………………………………….120 1.2.3 慢性腎衰竭患者藥物治療注意事項………………………….124 1.3 血液透析 (Hemodialysis)…………………………………………..125 第二節 藥物諮詢…………………………………………………………..127 2.1 抗生素治療相關問題………………………………………………129 2.1.1腎衰竭患者預防術後感染抗生素之使用……………………..129 2.1.2 Teicoplanin用於CAPD患者腹膜炎的劑量…………………130 2.1.3血液透析患者抗結核藥物的使用……………………………131 2.1.4 Isepamicin 在透析患者的使用……………………………….133 2.2 腎病症候群患者的利尿劑治療…………………………………..135 2.3 腎功能不全患者的降血糖藥物…………………………………..138 第三節 藥物不良反應評估………………………………………………140 五 結語……………………………………………………………………….141 參考文獻……………………………………………………………………... 142 表目錄 第一部分 腎絲球腎炎之藥物治療 表一 原發性腎絲球腎炎之組織學分類…………………………………3 表二 次發性腎絲球腎炎之分類…………………………………………3 表三 腎絲球腎炎以腎病症候群以及腎炎症候群表現的傾向…………8 表四 腎絲球腎炎與診斷之特殊血清免疫學標記………………………9 表五 腎絲球腎炎藥物治療的重大發展………………………………11 表六 研究證據強度之分級 (Level of evidence for studies )…………12 表七 建議等級 (Grades of recommendations)…………………………12 表八 以類固醇 (pednisolone) 治療原發性MN的臨床研究…………15 表九 免疫抑制劑治療MN的控制性試驗……………………………19 表十 以類固醇治療局部節段性腎絲球硬化症（FSGS）患者 (療程大於六個月) 的研究報告…………………………………30 表十一 狼瘡性腎炎 (LN) 的WHO病理分類 …………………………37 表十二 以Cyclophophamide和azathiopurine治療狼瘡性腎炎 (LN) 之隨機控制研 (RCT)……………………………………………38 表十三 一般健康者和器官移植患者的口服MMF藥動學參數 ………44 表十四 口服一公克MMF在特殊族群的藥動學參數 …………………45 表十五 MMF治療原發性GN的非控制性試驗…………………………53 表十六 MMF治療LN的非控制性試驗…………………………………57 表十七 17位接受MMF治療腎絲球腎炎病患之基本資料……………66 表十八 17位病患之基本資料以及MMF使用之療程與劑量…………67 表十九 全部病患以及各組中，接受MMF治療前後每日尿液 流失蛋白量 (DPL)、血清肌酐酸 (SCr)、肌酸酐廓清 率 (creatinine clearance, CrCl)、白蛋白 (albumin) 和 膽固醇 (choletserol) 的變化，以平均值 (�b 標準差) 和中位數 (範圍) 表示。……………………………………………………70 表二十 膜性腎病變 (MN) 患者接受MMF治療之過程…………………73 表二十一 五位微細腎病變 (MCD) 患者接受MMF治療之過程…………76 表二十二 FSGS、IgA和LN患者使用MMF治療之過程…………………78 表二十三 17位GN患者接受MMF治療後，DPL降低與變異 因子之單變項分析…………………………………………………………80 表二十四 17位GN患者接受MMF治療後，DPL降低與變異因子 之多變相分析…………………………………………………………………81 表二十五 復發MN患者以MMF治療和追蹤…………………………………86 第二部分 臨床藥事服務 表一 九十一年十月份至九十二年四月份藥物諮詢項目之統計………127 表二 九十一年十月份至九十二年四月份藥物不良反應評估統計……140 附錄表格…………………………………………………………………………145 圖目錄 圖一 腎絲球腎炎的調控機制…………………………………………………5 圖二 MCD的藥物治療………………………………………………………27 圖三 MMF與MPA的化學結構……………………………………………39 圖四 MMF與其他免疫抑制劑藥理作用位置………………………………41 圖五 MMF作用機轉與嘌呤生合成路徑……………………………………42 圖六 MMF的體內代謝過程…………………………………………………46 圖七 MMF治療GN的可能機轉……………………………………………49 圖八 (A)每日尿液流失蛋白量 (DPL)、(B) 血清肌酐酸 (SCr)、 (B)肌酐酸廓清率 (CCr)、(D) 血清白蛋白 (serum albumin)、 (E) 膽固醇 (choletserol) 在MMF治療前後的變化……………69 圖九 MN病患在MMF治療前後DPL的變化…………………………………72 圖十 MCD病患在MMF治療前後DPL的變化………………………………75

