Lupus Nephritis
By:
Juan M. Mejia-Vilet Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

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  • 1.

    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 68: 14321441, 2016 10.1002/art.39594 PubMed

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  • 2.

    Rovin BH, Ayoub IM, Chan TM, Liu ZH, Mejía-Vilet JM, Floege J: KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. Kidney Int 105: S1S69, 2024 10.1016/j.kint.2023.09.002 PubMed

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  • 3.

    Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae S-C, et al.: EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 83: 1529, 2024 10.1136/ard-2023-224762 PubMed

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  • 4.

    Rojas-Rivera JE, García-Carro C, Ávila AI, Espino M, Espinosa M, Fernández-Juárez G, et al.: Consensus document of the Spanish Group for the Study of the Glomerular Diseases (GLOSEN) for the diagnosis and treatment of lupus nephritis. Nefrologia (Engl Ed) 43: 647, 2023 10.1016/j.nefroe.2023.05.006 PubMed

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  • 5.

    Arnaud L, Tektonidou MG: Long-term outcomes in systemic lupus erythematosus: Trends over time and major contributors. Rheumatology (Oxford) 59: v29v38, 2020 10.1093/rheumatology/keaa382 PubMed

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  • 6.

    Reid S, Alexsson A, Frodlund M, Morris D, Sandling JK, Bolin K, et al.: High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Ann Rheum Dis 79: 363369, 2020 10.1136/annrheumdis-2019-216227 PubMed

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  • 7.

    Lichtnekert J, Anders HJ: Lupus nephritis-related chronic kidney disease. Nat Rev Rheumatol 20: 699711, 2024 10.1038/s41584-024-01158-w PubMed

  • 8.

    Fava A, Wagner CA, Guthridge CJ, Kheir J, Macwna S, DeJager W, et al.; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network: Association of autoantibody concentrations and trajectories with lupus nephritis histologic features and treatment response. Arthritis Rheumatol 76: 16111622, 2024 10.1002/ART.42941 PubMed

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  • 9.

    Carlucci PM, Li J, Fava A, Deonaraine KK, Wofsy D, James JA, et al.; Accelerating Medicines Partnership (AMP) RA/SLE Network: High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership. Rheumatology (Oxford) 61: 43354343, 2022 10.1093/rheumatology/keac067 PubMed

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  • 10.

    Ravindran A, Casal Moura M, Fervenza FC, Nasr SH, Alexander MP, Fidler ME, et al.: In patients with membranous lupus nephritis, exostosin-positivity and exostosin-negativity represent two different phenotypes. J Am Soc Nephrol 32: 695706, 2021 10.1681/ASN.2020081181 PubMed

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  • 11.

    Miller PP, Caza T, Larsen CP, Charu V: EXT1 and NCAM1-associated membranous lupus nephritis in a cohort of patients undergoing repeat kidney biopsies. Nephrol Dial Transplant 38: 396404, 2023 10.1093/ndt/gfac058 PubMed

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  • 12.

    Arazi A Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, et al.; Accelerating Medicines Partnership in SLE network: The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol 20: 902914, 2019 10.1038/s41590-019-0398-x PubMed

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  • 13.

    Reis-Neto ETD, Seguro LPC, Sato EI, Borba EF, Klumb EM, Costallat LTL, et al.: II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment. Adv Rheumatol 64: 48, 2024 10.1186/s42358-024-00386-8 PubMed

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  • 14.

    Schrezenmeier E, Dörner T: Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology. Nat Rev Rheumatol 16: 155166, 2020 10.1038/s41584-020-0372-x PubMed

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  • 15.

    Gheet FS, Dawoud HES, El-Shahaby WA, Elrifaey SM, Abdelnabi HH: Hydroxychloroquine in children with proliferative lupus nephritis: A randomized clinical trial. Eur J Pediatr 182: 16851695, 2023 10.1007/s00431-023-04837-0 PubMed

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  • 16.

