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研究生:許杏如
研究生(外文):Hsing-Ju Sheu
論文名稱:甲型免疫球蛋白腎病變之治療
論文名稱(外文):Treatment of IgA Nephropathy
指導教授:黃建鐘黃建鐘引用關係高雅慧高雅慧引用關係
指導教授(外文):Jeng-Jong HuangYea-Huei Kao Yang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:121
中文關鍵詞:血管張力素轉換酵素抑制劑第二型血管張力素拮抗劑魚油免疫抑制劑類固醇重度蛋白尿甲型免疫球蛋白腎病變
外文關鍵詞:IgA Nephropathyheavy proteinuriasteroidangiotensin converting enzyme inhibitorangiotensinⅡantagonistfish oilimmunosuppressive agent
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甲型免疫球蛋白腎病變 (IgA nephropathy, IgAN) 是全世界最常見的腎絲球腎炎(glomerulonephritis, GN),發生在各個年齡層,但以二十至三十歲的成人居多,男女的比例為二至三比一。病因仍無定論,可能根源於IgA系統本身的異常。臨床表現為無痛性肉眼血尿、顯微血尿、蛋白尿或腎功能逐漸衰退。約有20%的病患,二十年後進入末期腎病(end-stage renal disease, ESRD);臨床及病理學上的不良預後指標,包括:發病初期即有腎功能不良或高血壓者,重度或達腎病症侯群蛋白尿(heavy or nephrotic-ranged proteinuria)者,病理切片呈現腎小管間質病變(tubulointerstitial nephritis,TIN)或腎絲球有半月體(crescent)生成者。關於IgAN的藥物治療,目前臨床證據顯示,類固醇可減輕蛋白尿的嚴重度,並使腎功能維持穩定。高血壓的病患, 使用ACEIs為首要選擇;在血壓正常患者,有減輕蛋白尿的益處。另外,臨床研究發現,富含長鏈omega-3-多元不飽合脂肪酸的魚油 (fish oil),可改善IgAN的病程,也有報告指出類固醇合併cyclophospamide治療,可以減緩IgAN病程的進展。
因重度蛋白尿是影響IgAN預後的一個重要因子,使用類固醇和ACEIs/AⅡAs治療皆能有效地降低蛋白尿,所以我們進行一回溯性研究,探討成大醫院具重度蛋白尿 (每天尿蛋白流失量大於三公克) 的IgAN患者,對類固醇及ACEIs/AⅡAs的治療反應。根據腎臟病理切片報告,收集102位IgAN病患,研究期間由確立病理診斷追蹤至2001/12/31;採病歷回顧方式,排除26位失去追蹤、7位過敏性紫斑 (HSP)和9位年齡小於16歲的病患,分析60位IgAN患者的臨床表現、用藥和生化檢驗數據變化。在確立診斷時其中33位為輕、中度蛋白尿,另27位為重度蛋白尿患者。在這27位中,排除3位檢驗數據不全和2位無使用這兩項藥品的病患,有8位使用類固醇,8位使用ACEIs/AⅡAs和6位合併使用兩者。我們分析此三種不同治療方式,對蛋白尿的改善程度,發現單獨使用類固醇或ACE Is/AⅡAs,可降低約40%的蛋白尿,合併治療組可降低約60%。降低蛋白尿成效,三組比較沒有統計學差異。本研究的最大限制為病患人數少,而且無排除不良預後因子對結果的影響,是否類固醇合併ACEIs/AⅡAs治療重度蛋白尿患者,能達到較好的成效,仍需以更多患者及前瞻性試驗加以佐證。
IgA nephropathy (IgAN) is the most common form of primary glomerulonephpritis worldwide. It occurs at all ages, with the usual age of cilinical onset in the second and third decade of life. There is usual male predilection ranging from 2-3 to 1. The pathogenesis of IgAN is not clear, it may be due to the abnormality of IgA system. Typically, IgAN presents with painless macroscopic or microscopic hematuria, proteinuria, and gradual deterioration of renal function. In the clinical course, there are about 20 % patients with progressive renal failure after 20 years. Renal insufficeincy or hypertension in the beginning of disease, heavy proteinuria, and the pathological findings with tubulointerstitial nephritis (TIN) or crescents formation in glomuruli are poor prognostic factors of IgAN. From the previous studies, treatment with corticosteroids could decrease proteinuria and stabilize renal function. Angiotensin converting enzyme inhibitors (ACEIs) are the first choice of therapy for IgAN patients with hypertension, and there is also benefit of decreasing proteinuria for normotensive patients. Fish oil, which is rich in omega-3 polyunsaturated fatty acid, can prevent IgAN progression. In addition, steroid combined with cyclophospamide therapy was also effective.
