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  • Review Article
  • Published:

Towards new avenues in the management of lupus glomerulonephritis

Nature Reviews Rheumatology volume 12, pages 221–234 (2016)Cite this article

Subjects

Key Points

  • New therapeutic regimens with reduced toxicity are now available for lupus nephritis

  • Mycophenolate mofetil is the preferred first-line treatment for lupus nephritis, although it is not superior to cyclophosphamide and long-term data are lacking

  • Tacrolimus has equal efficacy to mycophenolate mofetil or cyclophosphamide as induction therapy, although evidence is currently limited to 6 months

  • Biological agents such as rituximab have shown promise in refractory lupus nephritis; controlled trials of rituximab (without high-dose glucocorticoids) as induction therapy and for refractory disease are in progress

  • Novel serum and urinary biomarkers are being validated to aid in diagnosis, early detection of flare, and prognostic stratification in lupus nephritis

  • Treatment of lupus nephritis has to be individualized, taking into account interethnic variation in the efficacy and tolerability of the available regimens

Abstract

Renal involvement in systemic lupus erythematosus (SLE) carries substantial morbidity and mortality. Conventional immunosuppressive agents (cyclophosphamide and azathioprine) have suboptimal efficacy and substantial toxicity. Mycophenolate mofetil has emerged as an alternative agent for both induction and maintenance therapy in lupus nephritis because of its reduced gonadal toxicity, despite its failure to demonstrate superiority over cyclophosphamide in pivotal studies. The calcineurin inhibitor tacrolimus has equivalent efficacy to cyclophosphamide and mycophenolate mofetil for inducing remission of lupus nephritis. Although rituximab has shown promise in refractory lupus nephritis, combining rituximab with mycophenolate mofetil as initial therapy offers no additional benefit. Considerable interethnic variation is evident in the efficacy and tolerability of the various immunosuppressive regimens, which necessitates individualized treatment and comparison of the efficacy of new regimens across different ethnic groups. For example, low-dose combinations of tacrolimus and mycophenolate mofetil seem to be more effective than pulse cyclophosphamide as induction therapy in Chinese patients. The same regimen has also been used successfully to treat refractory proliferative and membranous lupus nephritis in patients of various ethnic groups. Finally, novel serum and urinary biomarkers are being validated for diagnosis, prognostic stratification and early recognition of flares in lupus nephritis.

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Figure 1: Lupus nephritis is a highly heterogeneous disease.
Figure 2: Biomarkers for lupus nephritis.
Figure 3: Selection of induction and maintenance therapy for patients with severe proliferative lupus nephritis.

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References

  1. Mok, C. C. Understanding lupus nephritis: diagnosis, management, and treatment options. Int. J. Womens Health 4, 213–222 (2012).

    PubMed  PubMed Central  Google Scholar 

  2. Mok, C. C., Wong, R. W. & Lau, C. S. Lupus nephritis in Southern Chinese patients: clinicopathologic findings and long-term outcome. Am. J. Kidney Dis. 34, 315–323 (1999).

    CAS  PubMed  Google Scholar 

  3. Mok, C. C. et al. Long-term outcome of diffuse proliferative lupus glomerulonephritis treated with cyclophosphamide. Am. J. Med. 119, 355.e25–333.e33 (2006).

    Google Scholar 

  4. Korbet, S. M., Schwartz, M. M., Evans, J. & Lewis, E. J. Severe lupus nephritis: racial differences in presentation and outcome. J. Am. Soc. Nephrol. 18, 244–254 (2007).

    PubMed  Google Scholar 

  5. Hui, M. et al. Lupus nephritis: a 15-year multi-centre experience in the UK. Lupus 22, 328–332 (2013).

    CAS  PubMed  Google Scholar 

  6. Mok, C. C., Kwok, R. C. & Yip, P. S. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 65, 2154–2160 (2013).

    CAS  PubMed  Google Scholar 

  7. Fernández, M. et al. A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE. Arthritis Rheum. 57, 576–584 (2007).

    PubMed  Google Scholar 

  8. Sánchez, E. et al. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations. Arthritis Rheum. 64, 3687–3694 (2012).

    PubMed  PubMed Central  Google Scholar 

  9. Hiraki, L. T. et al. Ethnic differences in pediatric systemic lupus erythematosus. J. Rheumatol. 36, 2539–2546 (2009).

    PubMed  Google Scholar 

  10. Mok, C. C., Tang, S. S., To, C. H. & Petri, M. Incidence and risk factors of thromboembolism in systemic lupus erythematosus: a comparison of three ethnic groups. Arthritis Rheum. 52, 2774–2782 (2005).

