Skip to main content
SpringerLink
Log in

Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence

Rheumatology International volume 37, pages 1249–1255 (2017)Cite this article

Abstract

In this study, we aimed to systematically review available literature on the efficacy of eculizumab for the treatment of renal involvement in patients with systemic lupus erythematosus (SLE). We conducted a literature search developed a priori, to identify articles reporting clinical experience with the use of eculizumab in SLE patients, focusing on renal involvement. The search strategy was applied to Ovid MEDLINE, EMBASE, In-Process and Other Non-Indexed Citation, Cochrane Central Register of Controlled Trials and Scopus from 2006 to present. Abstracts from EULAR and ACR congresses were also screened. We included six publications describing the renal outcome in SLE patients receiving eculizumab. Five out of six cases described the occurrence of thrombotic microangiopathy (TMA) in renal biopsies of patients with known SLE; three cases with biopsy-proven lupus nephritis (LN) and two patients with SLE-related antiphospholipid syndrome without histologic evidence of LN. One study reported the outcome of a patient with severe refractory LN successfully treated with eculizumab. All patients, regardless of the presence of concomitant LN, presented with severe hypocomplementemia and renal function impairment. All patients showed a sustained improvement of renal function and normalization of complement parameters after treatment with eculizumab[median follow-up 9 months (1–17)]. Despite the limitations of the currently available evidence, existing data are promising and provide preliminary support for the use of eculizumab in selected cases of SLE with renal involvement, especially in the presence of TMA, or in patients with refractory LN.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Wu H, Zhao M, Tan L, Lu Q (2016) The key culprit in the pathogenesis of systemic lupus erythematosus: aberrant DNA methylation. Autoimmun Rev 15:684–689. doi:10.1016/j.autrev.2016.03.002

    Article  CAS  PubMed  Google Scholar 

  2. Lipsky PE (2001) Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2:764–766. doi:10.1038/ni0901-764

    Article  CAS  PubMed  Google Scholar 

  3. Mak A, Kow NY (2014) The pathology of T cells in systemic lupus erythematosus. J Immunol Res 2014:419029. doi:10.1155/2014/419029

    Article  PubMed  PubMed Central  Google Scholar 

  4. Schneider M (2016) Pitfalls in lupus. Autoimmun Rev. doi:10.1016/j.autrev.2016.07.033

    PubMed  Google Scholar 

  5. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA et al (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349:1526–1533. doi:10.1056/NEJMoa021933

    Article  CAS  PubMed  Google Scholar 

  6. Pisetsky DS (2015) Anti-DNA antibodies—quintessential biomarkers of SLE. Nat Rev Rheumatol 12:102–110. doi:10.1038/nrrheum.2015.151

    Article  PubMed  Google Scholar 

  7. Frieri M, Stampfl H (2016) Systemic lupus erythematosus and atherosclerosis: review of the literature. Autoimmun Rev 15:16–21. doi:10.1016/j.autrev.2015.08.007

    Article  CAS  PubMed  Google Scholar 

  8. Elkon KB, Santer DM (2012) Complement, interferon and lupus. Curr Opin Immunol 24:665–670. doi:10.1016/j.coi.2012.08.004

    Article  CAS  PubMed  Google Scholar 

  9. Carroll MC (2000) A protective role for innate immunity in autoimmune disease. Clin Immunol 95:S30–S38. doi:10.1006/clim.1999.4813

    Article  CAS  PubMed  Google Scholar 

  10. Kaya Z, Afanasyeva M, Wang Y, Dohmen KM, Schlichting J, Tretter T et al (2001) Contribution of the innate immune system to autoimmune myocarditis: a role for complement. Nat Immunol 2:739–745. doi:10.1038/90686

    Article  CAS  PubMed  Google Scholar 

  11. Fleming SD, Shea-Donohue T, Guthridge JM, Kulik L, Waldschmidt TJ, Gipson MG et al (2002) Mice deficient in complement receptors 1 and 2 lack a tissue injury-inducing subset of the natural antibody repertoire. J Immunol 169:2126–2133

    Article  CAS  PubMed  Google Scholar 

  12. Carroll MC (2000) The role of complement in B cell activation and tolerance. Adv Immunol 74:61–88

    Article  CAS  PubMed  Google Scholar 

  13. Barilla-LaBarca ML, Toder K, Furie R (2013) Targeting the complement system in systemic lupus erythematosus and other diseases. Clin Immunol 148:313–321. doi:10.1016/j.clim.2013.02.014

    Article  CAS  PubMed  Google Scholar 

  14. Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA (1996) Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5. Proc Natl Acad Sci USA 93:8563–8568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Belot A, Cimaz R (2012) Monogenic forms of systemic lupus erythematosus: new insights into SLE pathogenesis. Pediatr Rheumatol Online J 10:21. doi:10.1186/1546-0096-10-21

