• 成都中醫(yī)藥大學(xué)臨床醫(yī)學(xué)院（成都，610072）;

【摘要】狼瘡腎炎（lupus nephritis，LN）是影響系統(tǒng)性紅斑狼瘡患者遠(yuǎn)期預(yù)后的主要因素之一。本文回顧性地探討了近五年國(guó)內(nèi)外LN的病理研究進(jìn)展，包括發(fā)病機(jī)制和分型研究。同時(shí)，文章也討論了各種治療方案和新興藥物劑型。盡管LN的治療已取得了許多進(jìn)步，但仍然存在很多困難，需要進(jìn)一步的研究。

引用本文： 方明,艾儒棣. 狼瘡腎炎的臨床研究進(jìn)展. 華西醫(yī)學(xué), 2010, 25(7): 1377-1381. doi: 復(fù)制

1. Singh S, Saxena R. Lupus nephritis[J]. American Journal of Medical Science, 2009, 337(6): 451-460.
2. Tang S, Liu S, Lai K. Pathogenesis of lupus nephritis: an update[J]. Nephrology, 2005, 10(2): 174-179.
3. Waldman M, Madaio M. Pathogenic autoantibodies in lupus nephritis[J]. Lupus, 2005, 14(1): 19-24.
4. Kubota T, Watanabe N, Kanai Y, et al. Enhancement of oxidative cleavage of DNA by the binding sties of two anti-double-stranded DNA antibodies[J]. Journal of Biological Chemistry, 1996, 271: 6555-6561.
5. Morel L, Rudofsky U, Longmate J, et al. Polygenic control of susceptibility to murine systemic lupus erythematosus[J]. Immunity, 1994, 1: 219-229.  [6]Lauwerys B, Wakeland E. Genetics of lupus nephritis[J]. Lupus, 2005, 14: 2-12.
6. Najafi C, Korbet S, Lewis E, et al. Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis[J]. Kidney International, 2001, 59: 2156-2163.
7. Lewis E, Schwartz M. Pathology of lupus nephritis[J]. Lupus, 2005, 14: 31-38.
8. Houssiau F, Ginzler E. Current treatment of lupus nephritis[J]. Lupus, 2008, 17: 426-430.
9. Houssiau F, Vasconcelos C, D’Cruz D. Immunosupressive therapy in lupus nephritis. The Euro-lupus nephritis trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide[J]. Arthritis Rheumatology, 2002, 46: 2121-2131.
10. Houssiau F, Vasconcelos C, D’Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide[J]. Ann Rheum Dis, 2010, 69(1): 61-64.
11. Lee YH, Woo JH, Choi SJ, et al. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis[J]. Lupus. 2010, 19(6): 703-710.
12. Mak A, Cheak A, Tan J, et al. Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression[J]. Rheumatology(Oxford), 2009, 48(8): 944-952.
13. Lu F, Tu Y, Peng X, et al. A prospective multicentre study of mycophenolate mofetil combined with prednisonlone as induction therapy in 213 patients with active lupus nephritis[J]. Lupus, 2008, 17: 622-629.
14. Paydas S, Kurt C, Taskapan C, et al. The effect of mycophenolate mofetil on primary and secondary treatment of primary glomerulonephritis and lupus nephritis[J]. Int Urol Nephrol, 2009, 41: 145-152.
15. Elyan M, Ballou S. The effectiveness and safety of mycophenolate mofetil in lupus nephritis[J]. Clin Rheumatol, 2009, 28: 835-840.
16. Appel G, Contreras B, Dooley G. et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis[J]. J Am Soc Nephrol, 2009, 20: 1103-1112.
17. Tang Z, Yang G, Yu C. Effects of mycophenolate mofetil for patients with crescentic lupus nephritis[J]. Nephrology(Carlton), 2008, 13: 702-707.
18. Lau K, Ault K, Jones D, et al. Induction therapy for pediatric focal proliferative lupus nephritis: cyclophosphamide versus mycophenolate mofetil[J]. J Pediatr Health Care, 2008, 22: 282-288.
19. Kasitanon N, Petri M, Haas M, et al. Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases[J]. Lupus, 2008, 17: 40-45.
20. Wang J, Hu W, Xie H, et al. Induction therapies for class Ⅳ lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide[J]. Lupus, 2007, 16: 707-712.
21. Flores-Suarez L. Remission of severe relapsing or persistent lupus nephritis using mycophenolate mofetil[J]. Arch Med Res, 2006, 37: 68-73.
22. Ginzler E, Aranow C. Mycophenolate mofetil in lupus nephritis[J]. Lupus, 2005, 14(1): 59-64.
23. Ong L, Hooi M, Lim L, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis[J]. Nephrology(Carlton), 2008, 10: 504-510.