Because heavy proteinuria is an important prognostic factor of IgAN, it is worth to investigate the therapeutic responses of corticosteroids and ACEIs/AⅡAs in IgAN patients with heavry proteinuria (daily protein loss ³ 3 g). Therefore, a retrospective study was conducted in Division of Nephrology, Department of Internal Medicine, National Cheng Kung Unervisity Hospital. The observation period was from the date of definite pathological diagnosis to 2001/12/31. We have reviewed and analyzed the medications, changes of clinical and laboratory tests from the medical record. The total number of IgAN patients was 102, but 42 patients were excluded, due to: lost of follow-up (26), HSP (7) and children (9). Totally, 60 patients were included in this study with a mean observation period of 45 months. Thirty-three of them presented with moderate proteinuria and 27 with heavy proteinuria. Among the 27 patients, 8 were treated with steroid alone, 8 with ACEIs/AⅡAs alone and other 6 with both agents. Five patients were excluded (2 had incomplete laboratory data and others were managed without both drugs.). We found that steroid or ACEIs/AⅡAs therapy alone could averagely had 40 %decrease of urinary protein excretion and 60 % in combined treatment. However, treatment efficacy between these three groups had no significant difference.
In the future work, we need a prospective study with more patient number to prove that combined treatment of steroid and ACEIs/AⅡAs is more effective in IgAN patients with heavy proteinuria.
中文摘要Ⅰ
英文摘要 Ⅲ
誌謝 Ⅳ
目錄 Ⅵ
表目錄 Ⅹ
圖目錄 ⅩⅢ
縮寫 ⅩⅤ

第壹篇、前言 1
第貳篇、文獻回顧 2
第一章、流行病學 2
第二章、臨床表徵 3
第三章、診斷 5
第四章、病因和病理機轉 6
第五章、病理變化 8
第六章、合併疾病 10
第七章、預後因子 12
第八章、治療 15
第一節、 類固醇(Glucocorticoids) 17
1.1、治療重度蛋白尿IgAN患者 21
1.2、治療中度蛋白尿IgAN患者 26
1.3、治療輕度蛋白尿IgAN患者 32
第二節、血管張力素轉換酵素抑制劑(Angiotensin converting enzyme inhibitors,ACEIs) 和第二型血管張力素拮抗劑(angiotensinⅡantagonists, AⅡAs) 34
2.1、治療高血壓IgAN患者 37
2.2、治療正常血壓IgAN患者 41
2.3、ACEIs和AⅡAs合併治療 44
第三節、 魚油(Fish oil) 46
第四節、免疫抑制劑(immunosuppressive agents) 58
4.1、Cyclosporine A 60
4.2、Cyclophosphamide 63
4.3、Azathioprine 71
第五節、其他 74

第參篇、回顧性臨床研究(A retrospective clinical study) 75
第一章、研究背景 75
第二章、研究目的 76
第三章、研究方法 77
第一節、研究對象 77
第二節、研究執行 77
第三節、研究評估指標 78
第四節、統計方法 79
第四章、研究結果 80
第五章、討論 90
第一節、 IgAN患者伴隨重度蛋白尿之臨床表現 90
第二節、 類固醇與ACEIs/AⅡAs治療之成效 92
第三節、 病患對治療無反應之評估 94
第四節、 研究之限制 95
第五節、未來研究方向 96
第肆篇、結論及建議 97
參考文獻 101

附錄
附錄一、腎臟科臨床實習、藥事服務及專題寫作 108
附錄二、成大醫院臨床藥事服務個案記錄表 114
附錄三、成大醫院臨床藥事服務工作記錄表 115
附錄四、藥物不良反應通報表 116
附錄五、藥物不良反應事件評估表 117
附錄六、成大醫院藥物不良反應評估表 118
附錄七、IgAN臨床研究個案記錄表(1) 119
附錄八、IgAN臨床研究個案記錄表(2) 120
附錄九、IgAN臨床研究個案記錄表(3) 121
1.Allen A.C., Bailey E.M., Buck K.S., et al. O-glycosylation of mesangial IgA1 in IgA nephropathy. J Am Soc Nephrol 10:506A, 1999.
