小剂量霉酚酸酯联合激素治疗IgA肾病临床观察_《华西医学》

作者：

金巧玲 ,  陶冶 , 尹恒 , 胡章学 , 于笑 , 魏冕

四川大学华西医院肾脏内科（成都，610041）;

关键词：

IgA肾病霉酚酸酯治疗

DOI：

10.7507/1002-0179.20130305

视频：

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目的　回顾性观察糖皮质激素联合小剂量吗替麦考酚酯（MMF）对IgA肾病的临床疗效及安全性。方法　 2010年9月－2012年9月在我科门诊就诊的28例IgA肾病患者接受了小剂量MMF联合激素治疗。醋酸泼尼松起始剂量为0.6 mg/（kg·d），MMF起始剂量为0.5～1.0 g/d，2～4周内调节药物剂量使血药浓度（MPA-AUC）维持在30～60 mg·h/L。治疗前及治疗后每月随访观察血清肌酐、血清白蛋白、尿蛋白定性、24 h尿蛋白定量及药物不良反应等指标。诱导期初定为6个月，若6个月未完全缓解（CR）则延长至9个月，总疗程至少12个月，主要评价指标为诱导治疗期的完全缓解率。结果　全部患者均完成了12个月的随访观察，全组28例中CR 8例（28.6%），部分缓解（PR）14例（50.0%），未缓解（NR）6例（21.4%），总有效率78.6%。随访过程中，3例患者出现呼吸道感染，其中2例住院治疗；2例患者出现尿路感染，1例患者出现腹泻。结论　小剂量MMF治疗IgA肾病安全、有效且能在一定程度上节省患者费用，可作为其他免疫抑制方案治疗无效或复发时的一种治疗选择。

引用本文： 金巧玲,陶冶,尹恒,胡章学,于笑,魏冕. 小剂量霉酚酸酯联合激素治疗IgA肾病临床观察. 华西医学, 2013, 28(7): 978-983. doi: 10.7507/1002-0179.20130305 复制