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lee YH, Witte T, Momot T, Schmidt RE, Kaufman KM, Harley JB et al (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52:3966–3974. doi:10.1002/art.21484

    Article  CAS  PubMed  Google Scholar 

  17. Jönsen A, Nilsson SC, Ahlqvist E, Svenungsson E, Gunnarsson I, Eriksson KG et al (2011) Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus. Arthritis Res Ther 13:R206. doi:10.1186/ar3539

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hillmen P, Hall C, Marsh JCW, Elebute M, Bombara MP, Petro BE et al (2004) Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 350:552–559. doi:10.1056/NEJMoa031688

    Article  CAS  PubMed  Google Scholar 

  19. Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C et al (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181. doi:10.1056/NEJMoa1208981

    Article  CAS  PubMed  Google Scholar 

  20. Oku K, Nakamura H, Kono M, Ohmura K, Kato M, Bohgaki T et al (2016) Complement and thrombosis in the antiphospholipid syndrome. Autoimmun Rev. doi:10.1016/j.autrev.2016.07.020

    Google Scholar 

  21. Huda R, Tüzün E, Christadoss P (2014) Targeting complement system to treat myasthenia gravis. Rev Neurosci 25:575–583. doi:10.1515/revneuro-2014-0021

    Article  CAS  PubMed  Google Scholar 

  22. Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, Ricklin D, Lambris JD (2015) Applying complement therapeutics to rare diseases. Clin Immunol 161:225–240. doi:10.1016/j.clim.2015.08.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kessler RA, Mealy MA, Levy M (2016) Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol 18:2. doi:10.1007/s11940-015-0387-9

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shapiro R, Chin-Yee I, Lam S (2015) Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity. Clin Case Reports 3:942–944. doi:10.1002/ccr3.399

    Article  Google Scholar 

  25. Manrique J, Cravedi P (2014) Role of monoclonal antibodies in the treatment of immune-mediated glomerular diseases. Nefrol Publicación Of La Soc Española Nefrol 34:388–397. doi:10.3265/Nefrologia.pre2014.Feb.12506

    Google Scholar 

  26. Lonze BE, Singer AL, Montgomery RA (2010) Eculizumab and renal transplantation in a patient with CAPS. N Engl J Med 362:1744–1745. doi:10.1056/NEJMc0910965

    Article  CAS  PubMed  Google Scholar 

  27. Vivarelli M, Pasini A, Emma F (2012) Eculizumab for the treatment of dense-deposit disease. N Engl J Med 366:1163–1165. doi:10.1056/NEJMc1111953

    Article  CAS  PubMed  Google Scholar 

  28. Kulkarni S, Kirkiles-Smith NC, Deng YH, Formica RN, Moeckel G, Broecker V et al (2016) Eculizumab therapy for chronic antibody-mediated injury in kidney transplant recipients: a pilot, randomized-controlled trial. Am J Transplant. doi:10.1111/ajt.14001

    Google Scholar 

  29. Coppo R, Peruzzi L, Amore A, Martino S, Vergano L, Lastauka I et al (2015) Dramatic effects of eculizumab in a child with diffuse proliferative lupus nephritis resistant to conventional therapy. Pediatr Nephrol 30:167–172. doi:10.1007/s00467-014-2944-y

    Article  PubMed  Google Scholar 

  30. El-Husseini A, Hannan S, Awad A, Jennings S, Cornea V, Sawaya BP (2014) Thrombotic microangiopathy in systemic lupus erythematosus: efficacy of eculizumab. Am J Kidney Dis 65:127–130. doi:10.1053/j.ajkd.2014.07.031

    Article  PubMed  Google Scholar 

  31. Boneparth A, Moorthy LN, Weiss L, Rajasekhar H, Murphy S, Drachtman RA (2015) Complement inhibition in the treatment of SLE-associated thrombotic thrombocytopenic purpura. Glob Pediatr Heal 2:2015–2017. doi:10.1177/2333794X15570150

    Google Scholar 

  32. Hadaya K, Ferrari-Lacraz S, Fumeaux D, Boehlen F, Toso C, Moll S et al (2011) Eculizumab in acute recurrence of thrombotic microangiopathy after renal transplantation. Am J Transplant 11:2523–2527. doi:10.1111/j.1600-6143.2011.03696.x

    Article  CAS  PubMed  Google Scholar 

  33. Kronbichler A, Frank R, Kirschfink M, Szilágyi Á, Csuka D, Prohászka Z et al (2014) Efficacy of eculizumab in a patient with immunoadsorption-dependent catastrophic antiphospholipid syndrome: a case report. Medicine (Baltimore) 93:e143. doi:10.1097/MD.0000000000000143

