Download PDF
Nephrologie aktuell 2024; 28(06): 248-256
DOI: 10.1055/a-2275-4681
Schwerpunkt
Nephrologie

Die Herausforderung der Lupusnephritis

Aktuelle Erkenntnisse und Behandlungsansätze
Jonas Zimmermann
1   Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité – Universitätsmedizin Berlin, Berlin
2   Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin und Max-Delbrück-Centrum; Center für molekulare Medizin in der Helmholtz-Gemeinschaft Deutscher Forschungszentren, Berlin
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

ZUSAMMENFASSUNG

Die Lupusnephritis (LN) ist eine schwerwiegende Manifestation des systemischen Lupus erythematodes (SLE) und betrifft 20–60 % der SLE-Patienten. Ihre Pathophysiologie ist komplex; sie umfasst das humorale Immunsystem, zelluläre Immunmechanismen, das Komplementsystem sowie genetische Faktoren. Ein regelmäßiges Screening von SLE-Patienten auf LN ist entscheidend und sollte serologische Untersuchungen sowie eine Urinanalyse beinhalten. Bei Verdacht auf LN ist eine Nierenbiopsie indiziert, wobei das Fullhouse-Ablagerungsmuster (IgG, IgA, IgM, C1q, C3) ein charakteristisches Merkmal ist. Die Therapie der LN entwickelt sich stetig weiter und neue Therapieansätze werden erforscht. Zur Induktionstherapie gehören Glukokortikoide, Hydroxychloroquin und mindestens ein weiteres Immunsuppressivum. Nach dem Erreichen eines Therapieansprechens folgt eine Erhaltungstherapie, für die Mycophenolatmofetil (MMF) oder Mycophenolsäure (MPA) als erste Wahl gelten.