24. Cross J, Dwomoa A, Andrews P, Mycophenolate mofetil for remission induction in severe lupus nephritis[J]. Nephron Clin Pract, 2005, 100: 92-100.
25. Kapitsinou P, Boletis J, Skopouli F, et al. Lupus nephritis: treatment with mycophenolate mofetil[J]. Rheumatology(Oxford), 2004, 43: 377-380.
26. Chan T, Li M, Tang F, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis[J]. N Engl J Med, 2000, 343: 1156-1162.
27. Bao H, Liu Z, Xie H, Successful treatment of class V+Ⅳ lupus nephritis with multitarget therapy[J]. J Am Soc Nephrol, 2008, 19(10): 2001-2010.
28. Lightstone L. Lupus nephritis: where are we now?[J]. Curr Opin Rheumatol. 2010, 22(3): 252-256.
29. Pepper R, Griffith M, Kirwan C. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids[J]. Nephrol Dial Transplant, 2009, 24(12): 3717-3723.
30. Ramos-Casalas M, Soto M, Cuadrado M, et al. Rituximab in systemic lupus erythematosus: A systematic review of off-label use in 188 cases[J]. Lupus, 2009, 18: 767-776.
31. Li E, Tam L, Zhu T, et al. Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?[J]Rheumatology(Oxford), 2009, 48(8): 892-898.
32. Perfumo F, Martini A. Lupus nephritis in children[J]. Lupus, 2005, 14(1): 83-88.
33. Wong S, Tse K, Lee T. Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong[J]. Pediatr Nephrol, 2006, 21: 1104-1112.
34. Opastirakul S, Chartapisak W. Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy[J]. Pediatr Nephrol, 2005, 20: 1750-1755.
35. Laoprasopwattana K, Dissaneewate P, Vachvanichsanong P. Fatal infection in children with lupus nephritis treated with intravenous cyclophosphamide[J]. Pediatr Nephrol, 2009, 24: 1334-1343.
36. Ranchin B, Fargue S, New treatment strategies for proliferative lupus nephritis: keep children in mind![J]. Lupus, 2007, 16: 684-691.
37. Brunner H, Bishnoi A, Barron A, et al. Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus[J]. Lupus, 2006, 15: 198-206.
38. Baskin E, Ozen S, Cakar N. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis[J]. Pediatr Nephrol, 2010, 25(1): 111-117.
  1. 1. Singh S, Saxena R. Lupus nephritis[J]. American Journal of Medical Science, 2009, 337(6): 451-460.
  2. 2. Tang S, Liu S, Lai K. Pathogenesis of lupus nephritis: an update[J]. Nephrology, 2005, 10(2): 174-179.
  3. 3. Waldman M, Madaio M. Pathogenic autoantibodies in lupus nephritis[J]. Lupus, 2005, 14(1): 19-24.
  4. 4. Kubota T, Watanabe N, Kanai Y, et al. Enhancement of oxidative cleavage of DNA by the binding sties of two anti-double-stranded DNA antibodies[J]. Journal of Biological Chemistry, 1996, 271: 6555-6561.
  5. 5. Morel L, Rudofsky U, Longmate J, et al. Polygenic control of susceptibility to murine systemic lupus erythematosus[J]. Immunity, 1994, 1: 219-229.  [6]Lauwerys B, Wakeland E. Genetics of lupus nephritis[J]. Lupus, 2005, 14: 2-12.
  6. 6. Najafi C, Korbet S, Lewis E, et al. Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis[J]. Kidney International, 2001, 59: 2156-2163.
  7. 7. Lewis E, Schwartz M. Pathology of lupus nephritis[J]. Lupus, 2005, 14: 31-38.
  8. 8. Houssiau F, Ginzler E. Current treatment of lupus nephritis[J]. Lupus, 2008, 17: 426-430.
  9. 9. Houssiau F, Vasconcelos C, D’Cruz D. Immunosupressive therapy in lupus nephritis. The Euro-lupus nephritis trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide[J]. Arthritis Rheumatology, 2002, 46: 2121-2131.
  10. 10. Houssiau F, Vasconcelos C, D’Cruz D, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide[J]. Ann Rheum Dis, 2010, 69(1): 61-64.
  11. 11. Lee YH, Woo JH, Choi SJ, et al. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis[J]. Lupus. 2010, 19(6): 703-710.
  12. 12. Mak A, Cheak A, Tan J, et al. Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression[J]. Rheumatology(Oxford), 2009, 48(8): 944-952.
