Die Herausforderung der Lupusnephritis

Jonas Zimmermann

doi:10.1055/a-2275-4681

Nephrologie aktuell, Table of Contents

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

¹Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité – Universitätsmedizin Berlin, Berlin

²Experimental and Clinical Research Center, Charité – Universitätsmedizin Berlin und Max-Delbrück-Centrum; Center für molekulare Medizin in der Helmholtz-Gemeinschaft Deutscher Forschungszentren, Berlin

› Author Affiliations

Abstract

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.

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References

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
2 Almaani S, Meara A, Rovin BH. Update on lupus nephritis. Clin J Am Soc Nephrol 2017; 12: 825-835
3 Parikh SV, Almaani S, Brodsky S. et al Update on lupus nephritis: core curriculum 2020. Am J Kidney Dis 2020; 76: 265-281
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
5 Parodis I, Tamirou F, Houssiau FA. Prediction of prognosis and renal outcome in lupus nephritis. Lupus Sci Med 2020; 07: e000389
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
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
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
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
10 Alarcón GS, McGwin Jr. G, Petri M. et al Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 2002; 11: 95-101
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
12 Contreras G, Lenz O, Pardo V. et al Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int 2006; 69: 1846-1851
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
14 Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol 2013; 24: 1357-1366
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
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
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
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
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
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
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
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
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
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
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
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
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
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
29 Bock M, Heijnen I, Trendelenburg M. Anti-C1q antibodies as a follow-up marker in SLE patients. PLoS One 2015; 10: e0123572
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
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
32 Oliva-Damaso N, Payan J, Oliva-Damaso E. et al Lupus podocytopathy: an Overview. Adv Chronic Kidney Dis 2019; 26: 369-375
33 Mok CC, Teng YKO, Saxena R. et al Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol 2023; 19: 227-238
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
52 Mok CC. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat Rev Nephrol 2009; 05: 212-220
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
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
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
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
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
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
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
60 Narváez J, Ricse M, Gomà M. et al The value of repeat biopsy in lupus nephritis flares. Medicine (Baltimore) 2017; 96: e7099
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
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