1.	Luetscher Jr JA, Deming QB, Harvey J, et al. Treatment of nephrosis with cortisone[J]. J Clin Invest, 1950, 29(12): 1576-1587.
2.	Vanderwoude FJ. Mycophenplate mofetil(RS 61443): nothing new under the sun or an important break-through in the field of transplantation? [J]. Nephrol Dial Transpl, 1995, 10(7): 1112-1115.
3.	Huang YF, Liu ZH, Huang HD, et al. Effects of mycophenolic acid on endothelial cells[J]. Int Immunopharmacol, 2005, 5(6): 1029-1039.
4.	Allison AC. Mechanisms of action of mycophenolate mofetil[J]. Lupus, 2005, 14(3): S2-S8.
5.	Apple GB, Radhakrishnan J, Ginzler EM. Use of mycophenolate mofetil in autoimmune and renal diseases[J]. Transplantation, 2005, 80(2): S265-S271.
6.	Mase BD, Oyen R, Claes K, et al. Mycophenolate mofetil in IgA nephropathy: Results of a 3-year prospective placebo-controlled randomized study[J]. Kidney Int, 2004, 65(5): 1842-1849.
7.	Trinidad PR, Meza L, Diaz OA. Mycophenolate mofetil treatment in primary glomerular diseases without response to conventional immunosuppressive agents[J]. J Am Soc Nephrol, 2003, 14(7): 800-812.
8.	Polenakovic M, Grcevska L, Dzikova S. Mycophenolate mofetil in treatment of idiopathic stages IIII-V membranous nephropathy[J]. Nephrol Dial Transpl, 2003, 18(6): 1233-1234.
9.	D’Amcio G. Natural history of idiopathic IgA nephropathy: the role of clinical and histological prognostic factors[J]. Am J Kidney Dis, 2002, 36(2): 227-37.
10.	Tang S, Tang A, Wong S, et al. Long–term study of mycophenolate mofetil treatment in IgA nephropathy[J]. Kidney Int, 2010, 77(6): 543-549.
11.	Groth C, Pichlmayr R, Sadek S, et al. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection[J]. Lancet, 1995, 345(8961): 1321-1325.
12.	Appel GB, Contreras G, Dooley MA, et al. mycophenolate mofetil versus cyclophosphamide for Induction Treatment of Lupus Nephritis[J]. J Am Soc Nephrol, 2009, 20(5): 1103-1112.
13.	陈香美, 陈仆, 蔡广研, 等. 麦考酚酸酯治疗IgA 肾病的随访对照观察[J]. 中华医学杂志, 2006, 82(12): 796-891.
14.	Donadio J, Grande J. IgA nephropathy[J]. N Engl J Med, 2002, 347(10): 738-748.
15.	Galla JH. IgA nephropathy[J]. Kidney Int, 1995, 47(2): 377-387.
16.	Zatz R, Noronha IL, Fujihara CK. Experimental and clinical rationale for use of MMF in nontransplant progressive nephropathies[J]. Am J Physiol Renal Physiol, 2002, 283(6): 1167-1175.
17.	Russo D, Pisani A, Balletta MM, et al. Additive antiproteinuric effect of converting enzyme inhibitor and Losartan in normotensive patients with IgA nephropathy[J]. Am J Kidney Dis, 1999, 33(5): 851-856.
18.	Samuels JA, Strippoli G FM, Craig J C, et al. Immunosuppressive agents for treating IGA nephropathy(Cochrane Review)[J]. Cochrane Database Syst Rev, 2003, (4): CD003965.
19.	Bennett WM, Walke RG, Kincaid-Smith P. Treatment of IgA nephropathy with eicosapentanoic acid: A two-year prospective trial[J]. Clin Nephrol, 1989, 31(3): 128-131.
20.	Pettersson EE, Rekola S, Berglund L, et al. Treatment of IgA nephropathy with omega-3 polysaturated fatty acids: a prospective, double-blind, randomised study[J]. Clin Nephrol, 1994, 41(4): 183-190.
21.	Donadio JV Jr, Bergstralh EF, Offord KP, et al. A controlled trial of fish oil in IgA nephropathy[J]. N Engl J Med, 1994, 331(18): 1194-1199.
22.	Donadio JV Jr, Larson TS, Bergstralh EJ, et al. A randomised trial of high dose compared with low dose omega-3 fatty acids in severe IgA nephropathy[J]. J Am Soc Nephrol, 2001, 12(4): 791-799.
23.	Dillon JJ. Fish oil therapy for IgA nephropathy. Efficacy and interstudy variability[J]. J Am Soc Nephrol, 1997, 8(11): 1739-1744.
24.	Nowack R, Birck R, Van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy[J]. The Lancet, 1997, 349(9054): 774.
25.	Frisch G, Lin J L, Rosenstock J, et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial[J]. Nephrol Dial Transplant, 2005, 20(10): 2139-2145.
26.	Tang S, Leung JC, Chan LY, et al. Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy[J]. Kidney Int, 2005, 68(2): 802-812.
27.	王伟铭. KDIGO关于原发性肾小球肾炎的治疗初步意见[J]. 中国医学前沿杂志, 2011, 3(2): 18-21.
28.	Briggs WA, Choi MJ, Scheel PJ Jr. Successful mycophenolate mofetil treatment of glomerular disease[J]. Am J Kidney Dis, l998, 31(2): 2l3-217.
29.	Borrows R, Chusney G, James A, et al. Determinants of mycophenolic acid levels after renal transplantation[J]. Ther Drug Monit, 2005, 27(4): 442-450.
30.	Staatz CE, Tett SE, Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J]. Clin Pharmacokinet, 2007, 46(1): 13-58.
31.	Hesselink DA, van Hest RM, Mathot R, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein2[J]. Am J Transplant, 2005, 5(5): 987-994.
32.	Lightstone L. Lupus nephritis: where are we now?[J]. Curr Opin Rheumatol, 2010, 22(3): 252-256.
33.	Yu ZC, Zhou PJ, Xu D, et al. Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal transplant patients[J]. Brit J Clin Pharmaco, 2006, 62(4): 446-452.
34.	Zhou PJ, Xu D, Yu ZC, et al. Pharmacokinetics of mycophenolic acid and estimation of exposure using multiple linear regression equations in Chinese renal allograft recipients[J]. Clin Pharmacokinet, 2007, 46(5): 389-401.
35.	Lu XY, Huang HF, Sheng TJ, et al. Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients[J]. J Zhejiang Univ Sci B, 2005, 6 (9): 885-891.
36.	Zheng CX, Liu ZH, Qin WS, et al. Moitoring of mycophenolic acid concentration for mycophenolate mofetil treatment in patients with glomerular diseases[J]. Chin Nephrol Dial Transplant, 2007, 16(5): 406-412.
37.	Van Gelder T, Hilbrands LB, Vanrenterghem Y, et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation[J]. Transplantation, 1999, 68(2): 261-266.