  13. 13. Lu F, Tu Y, Peng X, et al. A prospective multicentre study of mycophenolate mofetil combined with prednisonlone as induction therapy in 213 patients with active lupus nephritis[J]. Lupus, 2008, 17: 622-629.
  14. 14. Paydas S, Kurt C, Taskapan C, et al. The effect of mycophenolate mofetil on primary and secondary treatment of primary glomerulonephritis and lupus nephritis[J]. Int Urol Nephrol, 2009, 41: 145-152.
  15. 15. Elyan M, Ballou S. The effectiveness and safety of mycophenolate mofetil in lupus nephritis[J]. Clin Rheumatol, 2009, 28: 835-840.
  16. 16. Appel G, Contreras B, Dooley G. et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis[J]. J Am Soc Nephrol, 2009, 20: 1103-1112.
  17. 17. Tang Z, Yang G, Yu C. Effects of mycophenolate mofetil for patients with crescentic lupus nephritis[J]. Nephrology(Carlton), 2008, 13: 702-707.
  18. 18. Lau K, Ault K, Jones D, et al. Induction therapy for pediatric focal proliferative lupus nephritis: cyclophosphamide versus mycophenolate mofetil[J]. J Pediatr Health Care, 2008, 22: 282-288.
  19. 19. Kasitanon N, Petri M, Haas M, et al. Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases[J]. Lupus, 2008, 17: 40-45.
  20. 20. Wang J, Hu W, Xie H, et al. Induction therapies for class Ⅳ lupus nephritis with non-inflammatory necrotizing vasculopathy: mycophenolate mofetil or intravenous cyclophosphamide[J]. Lupus, 2007, 16: 707-712.
  21. 21. Flores-Suarez L. Remission of severe relapsing or persistent lupus nephritis using mycophenolate mofetil[J]. Arch Med Res, 2006, 37: 68-73.
  22. 22. Ginzler E, Aranow C. Mycophenolate mofetil in lupus nephritis[J]. Lupus, 2005, 14(1): 59-64.
  23. 23. Ong L, Hooi M, Lim L, et al. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis[J]. Nephrology(Carlton), 2008, 10: 504-510.
  24. 24. Cross J, Dwomoa A, Andrews P, Mycophenolate mofetil for remission induction in severe lupus nephritis[J]. Nephron Clin Pract, 2005, 100: 92-100.
  25. 25. Kapitsinou P, Boletis J, Skopouli F, et al. Lupus nephritis: treatment with mycophenolate mofetil[J]. Rheumatology(Oxford), 2004, 43: 377-380.
  26. 26. Chan T, Li M, Tang F, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis[J]. N Engl J Med, 2000, 343: 1156-1162.
  27. 27. Bao H, Liu Z, Xie H, Successful treatment of class V+Ⅳ lupus nephritis with multitarget therapy[J]. J Am Soc Nephrol, 2008, 19(10): 2001-2010.
  28. 28. Lightstone L. Lupus nephritis: where are we now?[J]. Curr Opin Rheumatol. 2010, 22(3): 252-256.
  29. 29. Pepper R, Griffith M, Kirwan C. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids[J]. Nephrol Dial Transplant, 2009, 24(12): 3717-3723.
  30. 30. Ramos-Casalas M, Soto M, Cuadrado M, et al. Rituximab in systemic lupus erythematosus: A systematic review of off-label use in 188 cases[J]. Lupus, 2009, 18: 767-776.
  31. 31. Li E, Tam L, Zhu T, et al. Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis?[J]Rheumatology(Oxford), 2009, 48(8): 892-898.
  32. 32. Perfumo F, Martini A. Lupus nephritis in children[J]. Lupus, 2005, 14(1): 83-88.
  33. 33. Wong S, Tse K, Lee T. Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong[J]. Pediatr Nephrol, 2006, 21: 1104-1112.
  34. 34. Opastirakul S, Chartapisak W. Infection in children with lupus nephritis receiving pulse and oral cyclophosphamide therapy[J]. Pediatr Nephrol, 2005, 20: 1750-1755.
  35. 35. Laoprasopwattana K, Dissaneewate P, Vachvanichsanong P. Fatal infection in children with lupus nephritis treated with intravenous cyclophosphamide[J]. Pediatr Nephrol, 2009, 24: 1334-1343.
  36. 36. Ranchin B, Fargue S, New treatment strategies for proliferative lupus nephritis: keep children in mind![J]. Lupus, 2007, 16: 684-691.
  37. 37. Brunner H, Bishnoi A, Barron A, et al. Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus[J]. Lupus, 2006, 15: 198-206.
  38. 38. Baskin E, Ozen S, Cakar N. The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis[J]. Pediatr Nephrol, 2010, 25(1): 111-117.