Skip to main content

Advertisement

SpringerLink
Log in

The role of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Background

Plasma exchange (PLEX) in addition to standard immunosuppressive treatment in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AVV) remains controversial. The aim of this study is to evaluate the effect of PLEX on AVV outcomes.

Methods

Literature search was performed using Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov databases, and Google Scholar. The statistical meta-analysis and leave-one-out analysis were conducted using the Review Manager 5.3 and Open Meta-Analyst software, respectively.

Results

Ten studies were included in the meta-analysis comprising 1235 patients; 633 received conventional treatment and 602 were treated with PLEX in conjunction with induction therapy. PLEX was not associated with lower rates of either mortality at 3 (RR: 0.79, 95% CI: 0.19–3.25) and 12 months (RR: 0.73, 95% CI: 0.40–1.34) or ESRD at 3 (RR: 0.30, 95% CI: 0.30–2.42) and 12 months (RR: 1.32, 95% CI: 0.53–3.25). Similarly, no differences were captured concerning disease relapses (RR: 0.92, 95% CI: 0.62–1.36), the incidence of infections (RR: 1.05, 95% CI: 0.63–1.76), and severe adverse effects (RR: 1.04, 95% CI: 0.59–1.81). Time-to-event analysis revealed lower incidence of ESRD (HR: 0.71, 95% CI: 0.55–0.92) among patients who received PLEX, while the overall mortality was similar (HR: 0.96, 95% CI: 0.72–1.29) between the two groups.

Conclusion

The present meta-analysis does not support the wide use of PLEX for the management of AAV in routine clinical practice. Future well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX.

Key Points

• PLEX is not widely recommended for the management of ANCA-associated vasculitis.

• PLEX performance may reduce the overall incidence of ESRD in severe ANCA-associated vasculitis.

• Well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX on AAV-related outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jennette JC (2013) Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol 17:603–606

  2. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CGM, Mccluskey RT, Sinico RA, Rees AJ, Es LAV, Waldherr RÜD, Wiik A (1994) Nomenclature of systemic vasculitides. Arthritis Rheum 37(2):187–192

    Article  CAS  Google Scholar 

  3. Yang JJ, Jennette JC, Falk RJ (1994) Immune complex glomerulonephritis is induced in rats immunized with heterologous myeloperoxidase. Clin Exp Immunol 97(3):466–473 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8082301 [cited 2019 Nov 17]

    Article  CAS  Google Scholar 

  4. Little MA, Al-Ani B, Ren S, Al-Nuaimi H, Leite M, Alpers CE et al (2012) Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system. PLoS One 11:7(1)

    Google Scholar 

  5. Schlieben DJ, Korbet SM, Kimura RE, Schwartz MM, Lewis EJ (2005) Pulmonary-renal syndrome in a newborn with placental transmission of ANCAs. Am J Kidney Dis 45(4):758–761

    Article  Google Scholar 

  6. Walsh M (2014) Plasma exchange in antineutrophil cytoplasm antibody-associated vasculitis. Curr Opin Nephrol Hypertens 23(6):555–559

    Article  CAS  Google Scholar 

  7. Bosch X, Guilabert A, Espinosa G, Mirapeix E (2007) Treatment of antineutrophil cytoplasmic antibody associated vasculitis: a systematic review. JAMA 298(6):655–669 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17684188 [cited 2019 Nov 17]

    Article  CAS  Google Scholar 

  8. Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U, RAVE-ITN Research Group (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232

    Article  CAS  Google Scholar 

  9. Jones RB, Tervaert JWC, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR, European Vasculitis Study Group (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363(3):211–220

    Article  CAS  Google Scholar 

  10. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JWC, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C (2003) A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349(1):36–44

    Article  CAS  Google Scholar 

  11. Moiseev S, Novikov P, Jayne D, Mukhin N (2017) End-stage renal disease in ANCA-associated vasculitis. Nephrol Dial Transplant 32(2):248–253