    PubMed  Google Scholar 

  11. Costenbader, K. H. et al. Trends in the incidence, demographics, and outcomes of end-stage renal disease due to lupus nephritis in the US from 1995 to 2006. Arthritis Rheum. 63, 1681–1688 (2011).

    PubMed  PubMed Central  Google Scholar 

  12. Cottone, S. et al. Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J. Nephrol. 21, 175–179 (2008).

    PubMed  Google Scholar 

  13. Mok, C. C. et al. Risk and predictors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis: a comparative study. Med. (Baltimore) 86, 203–209 (2007).

    Google Scholar 

  14. Appenzeller, S. et al. The relationship between renal activity and quality of life in systemic lupus erythematosus. J. Rheumatol. 36, 947–952 (2009).

    PubMed  Google Scholar 

  15. Mok, C. C., Cheung, M. Y., Ho, L. Y., Yu, K. L. & To, C. H. Risk and predictors of work disability in Chinese patients with systemic lupus erythematosus. Lupus 17, 1103–1107 (2008).

    CAS  PubMed  Google Scholar 

  16. Felson, D. T. & 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. 311, 1528–1533 (1984).

    CAS  PubMed  Google Scholar 

  17. Austin, H. A. 3rd et al. Therapy of lupus nephritis. N. Engl. J. Med. 314, 614–619 (1986).

    PubMed  Google Scholar 

  18. Arends, S. et al. Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis. Ann. Rheum. Dis. 71, 966–973 (2012).

    CAS  PubMed  Google Scholar 

  19. Houssiau, F. A. et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 46, 2121–2131 (2002).

    CAS  PubMed  Google Scholar 

  20. Houssiau, F. A. et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann. Rheum. Dis. 69, 61–64 (2010).

    CAS  PubMed  Google Scholar 

  21. Mysler, E. F. et al. Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, Phase III study. Arthritis Rheum. 65, 2368–2379 (2013).

    CAS  PubMed  Google Scholar 

  22. ACCESS Trial Group. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol. 66, 3096–3104 (2014).

  23. Hahn, B. H. et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. (Hoboken) 64, 797–808 (2012).

    Google Scholar 

  24. Bertsias, G. K. et al. 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, 1771–1782 (2012).

    CAS  PubMed  Google Scholar 

  25. Tang, Z. et al. Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis. Rheumatol. Int. 30, 45–49 (2009).

    CAS  PubMed  Google Scholar 

  26. Chan, T. M. et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. N. Engl. J. Med. 343, 1156–1162 (2000).

    CAS  PubMed  Google Scholar 

  27. Ginzler, E. M. et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N. Engl. J. Med. 353, 2219–2228 (2005).

    CAS  PubMed  Google Scholar 

  28. Appel, G. B. et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J. Am. Soc. Nephrol. 20, 1103–1112 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Radhakrishnan, J. et al. Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int. 77, 152–160 (2010).

    CAS  PubMed  Google Scholar 

  30. Isenberg, D. et al. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatol. (Oxford) 49, 128–140 (2010).

    Google Scholar 

  31. Mok, C. C. et al. Overview of lupus nephritis management guidelines and perspective from Asia. Nephrol. (Carlton) 19, 11–20 (2014).

    Google Scholar 

  32. Tang, Z. et al. Effects of mycophenolate mofetil for patients with crescentic lupus nephritis. Nephrol. (Carlton) 13, 702–707 (2008).

    CAS  Google Scholar 

  33. Rovin, B. H. et al. Lupus nephritis: induction therapy in severe lupus nephritis — should MMF be considered the drug of choice? Clin. J. Am. Soc. Nephrol. 8, 147–153 (2013).

    PubMed  Google Scholar 

  34. Scott, L. J., McKeage, K., Keam, S. J. & Plosker, G. L. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs 63, 1247–1297 (2003).

    CAS  PubMed  Google Scholar 

  35. Ekberg, H. et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N. Engl. J. Med. 357, 2562–2575 (2007).

    CAS  PubMed  Google Scholar 

  36. Krämer, B. K. et al. Efficacy and safety of tacrolimus compared with ciclosporin A in renal transplantation: three-year observational results. Nephrol. Dial. Transplant. 23, 2386–2392 (2008).

    PubMed  Google Scholar 

  37. Silva, H. T. Jr et al. Long-term follow-up of a Phase III clinical trial comparing tacrolimus extended-release/MMF, tacrolimus/MMF, and cyclosporine/MMF in de novo kidney transplant recipients. Transplantation 97, 636–641 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Penninga, L., Møller, C. H., Gustafsson, F., Steinbrüchel, D. A. & Gluud, C. Tacrolimus versus cyclosporine as primary immunosuppression after heart transplantation: systematic review with meta-analyses and trial sequential analyses of randomised trials. Eur. J. Clin. Pharmacol. 66, 1177–1187 (2010).

