The aim is to systematically review the treatment for lupus nephritis (LN) by performing an overview of systematic reviews and meta-analyses. Electronic databases of OVID MEDLINE, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses investigating treatments for LN up to 13 July 2016. A measurement tool to assess systematic reviews (AMSTAR) was used to assess the quality of included studies. Totally, 24 studies were included. Of the eligible studies, 3 studies were rated as poor quality, 11 as moderate, and 10 as good. In LN induction therapy, comparing to cyclophosphamide, tacrolimus had higher complete remission rate, response rate, and anti-dsDNA negative conversion rate and led to lower risks of gastrointestinal symptoms and amenorrhea, and mycophenolate mofetil (MMF) was associated with higher response rate and less adverse events of leucopenia, alopecia, and ovarian failure. However, there was no difference in the efficacy and adverse events between tacrolimus and MMF. In LN maintenance therapy, the relapse rate and leucopenia rate were lower in MMF group than in azathioprine group, but there were no differences of end-stage kidney disease rate and mortality rate between the two groups. For LN induction therapy, both Tacrolimus and MMF are more effective and safer than cyclophosphamide, while there are no differences of efficacy or safety between the two treatments. For LN maintenance therapy, MMF seems to have less adverse events and lower relapse rate than azathioprine.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Maroz N, Segal MS (2013) Lupus nephritis and end-stage kidney disease. Am J Med Sci 346(4):319–323. doi:10.1097/MAJ.0b013e31827f4ee3
Ward MM (2000) Changes in the incidence of end-stage renal disease due to lupus nephritis, 1982–1995. Arch Intern Med 160(20):3136–3140
Okpechi IG, Gcelu A, Ameh OI (2015) Lupus nephritis: a simplified approach to diagnosis and treatment in South Africa. S Afr Med J 105(12):1071. doi:10.7196/SAMJ.2015.v105i12.10224
Tang Y, Zhang X, Ji L, Mi X, Liu F, Yang L, Qin W (2015) Clinicopathological and outcome analysis of adult lupus nephritis patients in China. Int Urol Nephrol 47(3):513–520. doi:10.1007/s11255-014-0903-y
Hanly JG, O’Keeffe AG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, Bae SC, Bernatsky S, Clarke AE, Wallace DJ, Merrill JT, Isenberg DA, Rahman A, Ginzler EM, Fortin P, Gladman DD, Sanchez-Guerrero J, Petri M, Bruce IN, Dooley MA, Ramsey-Goldman R, Aranow C, Alarcon GS, Fessler BJ, Steinsson K, Nived O, Sturfelt GK, Manzi S, Khamashta MA, van Vollenhoven RF, Zoma AA, Ramos-Casals M, Ruiz-Irastorza G, Lim SS, Stoll T, Inanc M, Kalunian KC, Kamen DL, Maddison P, Peschken CA, Jacobsen S, Askanase A, Theriault C, Thompson K, Farewell V (2016) The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford, England) 55(2):252–262
Cameron JS (1999) Lupus nephritis. J Am Soc Nephrol 10(2):413–424
Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Mejía JC, Aydintug AO, Chwalinska-Sadowska H, de Ramón E, Fernández-Nebro A, Galeazzi M, Valen M, Mathieu A, Houssiau F, Caro N, Alba P, Ramos-Casals M, Ingelmo M, Hughes GRV (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period. Medicine 82(5):299–308. doi:10.1097/01.md.0000091181.93122.55
Imran TF, Yick F, Verma S, Estiverne C, Ogbonnaya-Odor C, Thiruvarudsothy S, Reddi AS, Kothari N (2016) Lupus nephritis: an update. Clin Exp Nephrol 20(1):1–13. doi:10.1007/s10157-015-1179-y
Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, Boletis J, Cervera R, Dorner T, Doria A, Ferrario F, Floege J, Houssiau FA, Ioannidis JP, Isenberg DA, Kallenberg CG, Lightstone L, Marks SD, Martini A, Moroni G, Neumann I, Praga M, Schneider M, Starra A, Tesar V, Vasconcelos C, van Vollenhoven RF, Zakharova H, Haubitz M, Gordon C, Jayne D, Boumpas DT (2012) Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 71(11):1771–1782. doi:10.1136/annrheumdis-2012-201940
Chan TM (2015) Treatment of severe lupus nephritis: the new horizon. Nat rev Nephrol 11(1):46–61. doi:10.1038/nrneph.2014.215
Shea BJ, Bouter LM, Peterson J, Boers M, Andersson N, Ortiz Z, Ramsay T, Bai A, Shukla VK, Grimshaw JM (2007) External validation of a measurement tool to assess systematic reviews (AMSTAR). PLoS One 2(12):e1350. doi:10.1371/journal.pone.0001350
Austin JH, Bentley LE, Kolanczyk DM, Patel NP (2013) Refractory proliferative lupus nephritis: an evidence-based review of pharmacotherapy. J Pharm Technol 29(6):265–282
Bansal VK, Beto JA (1997) Treatment of lupus nephritis: a meta-analysis of clinical trials. Am J Kidney Dis 29(2):193–199
Cao H, Rao Y, Liu L, Lin J, Yang H, Zhang X, Chen Z (2015) The efficacy and safety of leflunomide for the treatment of lupus nephritis in chinese patients: systematic review and meta-analysis. PLoS One 10(12):e0144548. doi:10.1371/journal.pone.0144548