    第一篇　腎絲球腎炎的藥物治療

    1. United Sates Renal Data System 2002 annual data report. American journal of kidney diseases 2003; 41:S1-255.

    2. 中央健保局. 八十九年重大傷病門診住院費用統計表 http://www.nhi.gov.tw/07information/news/data/90/news0912.htm. Vol. 2003, 2001.

    3. 中央健保局. 西醫基層第一級總額分配 http://www.nhi.gov.tw/07information/bbs/bbs0103.htm. Vol. 2003, 1999.

    4. 中央健保局. 健保審字第0920020854號 http://www.nhi.gov.tw/07information/bbs/bbs0103.htm, 2003.

    5. Hwang SJ, Yang WC, the Dialysis Surverllance Committee. 1999 national dialysis surverllance in Taiwan. Acta Nephrogica 2000; 14:139-228.

    6. Couser WG. Pathogenesis of glomerular damage in glomerulonephritis. Nephrology Dialysis Transplantation 1998; 13:S10-15.

    7. Couser WG. Glomerulonephritis. Lancet 1999; 353:1509-15.

    8. Glassock RJ. Glomerular therapeutics: looking back, looking forward. Heart Dis 2001; 3:276-81.

    9. Cattran DC. Introduction. Kidney International 1999; 55:S1-2.

    10. Hogan SL, Muller KE, Jennette JC, Falk RJ. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am J Kidney Dis 1995; 25:862-75.

    11. Schieppati A, Mosconi L, Perna A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy. N Engl J Med 1993; 329:85-9.

    12. Reichert LJ, Koene RA, Wetzels JF. Prognostic factors in idiopathic membranous nephropathy. Am J Kidney Dis 1998; 31:1-11.

    13. A controlled study of short-term prednisone treatment in adults with membranous nephropathy. Collaborative Study of the Adult Idiopathic Nephrotic Syndrome. N Engl J Med 1979; 301:1301-6.

    14. Cameron JS, Healy MJ, Adu D. The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party. Q J Med 1990; 74:133-56.

    15. Cattran DC, Delmore T, Roscoe J, et al. A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy. N Engl J Med 1989; 320:210-5.

    16. Controlled trial of azathioprine and prednisone in chronic renal disease. Report by Medical Research Council Working Party. Br Med J 1971; 2:239-41.

    17. Controlled trial of azathioprine in the nephrotic syndrome secondary to idiopathic membranous glomerulonephritis. Can Med Assoc J 1976; 115:1209-10.

    18. Donadio JV, Jr., Holley KE, Anderson CF, Taylor WF. Controlled trial of cyclophosphamide in idiopathic membranous nephropathy. Kidney Int 1974; 6:431-9.

    19. West ML, Jindal KK, Bear RA, Goldstein MB. A controlled trial of cyclophosphamide in patients with membranous glomerulonephritis. Kidney Int 1987; 32:579-84.

    20. Murphy BF, McDonald I, Fairley KF, Kincaid-Smith PS. Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis. Clin Nephrol 1992; 37:229-34.

    21. Ponticelli C, Zucchelli P, Imbasciati E, et al. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med 1984; 310:946-50.

    22. Ponticelli C, Zucchelli P, Passerini P, Cesana B. Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group. N Engl J Med 1992; 327:599-603.