    CAS  PubMed  Google Scholar 

  39. O'Keefe, S. J., Tamura, J., Kincaid, R. L., Tocci, M. J. & O'Neill, E. A. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 357, 692–694 (1992).

    CAS  PubMed  Google Scholar 

  40. Yoon, K. H. Efficacy and cytokine modulating effects of tacrolimus in systemic lupus erythematosus: a review. J. Biomed. Biotechnol. 2010, 686480 (2010).

    PubMed  PubMed Central  Google Scholar 

  41. Heidt, S. et al. Calcineurin inhibitors affect B cell antibody responses indirectly by interfering with T cell help. Clin. Exp. Immunol. 159, 199–207 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Faul, C. et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat. Med. 14, 931–938 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mok, C. C., Tong, K. H., To, C. H., Siu, Y. P. & Au, T. C. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int. 68, 813–817 (2005).

    CAS  PubMed  Google Scholar 

  44. Szeto, C. C. et al. Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis. Rheumatol. (Oxford) 47, 1678–1681 (2008).

    CAS  Google Scholar 

  45. Chen, W. et al. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: a multicenter randomized clinical trial. Am. J. Kidney Dis. 57, 235–244 (2011).

    CAS  PubMed  Google Scholar 

  46. Li, X. et al. Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol. Dial. Transplant. 27, 1467–1472 (2012).

    CAS  PubMed  Google Scholar 

  47. Mok, C. C. et al. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2014-206456, (2014).

  48. Bao, H. et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J. Am. Soc. Nephrol. 19, 2001–2010 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Liu, Z. et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann. Intern. Med. 162, 18–26 (2015).

    PubMed  Google Scholar 

  50. Mok, C. C., To, C. H., Yu, K. L. & Ho, L. Y. Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study. Lupus 22, 1135–1141 (2013).

    CAS  PubMed  Google Scholar 

  51. Mok, C. C. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat. Rev. Nephrol. 5, 212–220 (2009).

    CAS  PubMed  Google Scholar 

  52. Austin, H. A. 3rd, Illei, G. G., Braun, M. J. & Balow, J. E. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J. Am. Soc. Nephrol. 20, 901–911 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Jónsdóttir, T. et al. Clinical improvements in proliferative versus membranous lupus nephritis following B-cell depletion: pooled data from two cohorts. Rheumatol. (Oxford) 49, 1502–1504 (2010).

    Google Scholar 

  54. Illei, G. G. et al. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term follow-up of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 46, 995–1002 (2002).

    CAS  PubMed  Google Scholar 

  55. Moroni, G. et al. A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years. Clin. J. Am. Soc. Nephrol. 1, 925–932 (2006).

    CAS  PubMed  Google Scholar 

  56. Contreras, G. et al. Sequential therapies for proliferative lupus nephritis. N. Engl. J. Med. 350, 971–980 (2004).

    CAS  PubMed  Google Scholar 

  57. Moroni, G. et al. Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up. Nephrol. Dial. Transplant. 21, 1541–1548 (2006).

    CAS  PubMed  Google Scholar 

  58. Chen, W. et al. Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 21, 944–952 (2012).

    CAS  PubMed  Google Scholar 

  59. Houssiau, F. A. et al. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann. Rheum. Dis. 69, 2083–2089 (2010).

    CAS  PubMed  Google Scholar 

  60. Tamirou, F. et al. Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2014-206897, (2015).

  61. Dooley, M. A. et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N. Engl. J. Med. 365, 1886–1895 (2011).

    CAS  PubMed  Google Scholar 

  62. Mok, C. C. Prognostic factors for lupus nephritis. Lupus 14, 39–44 (2005).

    CAS  PubMed  Google Scholar 

  63. Lenz, O., Waheed, A. A., Baig, A., Pop, A. & Contreras, G. Lupus nephritis: maintenance therapy for lupus nephritis — do we now have a plan? Clin. J. Am. Soc. Nephrol. 8, 162–171 (2013).

    CAS  PubMed  Google Scholar 

  64. Mok, C. C. Emerging biological therapies for systemic lupus erythematosus. Expert Opin. Emerg. Drugs 19, 303–322 (2014).