2.Berger J., Hinglais N. Les depots intercapillaries d’IgA-IgG. J Urol Nephrol 74: 694-5, 1968.
3.Bennett W.M., Walker R.G., Smith P.K. Treatment of IgA nephropathy with eicosapentanoic acid (EPA): a two-year prospective trial. Clin Nephrol 31(3): 128-31, 1989.
4.Buemi M., Allegra A., Corica F., et al. Effect of fluvastatin on proteinuria in patients with immunoglobulin A nephropathy. Clin Pharmacol Ther 67(4): 427-31, 2000.
5.Bartosik L.P., Lajoie G., Sugar L., Cattran D.C. Predicting progression in IgA nephropathy. Am J Kidney Dis.38 (4): 728-35, 2001.
6.Clarkson A.R., Seymour A.E., Woodroffe A.J., et al. Controlled trial of phenytoin therapy in IgA nephropathy. Clin Nephrol 13(5): 215-8, 1980.
7.Coppo R., Basolo B., Giachino O., et al. Plasmapheresis in a patient with rapidly progressive idiopathic IgA nephropathy: removal of IgA-containing circulating immune complexes and clinical recovery. Nephron 40(4): 488-90, 1985.
8.Cheng R.K.P., Chan P.C.K., Chan M.K. The effect of fish-oil dietary supplement on the progression of mesangial IgA glomerulonephritis. Nephrol Dial Transplant 5(4): 241-6, 1990.
9.Coppo R., Roccatello D., Amore A., et al. Effects of a gluten-free diet in primary IgA nephropathy. Clin Nephrol 33(2): 72-86, 1990.
10.Cattran D.C., Greenwood C., Ritchie S. Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. Am J Kidney Dis 23(2): 247-54, 1994.
11.Cattran D.C. Introduction. Kidney Int 55(suppl. 70): S1-2, 1999.
12.Damico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med 64(245): 709-27, 1987.
13.Davison A.M. Steroid therapy in primary glomerulonephritis.
Nephrol Dial Transplant 5 Suppl 1:23-8, 1990.
14.Donadio J.V., Bergstralh E.J., Offord K.P., et al. A controlled trial of fish oil in IgA nephropathy. Mayo Nephrology Collaborative Group. N Engl J Med 331(18): 1194-9, 1994.
15.Donadio J.V., Grande J.P. Immunoglobulin A nephropathy: a clinical perspective. J Am Soc Nephrol 8(8): 1324-32,1997.
16.Donadio J.V., Grande J.P., Bergstralh E.J., et al. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. J Am Soc Nephrol 10(8): 1772-7, 1999.
17.Damico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis 36(2): 227-37, 2000.
18.Donadio J.V., Larson T.S., Bergstralh E.J., et al. A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. J Am Soc Nephrol 12(4): 791-9, 2001.
19.Donadio J.V. The emerging role of omega-3 polyunsaturated fatty acids in the management of patients with IgA nephropathy. J Ren Nutr 11(3): 122-8, 2001.
20.Egido J., Rivera F., Sancho J., Barat A. and Hernando L. Phenytoin in IgA nephropathy: a long-term controlled trial. Nephron 38(1): 30-9, 1984.
21.Epstein F.H. Pathophysiology of progressive nephropathies. N Engl J Med 339 (20): 1448-56, 1998.
22.Ferri C., Puccini R., Longombardo G., et al. Low-antigen-content diet in the treatment of patients with IgA nephropathy. Nephrol Dial Transplant 8(11): 1193-8, 1993.