    Peña-Vizcarra ÓR, Zavala-Miranda MF, Juárez-Cuevas B, Márquez-Macedo SE, Hernández-Andrade A, Nordmann-Gomes A, et al.: Effect of antimalarials on clinical outcomes in lupus nephritis. Rheumatology (Oxford) 63: 22302238, 2024 10.1093/rheumatology/kead576 PubMed

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  • 17.

    Gomez A, Jägerback S, Sjöwall C, Parodis I: Belimumab and antimalarials combined against renal flares in patients treated for extra-renal systemic lupus erythematosus: Results from 4 phase III clinical trials. Rheumatology (Oxford) 63: 338348, 2024 10.1093/rheumatology/kead253 PubMed

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  • 18.

    Marmor MF, Kellner U, Lai TYY, Lyons JS, Mieler WF, American Academy of Ophthalmology: Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 118: 415422, 2011 10.1016/j.ophtha.2010.11.017 PubMed

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  • 19.

    Dall’Era M, Solomons N, Federico R, Truman M: Comparison of standard of care treatment with a low steroid and mycophenolate mofetil regimen for lupus nephritis in the ALMS and AURA studies. Lupus 28: 591596, 2019 10.1177/0961203319842924 PubMed

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  • 20.

    Figueroa‐Parra G, Cuéllar‐Gutiérrez MC, González‐Treviño M, Sanchez‐Rodriguez A, Flores‐Gouyonnet J, Meade‐Aguilar JA, et al.: Impact of glucocorticoid dose on complete response, serious infections, and mortality during the initial therapy of lupus nephritis: A systematic review and meta‐analysis of the control arms of randomized controlled trials. Arthritis Rheumatology 76: 14081418, 2024 10.1002/art.42920 PubMed

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  • 21.

    Touma Z, Kayaniyil S, Parackal A, Bonilla D, Su J, Qian C, et al.: Unfavorable outcomes associated with glucocorticoid use in current standard-of-care management of systemic lupus erythematosus in Canada. ACR Open Rheumatol 6: 531539, 2024 10.1002/acr2.11680 PubMed

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  • 22.

    Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, et al.: Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 135: 248257, 2001 10.7326/0003-4819-135-4-200108210-00009 PubMed

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  • 23.

    Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, de Ramon Garrido E, Danieli MG, 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 46: 21212131, 2002 10.1002/art.10461 PubMed

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  • 24.

    Tamirou F, Nieuwland Husson S, Gruson D, Debiève F, Lauwerys BR, Houssiau FA, et al.: The low-dose intravenous cyclophosphamide Euro-Lupus regimen does not impact the ovarian reserve, as measured by serum anti-Müllerian hormone levels. J Am Soc Nephrol 69: 12671271, 2017 PubMed

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  • 25.

    Appel GB, Contreras G, Dooley MA: Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20: 11031112, 2009 10.1681/ASN.2008101028 PubMed

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  • 26.

    Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, et al.: Influence of race/ethnicity on response to lupus nephritis treatment: The ALMS study. Rheumatology (Oxford) 49: 128140, 2010 10.1093/rheumatology/kep346 PubMed

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  • 27.

    Liu Z, Zhang H, Liu Z, Xing C, Fu P, Ni Z, et al.: Multitarget therapy for induction treatment of lupus nephritis. Ann Intern Med 162: 1826, 2015 10.7326/M14-1030 PubMed

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  • 28.

    Rovin BH, Solomons N, Pendergraft WF, Dooley MA, Tumlin J, Romero-Diaz J, et al.; AURA-LV Study Group: A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney Int 95: 219231, 2019 10.1016/j.kint.2018.08.025 PubMed

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  • 29.

    Rovin BH, Teng YKO, Ginzler EM, Arriens C, Caster DJ, Romero-Diaz J, 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 397: 20702080, 2021 10.1016/S0140-6736(21)00578-X PubMed

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  • 30.