    CAS  PubMed  Google Scholar 

  65. Rovin, B. H. et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 64, 1215–1226 (2012).

    CAS  PubMed  Google Scholar 

  66. Fernández-Nebro, A. et al. Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study. Lupus 21, 1063–1076 (2012).

    PubMed  Google Scholar 

  67. Ramos-Casals, M., Soto, M. J., Cuadrado, M. J. & Khamashta, M. A. Rituximab in systemic lupus erythematosus: a systematic review of off-label use in 188 cases. Lupus 18, 767–776 (2009).

    CAS  PubMed  Google Scholar 

  68. Weidenbusch, M., Römmele, C., Schröttle, A. & Anders, H. J. Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol. Dial. Transplant. 28, 106–111 (2013).

    CAS  PubMed  Google Scholar 

  69. Díaz-Lagares, C. et al. Efficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: pooled data from European cohorts. Autoimmun. Rev. 11, 357–364 (2012).

    PubMed  Google Scholar 

  70. Terrier, B. et al. Safety and efficacy of rituximab in systemic lupus erythematosus: results from 136 patients from the French AutoImmunity and Rituximab registry. Arthritis Rheum. 62, 2458–2466 (2010).

    CAS  PubMed  Google Scholar 

  71. Rovin, B. H. & Parikh, S. V. Lupus nephritis: the evolving role of novel therapeutics. Am. J. Kidney Dis. 63, 677–690 (2014).

    PubMed  PubMed Central  Google Scholar 

  72. Condon, M. B. et al. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann. Rheum. Dis. 72, 1280–1286 (2013).

    CAS  PubMed  Google Scholar 

  73. US National Library of Medicine. ClinicalTrials.gov[online], (2015).

  74. Reddy, V., Jayne, D., Close, D. & Isenberg, D. B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design. Arthritis Res. Ther. 15, S2 (2013).

    PubMed  PubMed Central  Google Scholar 

  75. Jacobi, A. M. et al. Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a Phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 62, 201–210 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Navarra, S. V. et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, Phase 3 trial. Lancet 377, 721–731 (2011).

    CAS  PubMed  Google Scholar 

  77. Furie, R. et al. A Phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 63, 3918–3930 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Mok, C. C. Belimumab: the first FDA approved biological therapy for systemic lupus erythematosus. Int. J. Clin. Rheumatol. 6, 373–377 (2011).

    CAS  Google Scholar 

  79. Manzi, S. et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two Phase III trials. Ann. Rheum. Dis. 71, 1833–1838 (2012).

    CAS  PubMed  Google Scholar 

  80. van Vollenhoven, R. F. et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann. Rheum. Dis. 71, 1343–1349 (2012).

    CAS  PubMed  Google Scholar 

  81. Dooley, M. A. et al. Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus 22, 63–72 (2013).

    CAS  PubMed  Google Scholar 

  82. US National Library of Medicine. ClinicalTrials.gov[online], (2015).

  83. Stohl, W. Systemic lupus erythematosus and its ABCs (APRIL/BLyS complexes). Arthritis Res. Ther. 12, 111 (2010).

    PubMed  PubMed Central  Google Scholar 

  84. Ginzler, E. M. et al. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res. Ther. 14, R33 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Isenberg, D. et al. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial). Ann. Rheum. Dis. 74, 2006–2015 (2015).

    CAS  PubMed  Google Scholar 

  86. Mok, C. C. Abatacept for systemic lupus erythematosus: the outlook. Expert Opin. Biol. Ther. 12, 1559–1561 (2012).

    CAS  PubMed  Google Scholar 

  87. Furie, R. et al. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 66, 379–389 (2014).

    CAS  PubMed  Google Scholar 

  88. Daikh, D. I. & Wofsy, D. Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J. Immunol. 166, 2913–2916 (2001).

    CAS  PubMed  Google Scholar 

  89. Brück, W. & Zamvil, S. S. Laquinimod, a once-daily oral drug in development for the treatment of relapsing-remitting multiple sclerosis. Expert Rev. Clin. Pharmacol. 5, 245–256 (2012).

    PubMed  Google Scholar 

  90. Jayne, D. et al. A randomized controlled study of laquinimod in active lupus nephritis patients in combination with standard of care. Ann. Rheum. Dis. 78, A164 (2013).

    Google Scholar 

  91. Michaelson, J. S., Wisniacki, N., Burkly, L. C. & Putterman, C. Role of TWEAK in lupus nephritis: a bench-to-bedside review. J. Autoimmun. 39, 130–142 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Schwartz, N. et al. Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res. Ther. 11, R143 (2009).