23.Floege J. and Feehally J. IgA nephropathy: recent developments. J Am Soc Nephrol 11(12): 2395-403, 2000.
24.Galla J.H. IgA nephropathy. Kidney Int 47(2): 377-87, 1995.
25.Goumenos D., Ahuja M., Shortland J.R. and Brown C.B. Can immunosuppressive drugs slow the progression of IgA nephropathy? Nephrol Dial Transplant 10: 1173-81, 1995.
26.Grand J.P., and Donadio J.V. Dietary fish oil supplementation in IgA nephropathy: a therapy in search of a mechanism? Nutrition 14(2): 240-2, 1998.
27.Gunter W. Molecular mechanism of angiotensin Ⅱin the kidney: emerging role in the progression of renal disease: beyond haemodynamics. Nephrol Dial Transplant 13: 1131-1142, 1998.
28.Hamazaki T., Tateno S. and Shishido H. Eicosapentaenoic acid and IgA nephropathy. Lancet 1(8384): 1017-8, 1984.
29.Hotta O., Taguma Y., Yoshizawa N., et al. Long-term effects of intensive therapy combined with tonsillectomy in patients with IgA nephropathy. Acta Otolaryngol Suppl 523:165-8, 1996.
30.Harper L., Savage C.O.S. Treatment of IgA nephropathy. Lancet 353(9156): 860-2, 1999.
31.Haramaki R., Tamaki K., Fujisawa M., et al. Steroid therapy and urinary transforming growth factor-beta1 in IgA nephropathy. Am J Kidney Dis 38(6): 1191-8, 2001.
32.Ibels L.S., Gyory A.Z., Caterson R.J. Primary IgA nephropathy: natural history and factors of importance in the progression of renal impairment. Kidney Int 52 (suppl): S67-70, 1997.
33.Julian B.A. Treatment of IgA nephropathy. Semin Nephrol 20 (3): 277-85, 2000.
34.Kobayashi Y. Fujii K., Hiki Y., et al. Steroid therapy in IgA nephropathy: a retrospective study in heavy proteinuric cases. Nephron 48(1): 12-7,1988.
35.Kobayashi Y., Hiki Y., Fujii K., et al. Moderately proteinuric IgA nephropathy: prognostic prediction of individual clinical courses and steroid therapy in progressive cases. Nephron 53(3): 250-6, 1989.
36.Kobayashi Y., Hiki Y., Kokubo T., Horii A. and Tateno S. Steroid therapy during the early stage of progressive IgA nephropathy. A 10-year follow-up study. Nephron 72(2): 237-42, 1996.
37.Kokubo T, Hiki Y., Iwase H., et al. Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins. J Am Soc Nephrol 9: 2048-54, 1998.
38.Lai K.N., Lai F.M., Ho C.P.and Chan K.W. Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. Clin Nephrol 26(4): 174-80, 1986.
39.Lai K.N., Lai M.M., Owen J.V. A short-term controlled trial of cyclosporine A in IgA nephropathy. Transplant Proc 20(3 Suppl 4): 297-303, 1988
40.Lee S.M.K. Prognostic indicators of progressive renal disease in IgA nephropathy: emergence of a new histologic grading system. Am J Kidney Dis 29:953-8, 1997.
41.Locatelli F., Pozzi C., Vecchio L.D., et al. Role of proteinuria reduction in the progression of IgA nephropathy. Ren Fail 23(3-4): 495-505, 2001.
42.Maschio G., Cagnoli L., Claroni F., et al. ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant 9(3): 265-9, 1994.
43.Mento PF, Wilkes B.M. Plasma angiotensins and blood pressure during converting converting enzyme inhibition. Hypertension 9: S42-48, (suppl Ⅲ), 1987.
44.Miura M., Endoh M., Nomoto Y. and Sakai H. Long-term effect of urokinase therapy in IgA nephropathy. Clin Nephrol 32(5): 209-16, 1989.
