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2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis
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  1. Antonis Fanouriakis1,2,
  2. Myrto Kostopoulou3,
  3. Kim Cheema4,
  4. Hans-Joachim Anders5,
  5. Martin Aringer6,
  6. Ingeborg Bajema7,
  7. John Boletis8,
  8. Eleni Frangou9,
  9. Frederic A Houssiau10,
  10. Jane Hollis11,
  11. Adexandre Karras12,
  12. Francesca Marchiori13,
  13. Stephen D Marks14,
  14. Gabriella Moroni15,
  15. Marta Mosca16,
  16. Ioannis Parodis17,
  17. Manuel Praga18,
  18. Matthias Schneider19,
  19. Josef S Smolen20,
  20. Vladimir Tesar21,
  21. Maria Trachana22,
  22. Ronald F van Vollenhoven23,
  23. Alexandre E Voskuyl24,
  24. Y K Onno Teng25,
  25. Bernadette van Leew26,
  26. George Bertsias27,
  27. David Jayne4,
  28. Dimitrios T Boumpas1,28
  1. 1 Rheumatology and Clinical Immunology Unit, "Attikon" University Hospital, Athens, Greece
  2. 2 Department of Rheumatology, "Asklepieion" General Hospital, Athens, Greece
  3. 3 Department of Nephrology, "G. Gennimatas" General Hospital, Athens, Greece
  4. 4 Department of Medicine, Cambridge University, Cambridge, UK
  5. 5 Division of Nephrology, Department of Medicine IV, University Hospital LMU Munich, Munich, Germany
  6. 6 Division of Rheumatology, Department of Medicine III, University Medical Center & Faculty of Medicine Carl Gustav Carus at the TU Dresden, Dresden, Germany
  7. 7 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
  8. 8 Nephrology Department and Renal Transplantation Unit, "Laikon" Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece
  9. 9 Department of Nephrology, Limassol General Hospital, Limassol, Cyprus
  10. 10 Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
  11. 11 Lupus nurse specialist, Addenbrooke's Hospital, Cambridge, UK
  12. 12 Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France
  13. 13 Lupus Europe, Rome, Italy
  14. 14 University College London Great Ormond Street Institute of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK
  15. 15 Nephrology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  16. 16 Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  17. 17 Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  18. 18 Nephrology Department, Research Institute Hospital Universitario 12 de Octubre (i+12), Department of Medicine, Complutense University of Madrid, Madrid, Spain
  19. 19 Department of Rheumatology & Hiller Research Unit Rheumatology, UKD, Heinrich-Heine University, Duesseldorf, Germany
  20. 20 Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  21. 21 Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
  22. 22 Pediatric Immunology and Rheumatology Referral Center, First Pediatric Clinic, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
  23. 23 Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
  24. 24 Rheumatology and Immunology Center, Amsterdam University Medical Center, Amsterdam, The Netherlands
  25. 25 Centre of expertise for Lupus-, Vasculitis- and Complement-mediated Systemic autoimmune diseases, Department of Internal Medicine – section Nephrology, Leiden University Medical Center, Leiden, The Netherlands
  26. 26 Lupus Europe, Essex, UK
  27. 27 Rheumatology, Clinical Immunology and Allergy, University Hospital of Heraklion, Heraklion, Greece
  28. 28 Laboratory of Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
  1. Correspondence to Dr Dimitrios T Boumpas, Rheumatology and Clinical Immunology Unit, "Attikon" University Hospital, Athens 124 62, Greece; boumpasd{at}uoc.gr

Abstract

Objective To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus nephritis (LN).

Methods Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements.

Results The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5–0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2–3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3–0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease.

Conclusions We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

  • systemic lupus erythematosus
  • treatment
  • lupus nephritis
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Footnotes

  • Handling editor David S Pisetsky

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  • GB, DJ and DTB contributed equally.

  • Contributors AF, MK and KC performed the systematic literature review and AF drafted the manuscript. GB supervised the methodology and edited the manuscript. DJ and DTB convened and supervised the project and edited the manuscript. All authors edited the manuscript and accepted its final form.

  • Funding This study was funded by European League against Rheumatism.

  • Competing interests AF reports personal fees from GSK, Abbvie, Amgen, Enorasis, Roche and Genesis Pharma, outside the submitted work. HJA reports personal fees from GSK, Astra Zeneca and Janssen, during the conduct of the study; personal fees from Secarna, Inositec, Previpharma and Noxxon, outside the submitted work. MA reports honoraria fees from GSK and Roche, outside the submitted work; FH reports honoraria fees from GSL, outside the submitted work. MP reports personal fees from Otsuka, grants and personal fees from Alexion, personal fees from Retrophin, outside the submitted work. YKOT reports grants from GSK, personal fees from Aurinia Pharmaceuticals, personal fees from Novartis, during the conduct of the study. MT reports grants from Abbvie, BMS, Novartis, Pfize and Roche and honoraria fees from Novartis, outside the submitted work. DJ reports personal fees from Astra-Zeneca, Aurinia, Boehringer-Ingelheim, grants and personal fees from Chemocentryx, GSK, Roche/Genentech, and Sanofi-Genzyme, personal fees and other from Vifor, outside the submitted work.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Detailed data relating to this article will be published separately and are also available upon request.

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