    Menn-Josephy H, Hodge LS, Birardi V, Leher H: Efficacy of voclosporin in proliferative lupus nephritis with high levels of proteinuria. Clin J Am Soc Nephrol 19: 309318, 2024 10.2215/CJN.0000000000000297 PubMed

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  • 31.

    Saxena A, Ginzler EM, Gibson K, Satirapoj B, Santillán AEZ, Levchenko O, et al.: Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 AURORA 2 clinical trial. Arthritis Rheumatol 76: 5967, 2024 10.1002/art.42657 PubMed

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  • 32.

    Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, et al.: Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 383: 11171128, 2020 10.1056/NEJMoa2001180 PubMed

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  • 33.

    Rovin BH, Furie R, Teng YKO, Contreras G, Malvar A, Yu X, 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 101: 403413, 2022 10.1016/j.kint.2021.08.027 PubMed

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  • 34.

    Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, et al.: Sequential therapies for proliferative lupus nephritis. N Engl J Med 350: 971980, 2004 10.1056/NEJMoa031855 PubMed

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  • 35.

    Anders HJ, Lei Y, Rovin BH: Induction and maintenance therapy of lupus nephritis: An obituary. Kidney Int 99: 288291, 2021 10.1016/j.kint.2020.11.009 PubMed

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  • 36.

    Houssiau FA, D’Cruz D, Sangle S, Remy P, Vasconcelos C, Petrovic R, et al.; MAINTAIN Nephritis Trial Group: Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: Results from the MAINTAIN Nephritis Trial. Ann Rheum Dis 69: 20832089, 2010 10.1136/ard.2010.131995 PubMed

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  • 37.

    Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, et al.; ALMS Group: Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med 365: 18861895, 2011 10.1056/NEJMoa1014460 PubMed

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  • 38.

    Jourde-Chiche N, Costedoat-Chalumeau N, Baumstarck K, Loundou A, Bouillet L, Burtey S, et al.; WIN-Lupus study group: Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): Results of a multicentre randomised controlled trial. Ann Rheum Dis 81: 14201427, 2022 10.1136/annrheumdis-2022-222435 PubMed

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  • 39.

    Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, et al.: B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: A randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 81: 100107, 2022 10.1136/annrheumdis-2021-220920 PubMed

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  • 40.

    Rovin BH, Furie RA, Ross Terres JA, Giang S, Schindler T, Turchetta A, et al.: Kidney outcomes and preservation of kidney function with obinutuzumab in patients with lupus nephritis: A post hoc analysis of the NOBILITY trial. Arthritis Rheumatol 76: 247254, 2024 10.1002/ART.42734 PubMed

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  • 41.

    Jayne D, Rovin B, Mysler EF, Furie RA, Houssiau FA, Trasieva T, et al.: Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis 81: 496506, 2022 10.1136/annrheumdis-2021-221478 PubMed

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  • 42.

    Mackensen A, Müller F, Mougiakakos D, Böltz S, Wilhelm A, Aigner M, et al.: Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 28: 21242132, 2022 10.1038/s41591-022-02017-5 PubMed

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  • 43.

    Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, et al.: CD19 CAR T-cell therapy in autoimmune disease — A case series with follow-up. N Engl J Med 390: 687700, 2024 10.1056/NEJMoa2308917 PubMed

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  • 44.

    Nordmann-Gomes A, Cojuc-Konigsberg G, Hernández-Andrade A, Navarro-Sánchez V, Ramírez-Sandoval JC, Rovin B, et al.: Lupus nephritis randomised controlled trials: evidence gaps and under-represented groups. Lupus Sci Med 11: e001331, 2024 10.1136/lupus-2024-001331 PubMed

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  • 45.

    Dall’Era M, Levesque V, Solomons N, Truman M, Wofsy D: Identification of clinical and serological factors during induction treatment of lupus nephritis that are associated with renal outcome. Lupus Sci Med 2: e000089, 2015 10.1136/lupus-2015-000089 PubMed

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  • 46.