    Article  CAS  Google Scholar 

  34. Pickering MC, Ismajli M, Condon MB, McKenna N, Hall AE, Lightstone L et al (2015) Eculizumab as rescue therapy in severe resistant lupus nephritis. Rheumatol (United Kingdom) 54:2286–2288. doi:10.1093/rheumatology/kev307

    Google Scholar 

  35. Tektonidou MG, Sotsiou F, Moutsopoulos HM (2008) Antiphospholipid syndrome (APS) nephropathy in catastrophic, primary, and systemic lupus erythematosus-related APS. J Rheumatol 35:1983–1988

    CAS  PubMed  Google Scholar 

  36. Tektonidou MG, Sotsiou F, Nakopoulou L, Vlachoyiannopoulos PG, Moutsopoulos HM (2004) Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations, and long-term outcome. Arthritis Rheum 50:2569–2579. doi:10.1002/art.20433

    Article  PubMed  Google Scholar 

  37. Canaud G, Kamar N, Anglicheau D, Esposito L, Rabant M, Noël L-H et al (2013) Eculizumab improves posttransplant thrombotic microangiopathy due to antiphospholipid syndrome recurrence but fails to prevent chronic vascular changes. Am J Transplant 13:2179–2185. doi:10.1111/ajt.12319

    Article  CAS  PubMed  Google Scholar 

  38. Sciascia S, Cuadrado MJ, Khamashta M, Roccatello D (2014) Renal involvement in antiphospholipid syndrome. Nat Rev Nephrol 10:279–289. doi:10.1038/nrneph.2014.38

    Article  CAS  PubMed  Google Scholar 

  39. Miyasaka N, Miura O, Kawaguchi T, Arima N, Morishita E, Usuki K et al (2016) Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review. Int J Hematol 103:703–712. doi:10.1007/s12185-016-1946-x

    Article  CAS  PubMed  Google Scholar 

  40. De Sousa Amorim E, Blasco M, Quintana L, Sole M, de Cordoba SR, Campistol JM (2015) Eculizumab in pregnancy-associated atypical hemolytic uremic syndrome: insights for optimizing management. J Nephrol 28:641–645. doi:10.1007/s40620-015-0173-5

    Article  Google Scholar 

  41. Sciascia S, Baldovino S, Schreiber K, Solfietti L, Roccatello D (2015) Antiphospholipid Syndrome and the Kidney. Semin Nephrol 35:478–486. doi:10.1016/j.semnephrol.2015.08.009

    Article  CAS  PubMed  Google Scholar 

  42. Moroni G, Doria A, Giglio E et al (2016) Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study. J Autoimmun 74:194–200. doi:10.1016/j.jaut.2016.06.012

    Article  PubMed  Google Scholar 

  43. Furie R, Matis L, Rollins S et al (2004) A single dose, placebocontrolled, double blind, phase I study of the humanized anti-C5 antibody h5G1.1 in patients with systemic lupus erythematosus. Arthritis Rheum 50:S35–S747

    Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Hospital, University of Turin, piazza del donatore di Sangue 3, 10054, Turin, Italy

      Savino Sciascia, Massimo Radin, Irene Cecchi & Dario Roccatello

    2. Department of Clinical and Biological Sciences, SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital, University of Turin, Turin, Italy

      Savino Sciascia & Dario Roccatello

    3. Division of Rheumatology, Russell/Engleman Research Center, University of California, San Francisco, San Francisco, CA, USA

      Jinoos Yazdany & Maria Dall’Era

    4. First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

      Maria Tektonidou

    Authors
    1. Savino Sciascia
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Massimo Radin
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Jinoos Yazdany
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Maria Tektonidou
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Irene Cecchi
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Dario Roccatello
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Maria Dall’Era
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Savino Sciascia.

    Ethics declarations

    Ethical approval

    This article does not contain any studies with human participants or animals performed by any of the authors.

    Conflict of interest

    The authors declare no conflict of interest and declare no support from any organisation for the submitted work; no financial relationships with any organisations might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

    Additional information

    S. Sciascia and M. Radin equally contributed to this manuscript.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOC 63 KB)

    Rights and permissions

    Reprints and Permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Sciascia, S., Radin, M., Yazdany, J. et al. Expanding the therapeutic options for renal involvement in lupus: eculizumab, available evidence. Rheumatol Int 37, 1249–1255 (2017). https://doi.org/10.1007/s00296-017-3686-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00296-017-3686-5

    Keywords

    search

    Navigation