    23. Ponticelli C, Zucchelli P, Passerini P, et al. A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy. Kidney Int 1995; 48:1600-4.

    24. Imperiale TF, Goldfarb S, Berns JS. Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials. J Am Soc Nephrol 1995; 5:1553-8.

    25. Ponticelli C, Altieri P, Scolari F, et al. A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy. J Am Soc Nephrol 1998; 9:444-50.

    26. Talar-Williams C, Hijazi YM, Walther MM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996; 124:477-84.

    27. Cattran DC, Greenwood C, Ritchie S, et al. A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group. Kidney Int 1995; 47:1130-5.

    28. Nephrotic syndrome in children: a randomized trial comparing two prednisone regimens in steroid-responsive patients who relapse early. Report of the international study of kidney disease in children. J Pediatr 1979; 95:239-43.

    29. Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. A report of "Arbetsgemeinschaft fur Padiatrische Nephrologie". Lancet 1979; 1:401-3.

    30. Ehrich JH, Brodehl J. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Eur J Pediatr 1993; 152:357-61.

    31. Tarshish P, Tobin JN, Bernstein J, Edelmann CM, Jr. Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 1997; 8:769-76.

    32. Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic syndrome of childhood. Lancet 1970; 2:479-82.

    33. Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children. Lancet 1974; 2:423-7.

    34. Barratt TM, Cameron JS, Chantler C, Ogg CS, Soothill JF. Comparative trial of 2 weeks and 8 weeks cyclophosphamide in steroid- sensitive relapsing nephrotic syndrome of childhood. Arch Dis Child 1973; 48:286-90.

    35. Grupe WE, Makker SP, Ingelfinger JR. Chlorambucil treatment of frequently relapsing nephrotic syndrome. N Engl J Med 1976; 295:746-9.

    36. Williams SA, Makker SP, Ingelfinger JR, Grupe WE. Long-term evaluation of chlorambucil plus prednisone in the idiopathic nephrotic syndrome of childhood. N Engl J Med 1980; 302:929-33.

    37. Effect of cytotoxic drugs in frequently relapsing nephrotic syndrome with and without steroid dependence. N Engl J Med 1982; 306:451-4.

    38. Tejani A, Suthanthiran M, Pomrantz A. A randomized controlled trial of low-dose prednisone and ciclosporin versus high-dose prednisone in nephrotic syndrome of children. Nephron 1991; 59:96-9.

    39. Ponticelli C, Edefonti A, Ghio L, et al. Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant 1993; 8:1326-32.

    40. Pei Y, Cattran D, Delmore T, Katz A, Lang A, Rance P. Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis. Regional Glomerulonephritis Registry Study. Am J Med 1987; 82:938-44.

    41. Rydel JJ, Korbet SM, Borok RZ, Schwartz MM. Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. Am J Kidney Dis 1995; 25:534-42.

    42. Meyrier A, Noel LH, Auriche P, Callard P. Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Societe de Nephrologie. Kidney Int 1994; 45:1446-56.

    43. Ittel TH, Schmitt H, Mrowka C, Sieberth HG. Cyclosporine long-term treatment of minimal-change nephrotic syndrome (MCNS) with cyclosporin A: is there a loss of efficacy? (abstrate). Journal of the American Society of Nephrology 1993; 4:278.

    44. Austin HA, 3rd, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314:614-9.

    45. Boumpas DT, Austin HA, 3rd, Vaughn EM, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992; 340:741-5.

    46. Gourley MF, Austin HA, 3rd, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996; 125:549-57.

    47. Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135:248-57.

    48. Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med 1984; 311:1528-33.

    49. Bansal VK, Beto JA. Treatment of lupus nephritis: a meta-analysis of clinical trials. Am J Kidney Dis 1997; 29:193-9.

    50. Nossent HC, Koldingsnes W. Long-term efficacy of azathioprine treatment for proliferative lupus nephritis. Rheumatology (Oxford) 2000; 39:969-74.