    Mackay M, Dall’Era M, Fishbein J, Kalunian K, Lesser M, Sanchez-Guerrero J, et al.: Establishing surrogate kidney end points for lupus nephritis clinical trials: Development and validation of a novel approach to predict future kidney outcomes. Arthritis Rheumatol 71: 411419, 2019 10.1002/art.40724 PubMed

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  • 47.

    Malvar A, Pirruccio P, Alberton V, Lococo B, Recalde C, Fazini B, et al.: Histologic versus clinical remission in proliferative lupus nephritis. Nephrol Dial Transplant 32: 13381344, 2017 10.1093/ndt/gfv296 PubMed

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  • 48.

    Perez-Arias AA, Márquez-Macedo SE, Pena-Vizcarra OR, Zavala-Miranda MF, Romero-Díaz J, Morales-Buenrostro LE, et al.: The influence of repeated flares in response to therapy and prognosis in lupus nephritis. Nephrol Dial Transplant 38: 884893, 2023 10.1093/ndt/gfac304 PubMed

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  • 49.

    Mejia-Vilet JM, Malvar A, Arazi A, Rovin BH: The lupus nephritis management renaissance. Kidney Int 101: 242255, 2022 10.1016/j.kint.2021.09.012 PubMed

  • 50.

    Margery-Muir AA, Wetherall JD, Castley ASL, Hew M, Whidborne RS, Mallon DFJ, et al.: Establishment of gene copy number–specific normal ranges for serum C4 and its utility for interpretation in patients with chronically low serum C4 concentrations. Arthritis Rheumatol 66: 25122520, 2014 10.1002/art.38680 PubMed

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  • 51.

    Rodriguez-Ramirez S, Wiegley N, Mejia-Vilet JM: Kidney biopsy in management of lupus nephritis: A case-based narrative review. Kidney Med 6: 100772, 2024 10.1016/j.xkme.2023.100772 PubMed

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  • 52.

    Parodis I, Adamichou C, Aydin S, Gomez A, Demoulin N, Weinmann-Menke J, et al.: Per-protocol repeat kidney biopsy portends relapse and long-term outcome in incident cases of proliferative lupus nephritis. Rheumatology (Oxford) 59: 34243434, 2020 10.1093/rheumatology/keaa129 PubMed

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  • 53.

    Malvar A, Alberton V, Lococo B, Ferrari M, Delgado P, Nagaraja HN, et al.: Kidney biopsy–based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int 97: 156162, 2020 10.1016/j.kint.2019.07.018 PubMed

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  • 54.

    Zavala-Miranda MF, Sobrino-Vargas AM, Hernández-Andrade A, Caballero-Malacara V, Pérez-Arias AA, Márquez-Macedo SE, et al.: Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: A retrospective cohort study. Clin Rheumatol 43: 25332540, 2024 10.1007/s10067-024-07043-x PubMed

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  • 55.

    Rovin BH, Caster DJ, Cattran DC, Gibson KL, Hogan JJ, Moeller MJ, et al.; Conference Participants: Management and treatment of glomerular diseases (part 2): Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int 95: 281295, 2019 10.1016/j.kint.2018.11.008 PubMed

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  • 56.

    Arora S, Rovin BH: Expert perspective: An approach to refractory lupus nephritis. Arthritis Rheumatol 74: 915926, 2022 10.1002/art.42092 PubMed

  • 57.

    Crickx E, Tamirou F, Huscenot T, Costedoat-Chalumeau N, Rabant M, Karras A, et al.: Molecular signatures of kidney antibody–secreting cells in lupus patients with active nephritis upon immunosuppressive therapy. Arthritis Rheumatol 73: 14611466, 2021 10.1002/art.41703 PubMed

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  • 58.

    Roccatello D, Fenoglio R, Caniggia I, Kamgaing J, Naretto C, Cecchi I, et al.: Daratumumab monotherapy for refractory lupus nephritis. Nat Med 29: 20412047, 2023 10.1038/s41591-023-02479-1 PubMed

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  • 59.