1. 　Luetscher Jr JA, Deming QB, Harvey J, et al. Treatment of nephrosis with cortisone[J]. J Clin Invest, 1950, 29(12): 1576-1587.
2. 　Vanderwoude FJ. Mycophenplate mofetil(RS 61443): nothing new under the sun or an important break-through in the field of transplantation? [J]. Nephrol Dial Transpl, 1995, 10(7): 1112-1115.
3. 　Huang YF, Liu ZH, Huang HD, et al. Effects of mycophenolic acid on endothelial cells[J]. Int Immunopharmacol, 2005, 5(6): 1029-1039.
4. 　Allison AC. Mechanisms of action of mycophenolate mofetil[J]. Lupus, 2005, 14(3): S2-S8.
5. 　Apple GB, Radhakrishnan J, Ginzler EM. Use of mycophenolate mofetil in autoimmune and renal diseases[J]. Transplantation, 2005, 80(2): S265-S271.
6. 　Mase BD, Oyen R, Claes K, et al. Mycophenolate mofetil in IgA nephropathy: Results of a 3-year prospective placebo-controlled randomized study[J]. Kidney Int, 2004, 65(5): 1842-1849.
7. 　Trinidad PR, Meza L, Diaz OA. Mycophenolate mofetil treatment in primary glomerular diseases without response to conventional immunosuppressive agents[J]. J Am Soc Nephrol, 2003, 14(7): 800-812.
8. 　Polenakovic M, Grcevska L, Dzikova S. Mycophenolate mofetil in treatment of idiopathic stages IIII-V membranous nephropathy[J]. Nephrol Dial Transpl, 2003, 18(6): 1233-1234.
9. 　D’Amcio G. Natural history of idiopathic IgA nephropathy: the role of clinical and histological prognostic factors[J]. Am J Kidney Dis, 2002, 36(2): 227-37.
10. 　Tang S, Tang A, Wong S, et al. Long–term study of mycophenolate mofetil treatment in IgA nephropathy[J]. Kidney Int, 2010, 77(6): 543-549.
11. 　Groth C, Pichlmayr R, Sadek S, et al. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection[J]. Lancet, 1995, 345(8961): 1321-1325.
12. 　Appel GB, Contreras G, Dooley MA, et al. mycophenolate mofetil versus cyclophosphamide for Induction Treatment of Lupus Nephritis[J]. J Am Soc Nephrol, 2009, 20(5): 1103-1112.
13. 　陈香美, 陈仆, 蔡广研, 等. 麦考酚酸酯治疗IgA 肾病的随访对照观察[J]. 中华医学杂志, 2006, 82(12): 796-891.
14. 　Donadio J, Grande J. IgA nephropathy[J]. N Engl J Med, 2002, 347(10): 738-748.
15. 　Galla JH. IgA nephropathy[J]. Kidney Int, 1995, 47(2): 377-387.
16. 　Zatz R, Noronha IL, Fujihara CK. Experimental and clinical rationale for use of MMF in nontransplant progressive nephropathies[J]. Am J Physiol Renal Physiol, 2002, 283(6): 1167-1175.
17. 　Russo D, Pisani A, Balletta MM, et al. Additive antiproteinuric effect of converting enzyme inhibitor and Losartan in normotensive patients with IgA nephropathy[J]. Am J Kidney Dis, 1999, 33(5): 851-856.
18. 　Samuels JA, Strippoli G FM, Craig J C, et al. Immunosuppressive agents for treating IGA nephropathy(Cochrane Review)[J]. Cochrane Database Syst Rev, 2003, (4): CD003965.
19. 　Bennett WM, Walke RG, Kincaid-Smith P. Treatment of IgA nephropathy with eicosapentanoic acid: A two-year prospective trial[J]. Clin Nephrol, 1989, 31(3): 128-131.