    51. Lee WA, Gu L, Miksztal AR, Chu N, Leung K, Nelson PH. Bioavailability improvement of mycophenolic acid through amino ester derivatization. Pharm Res 1990; 7:161-6.

    52. Carr SF, Papp E, Wu JC. Characterization of human type I and type II IMP dehydrogenases. The Journal of Biological Chemistry 1993; 268:27286-90.

    53. Mycophenolate mofetil prescribing information: Hoffmann-La Roche Inc, 2000.

    54. Allison AC, Eugui EM. The design and development of an immunosuppressive drug, mycophenolate mofetil. Springer Semin Immunopathol 1993; 14:353-80.

    55. Burnham TH. Drugs fact and comparison. Missouri: A Wolters Kluwer Company, 2002.

    56. Hauser IA, Renders L, Radeke HH, Sterzel RB, Goppelt-Struebe M. Mycophenolate mofetil inhibits rat and human mesangial cell proliferation by guanosine depletion. Nephrology Dialysis Transplantation 1999; 14:58-63.

    57. Raisanen-Sokolowski A, Vuoristo P, Myllarniemi M, Yilmaz S, Kallio E, Hayry P. Mycophenolate mofetil (MMF, RS-61443) inhibits inflammation and smooth muscle cell proliferation in rat aortic allografts. Transpl Immunol 1995; 3:342-51.

    58. Nagy SE, Andersson JP, Andersson UG. Effect of mycophenolate mofetil (RS-61443) on cytokine production: inhibition of superantigen-induced cytokines. Immunopharmacology 1993; 26:11-20.

    59. Badid C, Vincent M, McGregor B, et al. Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney. Kidney Int 2000; 58:51-61.

    60. Cohn RG, Mirkovich A, Dunlap B, et al. Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines. Transplantation 1999; 68:411-8.

    61. Blaheta RA, Leckel K, Wittig B, et al. Inhibition of endothelial receptor expression and of T-cell ligand activity by mycophenolate mofetil. Transpl Immunol 1998; 6:251-9.

    62. Heemann U, Azuma H, Hamar P, Schmid C, Tilney N, Philipp T. Mycophenolate mofetil inhibits lymphocyte binding and the upregulation of adhesion molecules in acute rejection of rat kidney allografts. Transpl Immunol 1996; 4:64-7.

    63. Zatz R, Noronha IL, Fujihara CK. Experimental and clinical rationale for use of MMF in nontransplant progressive nephropathies. American Journal of Physiology : Renal Physiology 2002; 283:F1167-75.

    64. Briggs WA, Choi MJ, Scheel PJ, Jr. Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 1998; 31:213-7.

    65. Briggs WA, Choi MJ, Scheel PJ. Follow-up on mycophenolate treatment of glomerular disease. American Journal of Kidney Diseases 1998; 32:898-9.

    66. Miller G, Zimmerman R, 3rd, Radhakrishnan J, Appel G. Use of mycophenolate mofetil in resistant membranous nephropathy. Am J Kidney Dis 2000; 36:250-6.

    67. Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D. Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 2002; 17:2011-3.

    68. Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 2002; 61:1098-114.

    69. Corna D, Morigi M, Facchinetti D, Bertani T, Zoja C, Remuzzi G. Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease. Kidney Int 1997; 51:1583-9.

    70. Van Bruggen MC, Walgreen B, Rijke TP, Berden JH. Attenuation of murine lupus nephritis by mycophenolate mofetil. J Am Soc Nephrol 1998; 9:1407-15.

    71. Zoja C, Benigni A, Noris M, et al. Mycophenolate mofetil combined with a cyclooxygenase-2 inhibitor ameliorates murine lupus nephritis. Kidney Int 2001; 60:653-63.

    72. Glicklich D, Acharya A. Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am J Kidney Dis 1998; 32:318-22.

    73. Gaubitz M, Schorat A, Schotte H, Kern P, Domschke W. Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Lupus 1999; 8:731-6.