    Frangou E, Anders H-J, Bajema IM, Teng YKO, Malvar A, Rovin BH, et al.: Immunosuppression withdrawal in patients with lupus nephritis. J Am Soc Nephrol 35: 955958, 2024 10.1681/ASN.0000000000000365 PubMed

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  • 60.

    Panagiotopoulos A, Kapsia E, El Michelakis I, Boletis J, Marinaki S, Sfikakis PP, et al.: Immunosuppressives discontinuation after renal response in lupus nephritis: Predictors of flares, time to withdrawal and long-term outcomes [published online ahead of print Jul 22, 2024]. Rheumatology (Oxford) doi:10.1093/rheumatology/keae381 PubMed

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  • 61.

    Caravaca-Fontán F, Stevens K, Padrón M, Huerta A, Montomoli M, Villa J, et al.: Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis. Nephrol Dial Transplant 39: 328340, 2024 10.1093/ndt/gfad175 PubMed

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  • 62.

    Yen FS, Wang SI, Hsu CC, Hwu CM, Wei JCC: Sodium-glucose cotransporter-2 inhibitors and nephritis among patients with systemic lupus erythematosus. JAMA Netw Open 7: e2416578, 2024 10.1001/jamanetworkopen.2024.16578 PubMed

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  • 63.

    Piccoli GB, Attini R, Torreggiani M, Chatrenet A, Manzione AM, Masturzo B, et al.: Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome. Kidney Int 105: 865876, 2024 10.1016/j.kint.2023.12.018 PubMed

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  • 64.

    Wind M, Fierro JJ, Bloemenkamp KWM, de Leeuw K, Lely AT, Limper M, et al.: Pregnancy outcome predictors in systemic lupus erythematosus: A systematic review and meta-analysis. Lancet Rheumatol 6: e667e683, 2024 10.1016/S2665-9913(24)00160-7 PubMed

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  • 65.

    Tarter L, Bermas BL: Expert perspective on a clinical challenge: Lupus and pregnancy. Arthritis Rheumatol 76: 321331, 2024 10.1002/art.42756 PubMed

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    Buyon JP, Kim MY, Guerra MM, Lu S, Reeves E, Petri M, et al.: Kidney outcomes and risk factors for nephritis (flare/de novo) in a multiethnic cohort of pregnant patients with lupus. Clin J Am Soc Nephrol 12: 940946, 2017 10.2215/CJN.11431116 PubMed

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  • 67.

    Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, et al.; BSR Standards, Audit and Guidelines Working Group: British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: Immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 62: e48e88, 2023 10.1093/rheumatology/keac551 PubMed

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  • 68.

    Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, et al.: 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 72: 529556, 2020 10.1002/art.41191 PubMed

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  • 69.

    Park S, Lee SM, Park JS, Hong J-S, Chin HJ, Na KY, et al.: Midterm eGFR and adverse pregnancy outcomes: The clinical significance of gestational hyperfiltration. Clin J Am Soc Nephrol 12: 10481056, 2017 10.2215/CJN.12101116 PubMed

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  • 70.

    Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT: Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 80: 1425, 2021 10.1136/annrheumdis-2020-218272 PubMed

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  • 71.

    Ishizaki J, Saito K, Nawata M, Mizuno Y, Tokunaga M, Sawamukai N, et al.: Low complements and high titre of anti-Sm antibody as predictors of histopathologically proven silent lupus nephritis without abnormal urinalysis in patients with systemic lupus erythematosus. Rheumatology (Oxford) 54: 405412, 2015 10.1093/rheumatology/keu343 PubMed

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  • 72.

    Parikh SV, Malvar A, Song H, Alberton V, Lococo B, Vance J, et al.: Characterising the immune profile of the kidney biopsy at lupus nephritis flare differentiates early treatment responders from non-responders. Lupus Sci Med 2: e000112, 2015 10.1136/lupus-2015-000112 PubMed

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  • 73.

    Stevens PE, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, et al.: KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 105: S117S314, 2024 10.1016/j.kint.2023.10.018 PubMed

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