20. 　Pettersson EE, Rekola S, Berglund L, et al. Treatment of IgA nephropathy with omega-3 polysaturated fatty acids: a prospective, double-blind, randomised study[J]. Clin Nephrol, 1994, 41(4): 183-190.
21. 　Donadio JV Jr, Bergstralh EF, Offord KP, et al. A controlled trial of fish oil in IgA nephropathy[J]. N Engl J Med, 1994, 331(18): 1194-1199.
22. 　Donadio JV Jr, Larson TS, Bergstralh EJ, et al. A randomised trial of high dose compared with low dose omega-3 fatty acids in severe IgA nephropathy[J]. J Am Soc Nephrol, 2001, 12(4): 791-799.
23. 　Dillon JJ. Fish oil therapy for IgA nephropathy. Efficacy and interstudy variability[J]. J Am Soc Nephrol, 1997, 8(11): 1739-1744.
24. 　Nowack R, Birck R, Van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy[J]. The Lancet, 1997, 349(9054): 774.
25. 　Frisch G, Lin J L, Rosenstock J, et al. Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial[J]. Nephrol Dial Transplant, 2005, 20(10): 2139-2145.
26. 　Tang S, Leung JC, Chan LY, et al. Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy[J]. Kidney Int, 2005, 68(2): 802-812.
27. 　王伟铭. KDIGO关于原发性肾小球肾炎的治疗初步意见[J]. 中国医学前沿杂志, 2011, 3(2): 18-21.
28. 　Briggs WA, Choi MJ, Scheel PJ Jr. Successful mycophenolate mofetil treatment of glomerular disease[J]. Am J Kidney Dis, l998, 31(2): 2l3-217.
29. 　Borrows R, Chusney G, James A, et al. Determinants of mycophenolic acid levels after renal transplantation[J]. Ther Drug Monit, 2005, 27(4): 442-450.
30. 　Staatz CE, Tett SE, Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J]. Clin Pharmacokinet, 2007, 46(1): 13-58.
31. 　Hesselink DA, van Hest RM, Mathot R, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein2[J]. Am J Transplant, 2005, 5(5): 987-994.
32. 　Lightstone L. Lupus nephritis: where are we now?[J]. Curr Opin Rheumatol, 2010, 22(3): 252-256.
33. 　Yu ZC, Zhou PJ, Xu D, et al. Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal transplant patients[J]. Brit J Clin Pharmaco, 2006, 62(4): 446-452.
34. 　Zhou PJ, Xu D, Yu ZC, et al. Pharmacokinetics of mycophenolic acid and estimation of exposure using multiple linear regression equations in Chinese renal allograft recipients[J]. Clin Pharmacokinet, 2007, 46(5): 389-401.
35. 　Lu XY, Huang HF, Sheng TJ, et al. Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients[J]. J Zhejiang Univ Sci B, 2005, 6 (9): 885-891.
36. 　Zheng CX, Liu ZH, Qin WS, et al. Moitoring of mycophenolic acid concentration for mycophenolate mofetil treatment in patients with glomerular diseases[J]. Chin Nephrol Dial Transplant, 2007, 16(5): 406-412.
37. 　Van Gelder T, Hilbrands LB, Vanrenterghem Y, et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation[J]. Transplantation, 1999, 68(2): 261-266.

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小剂量霉酚酸酯联合激素治疗IgA肾病临床观察

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