    CAS  PubMed  Google Scholar 

  12. Little MA, Nightingale P, Verburgh CA, Hauser T, De Groot K, Savage C et al (2010) Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 69(6):1036–1043 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19574233 [cited 2019 Nov 17]

    Article  Google Scholar 

  13. Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalçındağ N, Jayne DR, Mukhtyar C (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75(9):1583–1594

    Article  CAS  Google Scholar 

  14. Walsh M, Merkel PA, Peh C-A, Szpirt WM, Puéchal X, Fujimoto S, Hawley CM, Khalidi N, Floßmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suárez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear C, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW, PEXIVAS Investigators (2020) Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 382(7):622–631

    Article  CAS  Google Scholar 

  15. Cortazar FB, Niles JL (2020) The fate of plasma exchange and glucocorticoid dosing in ANCA-associated vasculitis after PEXIVAS. Am J Kidney Dis Available from: https://linkinghub.elsevier.com/retrieve/pii/S0272638620306156 [cited 2020 May 23]

  16. Hohenstein B, Schettler V, Groot K (2020) With reasonable doubt: plasma exchange in <scp>PEXIVAS</scp>. Ther Apher Dial:1744–9987.13491 Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/1744-9987.13491 [cited 2020 May 23]

  17. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 339:b2700

    Article  Google Scholar 

  18. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 343:d5928

    Article  Google Scholar 

  19. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 355:i4919

    Article  Google Scholar 

  20. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ. 327(7414):557–560

    Article  Google Scholar 

  21. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 8:16

    Article  Google Scholar 

  22. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834

    Article  CAS  Google Scholar 

  23. Wallace BC, Schmid CH, Lau J, Trikalinos TA (2009) Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data. BMC Med Res Methodol 9(1):80

    Article  Google Scholar 

  24. Nakamura T, Matsuda T, Kawagoe Y, Ueda Y, Ebihara I, Koide H (2004) Plasmapheresis with immunosuppressive therapy vs immunosuppressive therapy alone for rapidly progressive anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis. Nephrol Dial Transplant 19(7):1935–1937

    Article  CAS  Google Scholar 

  25. Frausová D, Hrušková Z, Lánská V, Lachmanová J, Tesař V (2016) Long-term outcome of patients with ANCA-associated vasculitis treated with plasma exchange: a retrospective, single-centre study. Arthritis Res Ther 18:168

    Article  Google Scholar 

  26. Hruskova Z, Casian A, Konopasek P, Svobodova B, Frausova D, Lanska V, Tesar V, Jayne DRW (2013) Long-term outcome of severe alveolar haemorrhage in ANCA-associated vasculitis: a retrospective cohort study. Scand J Rheumatol 42(3):211–214

    Article  CAS  Google Scholar 

  27. Jayne DRW, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage COS, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RAF, Pusey CD (2007) Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 18(7):2180–2188

    Article  CAS  Google Scholar 

  28. Walsh M, Casian A, Flossmann O, Westman K, Höglund P, Pusey C, Jayne DR, European Vasculitis Study Group (EUVAS) (2013) Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int 84(2):397–402

    Article  CAS  Google Scholar 

  29. Szpirt WM, Heaf JG, Petersen J (2011) Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener’s granulomatosis—a clinical randomized controlled trial. Nephrol Dial Transplant 26(1):206–213

    Article  CAS  Google Scholar 

  30. Zäuner I, Bach D, Braun N, Krämer BK, Fünfstück R, Helmchen U, Schollmeyer P, Böhler J (2002) Predictive value of initial histology and effect of plasmapheresis on long-term prognosis of rapidly progressive glomerulonephritis. Am J Kidney Dis 39(1):28–35

    Article  Google Scholar 

  31. Frasca GM, Soverini ML, Falaschini A, Tampieri E, Vangelista A, Stefoni S (2003) Plasma exchange treatment improves prognosis of antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis: a case-control study in 26 patients from a single center. Ther Apher Dial 7(6):540–546