    PubMed  PubMed Central  Google Scholar 

  93. US National Library of Medicine. ClinicalTrials.gov[online], (2015).

  94. Lertdumrongluk, P. et al. Pharmacokinetics of mycophenolic acid in severe lupus nephritis. Kidney Int. 78, 389–395 (2010).

    CAS  PubMed  Google Scholar 

  95. Neumann, I. et al. Association between mycophenolic acid 12-h trough levels and clinical endpoints in patients with autoimmune disease on mycophenolate mofetil. Nephrol. Dial. Transplant. 23, 3514–3520 (2008).

    CAS  PubMed  Google Scholar 

  96. Djabarouti, S. et al. Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study. Arthritis Res. Ther. 12, R217 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Zahr, N. et al. Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum. 62, 2047–2054 (2010).

    CAS  PubMed  Google Scholar 

  98. Mok, C. C. Biomarkers for lupus nephritis: a critical appraisal. J. Biomed. Biotechnol. 2010, 638413 (2010).

    PubMed  PubMed Central  Google Scholar 

  99. Li, Y., Fang, X. & Li, Q. Z. Biomarkers profiling for lupus nephritis. Genom. Proteom. Bioinformat. 11, 158–165 (2013).

    CAS  Google Scholar 

  100. Watson, L. & Beresford, M. W. Urine biomarkers in juvenile-onset SLE nephritis. Pediatr. Nephrol. 28, 363–374 (2013).

    PubMed  Google Scholar 

  101. Hinze, C. H. et al. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum. 60, 2772–2781 (2009).

    PubMed  PubMed Central  Google Scholar 

  102. Watson, L. et al. Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study. Pediatr. Nephrol. 29, 397–405 (2014).

    PubMed  Google Scholar 

  103. Sui, W., Hou, X., Che, W., Yang, M. & Dai, Y. The applied basic research of systemic lupus erythematosus based on the biological omics. Genes Immun. 14, 133–146 (2013).

    CAS  PubMed  Google Scholar 

  104. Verdecchia, P. et al. Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial. Lancet 374, 525–533 (2009).

    PubMed  Google Scholar 

  105. Fullerton, B. et al. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst. Rev. 2, CD009122 (2014).

    Google Scholar 

  106. Stoffer, M. A. et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2015-207526, (2015).

  107. van Vollenhoven, R. F. et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann. Rheum. Dis. 73, 958–967 (2014).

    PubMed  Google Scholar 

  108. Mok, C. C. et al. Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis. Arthritis Rheum. 50, 2559–2568 (2004).

    PubMed  Google Scholar 

  109. Moroni, G. et al. Membranous nephropathy in systemic lupus erythematosus: long-term outcome and prognostic factors of 103 patients. Semin. Arthritis Rheum. 41, 642–651 (2012).

    PubMed  Google Scholar 

  110. Reich, H. N. et al. Persistent proteinuria and dyslipidemia increase the risk of progressive chronic kidney disease in lupus erythematosus. Kidney Int. 79, 914–920 (2011).

    CAS  PubMed  Google Scholar 

  111. Griffin, B. & Lightstone, L. Renoprotective strategies in lupus nephritis: beyond immunosuppression. Lupus 22, 1267–1273 (2013).

    CAS  PubMed  Google Scholar 

  112. Tang, C., Godfrey, T., Stawell, R. & Nikpour, M. Hydroxychloroquine in lupus: emerging evidence supporting multiple beneficial effects. Intern. Med. J. 42, 968–978 (2012).

    CAS  PubMed  Google Scholar 

  113. Olsen, N. J., Schleich, M. A. & Karp, D. R. Multifaceted effects of hydroxychloroquine in human disease. Semin. Arthritis Rheum. 43, 264–272 (2013).

    CAS  PubMed  Google Scholar 

  114. Pons-Estel, G. J. et al. Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum. 61, 830–839 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Sisó, A. et al. Previous antimalarial therapy in patients diagnosed with lupus nephritis: influence on outcomes and survival. Lupus 17, 281–288 (2008).

    PubMed  Google Scholar 

  116. Alarcón, G. S. et al. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann. Rheum. Dis. 66, 1168–1172 (2007).

    PubMed  PubMed Central  Google Scholar 

  117. Ruiz-Irastorza, G. et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 15, 577–583 (2006).

    CAS  PubMed  Google Scholar 

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  1. Department of Medicine, Tuen Mun Hospital, 23 Tsing Chung Koon Road, Hong Kong SAR, New Territories, China

    C. C. Mok

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Mok, C. Towards new avenues in the management of lupus glomerulonephritis. Nat Rev Rheumatol 12, 221–234 (2016). https://doi.org/10.1038/nrrheum.2015.174

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