45.Matsubara M., Taguma Y., Saito T. and Yoshinga K. Effect of camostat mesilate on persistent proteinuria of IgA nephropathy. Nephron 60(2): 244-5, 1992.
46.Manno C., Gesualdo L., Altri C.D., et al. Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy. J Nephrol 14(4): 248-52, 2001.
47.Mitsioni A. IgA nephropathy in children. Nephrol Dial Transplant 16 Suppl 6:123-5,2001.
48.Nolin L. and Courteau M. Management of IgA nephropathy: evidence-based recommendations. Kidney Int Suppl 70:S56-62, 1999.
49.Okamura M., Kanayama Y., Negoro N., Inoue T., Takeda T. Long-term effects of calcium antagonists and angiotensin-converting enzyme inhibitors in patients with chronic renal failure of IgA nephropathy.
Contrib Nephrol 90:161-5, 1991.
50.Pettersson E.E., Rekola S., Berglund L., et al. Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Clin Nephrol 41(4): 183-90, 1994.
51.Pozzi C., Bolasco P., Fogazzi G., et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353(9156): 883-7, 1999.
52.Russo D., Pisani A., Balletta M.M., et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis 33(5): 851-6, 1999.
53.Rajaram V. and Liapis H. Immunoglobulin A nephropathy. Nephrol Dial Transplant 16 Suppl 6:77-9, 2001.
54.Rekola S., Bergstrand A., Bucht H. Deterioration of GFR in IgA nephropathy as measured by 51Cr-EDTA clearance. Kidney Int 40:1050-4, 1991.
55.Rostoker G., Belghiti D.D., Pilatte Y., et al. High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schonlein purpura. Ann Intern Med 15; 120(6): 476-84, 1994.
56.Ruggenenti P., Perna A., Mosconi L., et al. Randomised placebo- controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 349: 1857-63, 1997.
57.Roccatello D., Ferro M., Cesano G., et al. Steroid and cyclophosphamide in IgA nephropathy. Nephrol Dial Transplant 15(6): 833-5, 2000.
58.Russo D., Minutolo R., Pisani A., et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 38(1): 18-25, 2001.
59.Sato M., Takayama K., Kojima H. and Koshikawa S. Sodium cromoglycate therapy in IgA nephropathy: a preliminary short-term trial.
Am J Kidney Dis 15(2): 141-6, 1990.
60.Shoji T., Nakanishi I., Suzuki A., et al. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis 35(2): 194-201, 2000.
61.Tomino Y., Sakai H.S., Miura M., et al. Effect of danazol on solubilization of immune deposits in patients with IgA nephropathy. Am J Kidney Dis 4(2): 135-40, 1984.
62.Tomino Y., Suzuki S., Imai H., et.al. Measurement of serum IgA and C3 may predict the diagnosis of patients with IgA nephropathy prior to renal biopsy. J Clin Lab Anal 14:220-223, 2000.
63.Tsuruya K., Harada A., Hirakata H., et al. Combination therapy using prednisolone and cyclophosphamide slows the progression of moderately advanced IgA nephropathy. Clin Nephrol 53(1): 1-9, 2000.
64.Urata H, Bohem K.D., Philip A. et.al. Cellular localization and regional distribution of an angiotensin Ⅱ-forming chymase in the heart. J Clin Invest 91:1269-81, 1993.
65.Woo K.T., Edmondson R.P.S., Yap H.K., et al. Effects of triple therapy on the progression of mesangial proliferative glomerulonephritis. Clin Nephrol 27(2): 56-64, 1987.
66.Woo K.T., Lau Y.K., Wong K.S.and Chiang S.C. ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. Kidney Int 58(6): 2485-91, 2000.
67.Walker R.G., Yu S.H., Owen J.E. and Smith P.K. The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin: a two-year prospective trial. Clin Nephrol 34(3): 103-7, 1990.
68.Yoshikawa N., Tanaka R., Iijima K. Pathophysiology and treatment of IgA nephropathy in children. Pediatr Nephrol 16(5): 446-57,2001.
69.Ahya S.N., Flood K., Paranjothi S. The Washington manual of medical therapeutics. Lippincott Williams Wilkins USA. P.269, 2001.
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