    Article  Google Scholar 

  32. Dhaun N, Saunders A, Bellamy CO, Gallardo RM, Manson L, Kluth DC (2015) Benefits of an expanded use of plasma exchange for anti-neutrophil cytoplasmic antibody-associated vasculitis within a dedicated clinical service clinical rheumatology and osteoporosis. BMC Musculoskelet Disord 16(1):1–10. https://doi.org/10.1186/s12891-015-0796-7

    Article  CAS  Google Scholar 

  33. Solar-Cafaggi D, Atisha-Fregoso Y, Hinojosa-Azaola A (2016) Plasmapheresis therapy in ANCA-associated vasculitides: a single-center retrospective analysis of renal outcome and mortality. J Clin Apher 31(5):411–418

    Article  Google Scholar 

  34. de Joode AA, Sanders JSF, Smid WM, Stegeman CA (2014) Plasmapheresis rescue therapy in progressive systemic ANCA-associated vasculitis: single-center results of stepwise escalation of immunosuppression. J Clin Apher 29(5):266–272

    Article  Google Scholar 

  35. Gregersen JW, Kristensen T, Krag SRP, Birn H, Ivarsen P (2012) Early plasma exchange improves outcome in PR3-ANCA-positive renal vasculitis. Clin Exp Rheumatol 30(1 Suppl 70):S39–S47

    PubMed  Google Scholar 

  36. Walsh M, Catapano F, Szpirt W, Thorlund K, Bruchfeld A, Guillevin L, Haubitz M, Merkel PA, Peh CA, Pusey C, Jayne D (2011) Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis 57(4):566–574

    Article  Google Scholar 

  37. Philip J, Sarkar RS, Pathak A (2013) Adverse events associated with apheresis procedures: Incidence and relative frequency. Asian J Transfus Sci 7(1):37–41

    Article  Google Scholar 

  38. Plasmapheresis. In: Pocket companion to Brenner and Rector’s the kidney. Elsevier; 2011 [cited 2019 Nov 20]. p. 777–88. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9781416066408000373

  39. Wing EJ, Bruns FJ, Fraley DS, Segel DP, Adler S (1980) Infectious complications with plasmapheresis in rapidly progressive glomerulonephritis. JAMA J Am Med Assoc 244(21):2423–2426

    Article  CAS  Google Scholar 

  40. Cartin-Ceba R, Diaz-Caballero L, Al-Qadi MO, Tryfon S, Fervenza FC, Ytterberg SR et al (2016) Diffuse alveolar hemorrhage secondary to antineutrophil cytoplasmic antibody-associated vasculitis: predictors of respiratory failure and clinical outcomes. Arthritis Rheumatol (Hoboken, NJ) 68(6):1467–1476 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26713723 [cited 2019 Nov 22]

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Surgery and Surgical Research NS Christeas, Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Ioannis Bellos

  2. Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Ioannis Michelakis

  3. Laboratory of Immune Regulation and Tolerance, Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    Dionysis Nikolopoulos

  4. 4th Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Dionysis Nikolopoulos

Authors
  1. Ioannis Bellos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ioannis Michelakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dionysis Nikolopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dionysis Nikolopoulos.

Ethics declarations

Disclosures

None.

Research involving human participants and/or animals

For this type of study, formal consent is not required.

Ethical approval

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

Informed consent

Informed consent was not required since no patients participated the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

Supplementary Figure 1. Risk of bias assessment in randomized controlled trials (PNG 514 kb)

High resolution image (TIF 4268 kb)

ESM 2

(DOCX 282 kb)

ESM 3

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bellos, I., Michelakis, I. & Nikolopoulos, D. The role of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis. Clin Rheumatol 40, 1447–1456 (2021). https://doi.org/10.1007/s10067-020-05390-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05390-z

Keywords

Search

Navigation