Publication History

Article published online:
24 July 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Rovin BH, Ayoub IM, Chan TM. et al KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. Kidney Int 2024; 105: S1-S69
    CrossrefPubMedSearch in Google Scholar
  • 2 Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc Nephrol 2017; 12: 825-835
    CrossrefPubMedSearch in Google Scholar
  • 3 Parikh SV, Almaani S, Brodsky S. et al Update on lupus nephritis: core curriculum 2020. Am J Kidney Dis 2020; 76: 265-281
    CrossrefPubMedSearch in Google Scholar
  • 4 Rodríguez-Almaraz E, Gutiérrez-Solís E, Rabadán E. et al Something new about prognostic factors for lupus nephritis? A systematic review. Lupus 2021; 30: 2256-2267
    CrossrefPubMedSearch in Google Scholar
  • 5 Parodis I, Tamirou F, Houssiau FA. Prediction of prognosis and renal outcome in lupus nephritis. Lupus Sci Med 2020; 07: e000389
    CrossrefPubMedSearch in Google Scholar
  • 6 Tektonidou MG, Dasgupta A, Ward MM. Risk of end-stage renal disease in patients with lupus nephritis, 1971–2015: A systematic review and Bayesian meta-analysis. Arthritis Rheumatol 2016; 68: 1432-1441
    CrossrefPubMedSearch in Google Scholar
  • 7 Izmirly PM, Wan I, Sahl S. et al The incidence and prevalence of systemic lupus erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program. Arthritis Rheumatol 2017; 69: 2006-2017
    CrossrefPubMedSearch in Google Scholar
  • 8 Ortega LM, Schultz DR, Lenz O. et al Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions. Lupus 2010; 19: 557-574
    CrossrefPubMedSearch in Google Scholar
  • 9 Somers EC, Marder W, Cagnoli P. et al Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. Arthritis Rheumatol 2014; 66: 369-378
    CrossrefPubMedSearch in Google Scholar
  • 10 Alarcón GS, McGwin Jr. G, Petri M. et al Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 2002; 11: 95-101
    CrossrefPubMedSearch in Google Scholar
  • 11 Feldman CH, Hiraki LT, Liu J. et al Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 2000–2004. Arthritis Rheum 2013; 65: 753-763
    CrossrefPubMedSearch in Google Scholar
  • 12 Contreras G, Lenz O, Pardo V. et al Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int 2006; 69: 1846-1851
    CrossrefPubMedSearch in Google Scholar
  • 13 Rovin BH, Caster DJ, Cattran DC. et al Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019; 95: 281-295
    CrossrefPubMedSearch in Google Scholar
  • 14 Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol 2013; 24: 1357-1366
    CrossrefPubMedSearch in Google Scholar
  • 15 Pang Y, Yang XW, Song Y. et al Anti-C1q autoantibodies from active lupus nephritis patients could inhibit the clearance of apoptotic cells and complement classical pathway activation mediated by C1q in vitro. Immunobiology 2014; 219: 980-989
    CrossrefPubMedSearch in Google Scholar
  • 16 Birmingham DJ, Bitter JE, Ndukwe EG. et al Relationship of circulating anti-C3b and anti-C1q IgG to lupus nephritis and its flare. Clin J Am Soc Nephrol 2016; 11: 47-53
    CrossrefPubMedSearch in Google Scholar
  • 17 Villanueva E, Yalavarthi S, Berthier CC. et al Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus. J Immunol 2011; 187: 538-552
    CrossrefPubMedSearch in Google Scholar
  • 18 Hakkim A, Fürnrohr BG, Amann K. et al Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A 2010; 107: 9813-9818
    CrossrefPubMedSearch in Google Scholar
  • 19 Chung SA, Brown EE, Williams AH. et al Lupus nephritis susceptibility loci in women with systemic lupus erythematosus. J Am Soc Nephrol 2014; 25: 2859-2870
    CrossrefPubMedSearch in Google Scholar
  • 20 Niu Z, Zhang P, Tong Y. Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis. Int J Rheum Dis 2015; 18: 17-28
    CrossrefPubMedSearch in Google Scholar
  • 21 Moroni G, Vercelloni PG, Quaglini S. et al Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis. Ann Rheum Dis 2018; 77: 1318-1325
    CrossrefPubMedSearch in Google Scholar
  • 22 Fanouriakis A, Kostopoulou M, Cheema K. et al 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. Ann Rheum Dis 2020; 79: 713-723
    CrossrefPubMedSearch in Google Scholar
  • 23 Bajema IM, Wilhelmus S, Alpers CE. et al Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int 2018; 93: 789-796
    CrossrefPubMedSearch in Google Scholar
  • 24 Weening JJ, D’Agati VD, Schwartz MM. et al The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15: 241-250
    CrossrefPubMedSearch in Google Scholar
  • 25 Kudose S, Santoriello D, Bomback AS. et al Sensitivity and specificity of pathologic findings to diagnose lupus nephritis. Clin J Am Soc Nephrol 2019; 14: 1605-1615
    CrossrefPubMedSearch in Google Scholar
  • 26 Tamirou F, D’Cruz D, Sangle S. 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 2016; 75: 526-531
    CrossrefPubMedSearch in Google Scholar
  • 27 Antonis F, Myrto K, Jeanette A. et al EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 2024; 83: 15
    CrossrefPubMedSearch in Google Scholar
  • 28 Touma Z, Urowitz MB, Ibañez D. et al Time to recovery from proteinuria in patients with lupus nephritis receiving standard treatment. J Rheumatol 2014; 41: 688-697
    CrossrefPubMedSearch in Google Scholar
  • 29 Bock M, Heijnen I, Trendelenburg M. Anti-C1q antibodies as a follow-up marker in SLE patients. PLoS One 2015; 10: e0123572
    CrossrefPubMedSearch in Google Scholar
  • 30 The EMPA-KIDNEY Collaborative Group. Herrington WG, Staplin N. et al Empagliflozin in patients with chronic kidney disease. N Engl J Med 2022; 388: 117-127
    CrossrefPubMedSearch in Google Scholar
  • 31 Heerspink HJL, Stefánsson BV, Correa-Rotter R. et al Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020; 383: 1436-1446