    74. Dooley MA, Cosio FG, Nachman PH, et al. Mycophenolate mofetil therapy in lupus nephritis: clinical observations. J Am Soc Nephrol 1999; 10:833-9.

    75. Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000; 343:1156-62.

    76. Contreras G, Roth D, Berho M. Immunosuppressive therapy for proliferative lupus nephritis: Preliminary report of a prospective randomized clinical trail with mycophenolate mofetil. Journal of the American Society of Nephrology 1999; 10:507A.

    77. Ziswiler R, Steinmann-Niggli K, Kappeler A, Daniel C, Marti HP. Mycophenolic acid: a new approach to the therapy of experimental mesangial proliferative glomerulonephritis. J Am Soc Nephrol 1998; 9:2055-66.

    78. Johnson AG, Rigby RJ, Taylor PJ, et al. The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients. Clin Pharmacol Ther 1999; 66:492-500.

    第二篇　臨床藥事服務(Clinical Service)

    1. Applied therapeutics: the clinical use of drugs. In: Thomas JC, ed. Reanl Disorder. Philadelphia: Lippincott Williams & Wilkins, 2001:29.1-33.50.

    2. Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. Can Med Assoc J 2002; 166:473-7.

    3. Ifudu O. Care of patients undergoing hemodialysis. N Engl J Med 1998; 339:1054-62.

    4. Star RA. Treatment of acute renal failure. Kidney Int 1998; 54:1817-31.

    5. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med 1996; 334:1448-60.

    6. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343:180-4.

    7. Winter WE. Basic clinical pharmacokinetics. Vancouver,WA: Applied Therapeutics, 1999:104-113.

    8. Rowland M, Tozer TN. . Clinical pharmacokinetics. Concepts and applications. Baltimore: Williams & Wilkins, 1995:443-62.

    9. Aronoff GR, Berns JS, M.E. B, et al. Drug prescribing in renal failure: Dosing guidelines for adults. Philadelphia: Ameriacn College of Physicians, 1999.

    10. Atkinson AJ, Susla GM. Pharmacokinetics in rebnal replacement therapy. Principles of clinical pharmacology. San Diego: Academic press, 2001:51-62.

    11. Drug information handbook, 2003.

    12. MICROMEDEX 2003. .

    13. Keane WF, Bailie GR, Boeschoten E, et al. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.

    14. Brouard RJ, Kapusnik JE, Gambertoglio JG, et al. Teicoplanin pharmacokinetics and bioavailability during peritoneal dialysis. Clin Pharmacol Ther 1989; 45:674-81.

    15. Schaefer F, Klaus G, Muller-Wiefel DE, Mehls O. Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS). J Am Soc Nephrol 1999; 10:136-45.

    16. Malone RS, Fish DN, Spiegel DM, Childs JM, Peloquin CA. The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol.Am J Respir Crit Care Med 1999; 159:1580-4.

    17. Ellard GA. Chemotherapy of tuberculosis for patients with renal impairment. Nephron 1993; 64:169-81.

    18. Barr WH, Colucci R, Radwanski E, et al. Pharmacokinetics of isepamicin.J Chemother 1995; 7 Suppl 2:53-61.

    19. Wilcox CS. New insights into diuretic use in patients with chronic renal disease. J Am Soc Nephrol 2002; 13:798-805.

    20. Ichikawa I, Rennke HG, Hoyer JR, et al. Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest 1983; 71:91-103.

    21. Humphreys MH. Mechanisms and management of nephrotic edema. Kidney Int 1994; 45:266-81.

    22. Inoue M, Okajima K, Itoh K, et al. Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients. Kidney Int 1987;32:198-203.

    23. Chehade JM, Mooradian AD. A rational approach to drug therapy of type 2 diabetes mellitus. Drugs 2000; 60:95-113.

    24. Rosiglitazone product information. 2002.

    25. Repaglinide product information. 2002.

    26. Rabkin R, Ryan MP, Duckworth WC. The renal metabolism of insulin.Diabetologia 1984; 27:351-7.

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