Deng J, Huo D, Wu Q, Yang Z, Liao Y (2012) A meta-analysis of randomized controlled trials comparing tacrolimus with intravenous cyclophosphamide in the induction treatment for lupus nephritis. Tohoku J Exp Med 227(4):281–288
Feng L, Deng J, Huo DM, Wu QY, Liao YH (2013) Mycophenolate mofetil versus azathioprine as maintenance therapy for lupus nephritis: a meta-analysis. Nephrology 18(2):104–110
Flanc RS, Roberts MA, Strippoli GF, Chadban SJ, Kerr PG, Atkins RC (2004) Treatment for lupus nephritis. Cochrane Database Syst Rev 1:CD002922
Hannah J, Casian A, D’Cruz D (2016) Tacrolimus use in lupus nephritis: a systematic review and meta-analysis. Autoimmun Rev 15(1):93–101. doi:10.1016/j.autrev.2015.09.006
Henderson L, Masson P, Craig JC, Flanc RS, Roberts MA, Strippoli GF, Webster AC (2012) Treatment for lupus nephritis. Cochrane Database Syst Rev 12:CD002922
Kamanamool N, McEvoy M, Attia J, Ingsathit A, Ngamjanyaporn P, Thakkinstian A (2010) Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis: systematic review and meta-analysis. Medicine 89(4):227–235
Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 19(6):703–710
Lee YH, Lee HS, Choi SJ, Ji JD, Song GG (2011) Efficacy and safety of tacrolimus therapy for lupus nephritis: a systematic review of clinical trials. Lupus 20(6):636–640
Lee YH, Song GG (2015) Relative efficacy and safety of tacrolimus, mycophenolate mofetil, and cyclophosphamide as induction therapy for lupus nephritis: a Bayesian network meta-analysis of randomized controlled trials. Lupus 24(14):1520–1528
Liu LL, Jiang Y, Wang LN, Yao L, Li ZL (2012) Efficacy and safety of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis: a meta-analysis of randomized controlled trials. Drugs 72(11):1521–1533
Mak A, Cheak AA, Tan JY, Su HC, Ho RC, Lau CS (2009) Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression. Rheumatology 48(8):944–952
Maneiro JR, Lopez-Canoa N, Salgado E, Gomez-Reino JJ (2014) Maintenance therapy of lupus nephritis with mycophenolate or azathioprine: systematic review and meta-analysis. Rheumatology 53(5):834–838
Moore RA, Derry S (2006) Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther 8(6):R182
Swan JT, Riche DM, Riche KD, Majithia V (2011) Systematic review and meta-analysis of immunosuppressant therapy clinical trials in membranous lupus nephritis. J Investig Med 59(2):246–258
Tian SYF, Feldman BM, Beyene J, Brown PE, Uleryk EM, Silverman ED (2014) Immunosuppressive therapies for the induction treatment of proliferative lupus nephritis: a systematic review and network metaanalysis (provisional abstract). Database Abstr Rev Eff 2:1998–2007
Tian SY, Feldman BM, Beyene J, Brown PE, Uleryk EM, Silverman ED (2015) Immunosuppressive therapies for the maintenance therapy of proliferative lupus nephritis: a systematic review and network metaanalysis. J Rheumatol 42(8):1392–1400
Touma Z, Gladman DD, Urowitz MB, Beyene J, Uleryk EM, Shah PS (2011) Mycophenolate mofetil for induction treatment of lupus nephritis: a systematic review and metaanalysis. J Rheumatol 38(1):69–78
Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR (2007) Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol 2(5):968–975
Yang M, Li M, He W, Wang B, Gu Y (2014) Calcineurin inhibitors may be a reasonable alternative to cyclophosphamide in the induction treatment of active lupus nephritis: a systematic review and meta-analysis (provisional abstract). Database Abstr Rev Eff 2:1663–1670
Zhang X, Ji L, Yang L, Tang X, Qin W (2016) The effect of calcineurin inhibitors in the induction and maintenance therapy of lupus nephritis: a systematic review and meta-analysis. Int Urol Nephrol 48(5):731–743. doi:10.1007/s11255-015-1201-z
Zhu B, Chen N, Lin Y, Ren H, Zhang W, Wang W, Pan X, Yu H (2007) Mycophenolate mofetil in induction and maintenance therapy of severe lupus nephritis: a meta-analysis of randomized controlled trials. Nephrol Dial Transpl 22(7):1933–1942. doi:10.1093/ndt/gfm066
Mok CC (2015) Mycophenolate mofetil for lupus nephritis: an update. Expert Rev Clin Immunol 11(12):1353–1364. doi:10.1586/1744666X.2015.1087314
Baweja S, Wiggins K, Lee D, Blair S, Fraenkel M, McMahon LP (2011) Benefits and limitations of plasmapheresis in renal diseases: an evidence-based approach. J Artif Organs 14(1):9–22. doi:10.1007/s10047-010-0529-5
Punaro MG (2013) The treatment of systemic lupus proliferative nephritis. Pediatr Nephrol 28(11):2069–2078. doi:10.1007/s00467-012-2327-1
Yuehong Chen is funded by China Scholarship Council (Grant Number 201606240021). We do not have any other conflicts of interests to disclose.
Human and animal rights statement
This article does not contain any studies with human participants or animals performed by any of the authors.
About this article
Cite this article
Chen, Y., Sun, J., Zou, K. et al. Treatment for lupus nephritis: an overview of systematic reviews and meta-analyses. Rheumatol Int 37, 1089–1099 (2017). https://doi.org/10.1007/s00296-017-3733-2
- Lupus nephritis
- Mycophenolate mofetil
- Systematic review