    CrossrefPubMedSearch in Google Scholar
  • 32 Oliva-Damaso N, Payan J, Oliva-Damaso E. et al Lupus podocytopathy: an Overview. Adv Chronic Kidney Dis 2019; 26: 369-375
    CrossrefPubMedSearch in Google Scholar
  • 33 Mok CC, Teng YKO, Saxena R. et al Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol 2023; 19: 227-238
    CrossrefPubMedSearch in Google Scholar
  • 34 Li X, Ren H, Zhang Q. et al Mycophenolate mofetil or tacrolimus compared with intravenous cyclophosphamide in the induction treatment for active lupus nephritis. Nephrol Dial Transplant 2012; 27: 1467-1472
    CrossrefPubMedSearch in Google Scholar
  • 35 Rathi M, Goyal A, Jaryal A. et al Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int 2016; 89: 235-242
    CrossrefPubMedSearch in Google Scholar
  • 36 Houssiau FA, Vasconcelos C, D’Cruz D. 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 2002; 46: 2121-2131
    CrossrefPubMedSearch in Google Scholar
  • 37 Houssiau FA, Vasconcelos C, D’Cruz D. 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 2010; 69: 61-64
    CrossrefPubMedSearch in Google Scholar
  • 38 Liu Z, Zhang H, Liu Z. et al Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med 2015; 162: 18-26
    CrossrefPubMedSearch in Google Scholar
  • 39 Chen W, Tang X, Liu Q. 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 2011; 57: 235-244
    CrossrefPubMedSearch in Google Scholar
  • 40 Rovin BH, Adler SG, Barratt J. et al Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100: 753-779
    CrossrefPubMedSearch in Google Scholar
  • 41 Rovin BH, Teng YKO, Ginzler EM. et al Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2021; 397: 2070-2080
    CrossrefPubMedSearch in Google Scholar
  • 42 Furie R, Rovin BH, Houssiau F. et al Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 2020; 383: 1117-1128
    CrossrefPubMedSearch in Google Scholar
  • 43 Rovin BH, Furie R, Teng YKO. et al A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis. Kidney Int 2022; 101: 403-413
    CrossrefPubMedSearch in Google Scholar
  • 44 Dooley MA, Jayne D, Ginzler EM. et al Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 2011; 365: 1886-1895
    CrossrefPubMedSearch in Google Scholar
  • 45 Houssiau FA, D’Cruz D, Sangle S. et al Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 2010; 69: 2083-2089
    CrossrefPubMedSearch in Google Scholar
  • 46 Saxena A, Ginzler EM, Gibson K. et al Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 AURORA 2 clinical trial. Arthritis Rheumatol. 2023; DOI. 10.1002/art.42657. doi:10.1002/art.42657.
  • 47 Mok CC, Hamijoyo L, Kasitanon N. et al The Asia-Pacific League of Associations for Rheumatology consensus statements on the management of systemic lupus erythematosus. Lancet Rheumatol 2021; 03: e517-e531
    CrossrefPubMedSearch in Google Scholar
  • 48 Rovin BH, Furie R, Latinis K. et al Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum 2012; 64: 1215-1226
    CrossrefPubMedSearch in Google Scholar
  • 49 Weidenbusch M, Römmele C, Schröttle A. et al Beyond the LUNAR trial. Efficacy of rituximab in refractory lupus nephritis. Nephrol Dial Transplant 2013; 28: 106-111
    CrossrefPubMedSearch in Google Scholar
  • 50 Furie RA, Aroca G, Cascino MD. et al B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2022; 81: 100-107
    CrossrefPubMedSearch in Google Scholar
  • 51 Jayne D, Rovin B, Mysler EF. et al Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis 2022; 81: 496-506
    CrossrefPubMedSearch in Google Scholar
  • 52 Mok CC. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat Rev Nephrol 2009; 05: 212-220
    CrossrefPubMedSearch in Google Scholar
  • 53 Mok CC, Ying KY, Yim CW. et al Very long-term outcome of pure lupus membranous nephropathy treated with glucocorticoid and azathioprine. Lupus 2009; 18: 1091-1095
    CrossrefPubMedSearch in Google Scholar
  • 54 Austin 3 rd HA, Illei GG, Braun MJ. et al Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20: 901-911
    CrossrefPubMedSearch in Google Scholar
  • 55 Radhakrishnan J, Moutzouris DA, Ginzler EM. et al Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 2010; 77: 152-160
    CrossrefPubMedSearch in Google Scholar
  • 56 Morris HK, Canetta PA, Appel GB. Impact of the ALMS and MAINTAIN trials on the management of lupus nephritis. Nephrol Dial Transplant 2013; 28: 1371-1376
    CrossrefPubMedSearch in Google Scholar
  • 57 Ioannidis JP, Boki KA, Katsorida ME. et al Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. Kidney Int 2000; 57: 258-264
    CrossrefPubMedSearch in Google Scholar
  • 58 Moroni G, Gallelli B, Quaglini S. et al Withdrawal of therapy in patients with proliferative lupus nephritis: long-term follow-up. Nephrol Dial Transplant 2006; 21: 1541-1548
    CrossrefPubMedSearch in Google Scholar
  • 59 Parikh SV, Alvarado A, Malvar A. et al The Kidney Biopsy in Lupus Nephritis: Past, Present, and Future. Semin Nephrol 2015; 35: 465-477
    CrossrefPubMedSearch in Google Scholar
  • 60 Narváez J, Ricse M, Gomà M. et al The value of repeat biopsy in lupus nephritis flares. Medicine (Baltimore) 2017; 96: e7099
    CrossrefPubMedSearch in Google Scholar
  • 61 Li C, Yap DYH, Chan G. et al Clinical outcomes and clinico-pathological correlations in lupus nephritis with kidney biopsy showing thrombotic microangiopathy. J Rheumatol 2019; 46: 1478-1484
    CrossrefPubMedSearch in Google Scholar
  • 62 Pattanashetti N, Anakutti H, Ramachandran R. et al Effect of thrombotic microangiopathy on clinical outcomes in Indian patients with lupus nephritis. Kidney Int Rep 2017; 02: 844-849
    CrossrefPubMedSearch in Google Scholar