Position Statement and Consensus Recommendation of the Immunonephrology Working Group of the Portuguese Society of Nephrology on the Management of Proliferative Lupus Nephritis and the Use of Old and Emergent Combination Therapies
DOI:
https://doi.org/10.71749/pkj.139Keywords:
Immunosuppressive Agents/therapeutic use, Lupus Erythematosus, Systemic, Lupus Nephritis, Practice GuidelineAbstract
Lupus nephritis is an immune complex mediated glomerulonephritis representing one of the most severe manifestations of systemic lupus erythematosus. Despite advances in therapy, progression to chronic kidney disease remains significantly high, underlining the need for more effective drug regimens that encompass less long-term toxicity. Recently, lupus nephritis has been reframed as a form of chronic kidney disease, shifting therapeutic goals toward three main pillars: sustained immunological control with prevention of relapse, interventions that target non-immune factors of chronic kidney disease and strategies that minimize infection risk. The emergence of novel therapeutic agents has prompted updates of major international guidelines, with new combination drug schemes that increase efficacy and allow glucocorticoid sparing. This position statement reviews the KDIGO 2024, ACR 2024, and EULAR 2025 recommendations and presents the Immunophenology Working Group of the Portuguese Society of Nephrology perspective on the management of proliferative Lupus nephritis - Classes III and IV, according to our national context.
Downloads
References
Hanly JG, O’Keeffe AG, Su L, Urowitz MB, Romero‑Diaz J, Gordon C, et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology. 2016;55:252‑62. doi: 10.1093/rheumatology/kev311.
Kidney Disease: Improving Global Outcomes (KDIGO) Lupus Nephritis Work Group. KDIGO 2024 Clinical Practice Guideline for the management of LUPUS NEPHRITIS. Kidney Int. 2024;105:S1‑S69. doi: 10.1016/j.kint.2023.09.002.
Luo W, Farinha F, Isenberg DA, Rahman A. Survival analysis of mortality and development of lupus nephritis in patients with systemic lupus erythematosus up to 40 years of follow‑up. Rheumatology. 2022;62:200‑8. doi: 10.1093/rheumatology/keac218.
Farinha F, Barreira S, Couto M, Cunha M, Fonseca D, Freitas R, et al. Risk of chronic kidney disease in 260 patients with lupus nephritis: analysis of a nationwide multicentre cohort with up to 35 years of follow‑up. Rheumatology. 2025;64:1201‑9. doi: 10.1093/rheumatology/keae236.
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;68:1432‑41. doi: 10.1002/art.39594.
Anders HJ. A farewell to the concept of induction and maintenance therapy of lupus nephritis. ERA Nephrology Education Portal Newsletter May 2023 [accessed Dec 2025] Available at: https://www.era‑online.org/nep‑newsletters/
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105:S117‑S314. doi: 10.1016/j.kint.2023.10.018.
Fanouriakis A, Kostopoulou M, Anders HJ, Andersen J, Aringer M, Beresford MW, et al. EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update. Ann Rheum Dis. 2026;85:75‑90. doi: 10.1016/j.ard.2025.09.007.
Sammaritano LR, Askanase A, Bermas BL, Dall’Era M, Duarte‑García A, Hiraki LT, et al. 2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis. Arthritis Care Res. 2025;77:1045‑65. doi: 10.1002/acr.25528.
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. 2020;97:156‑62. doi: 10.1016/j.kint.2019.07.018.
Chehab G, Sauer GM, Richter JG, Brinks R, Willers R, Fischer‑Betz R, Winkler‑Rohlfing B, Schneider M. Medical adherence in patients with systemic lupus erythematosus in Germany: predictors and reasons for non‑adherence ‑ a cross‑sectional analysis of the LuLa‑cohort. Lupus. 2018;27:1652‑60. doi: 10.1177/0961203318785245.
Faria DA, Revoredo LS, Vilar MJ, Eulália Maria Chaves M. Resilience and treatment adhesion in patients with systemic lupus erythematosus. Open Rheumatol J. 2014;8:1‑8. doi: 10.2174/1874312920140127001.
Emamikia S, Gentline C, Enman Y, Parodis I. How Can We Enhance Adherence to Medications in Patients with Systemic Lupus Erythematosus? Results from a Qualitative Study. J Clin Med. 2022;11:1857. doi: 10.3390/jcm11071857.
Dima A, Jurcut C, Chasset F, Felten R, Arnaud L. Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge. Ther Adv Musculoskelet Dis. 2022;14:1759720X211073001. doi: 10.1177/1759720X211073001.
Chasset F, Francès C, Barete S, Amoura Z, Arnaud L. Influence of smoking on the efficacy of antimalarials in cutaneous lupus: a meta‑analysis of the literature. J Am Acad Dermatol. 2015;72:634‑9. doi: 10.1016/j.jaad.2014.12.025. Erratum in: J Am Acad Dermatol. 2015;73:353.
Mahr A, Heijl C, Le Guenno G, Faurschou M. ANCA‑associated vasculitis and malignancy: current evidence for cause and consequence relationships. Best Pract Res Clin Rheumatol. 2013;27:45‑56. doi: 10.1016/j.berh.2012.12.003.
Koyama H, Wada T, Nishizawa Y, Iwanaga T, Aoki Y. Cyclophosphamide‑induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer. 1977;39:1403‑9. doi:10.1002/1097‑0142(197704)39:4<1403::aid‑cncr2820390408>3.0.co;2‑8.
Luong SN, Isaacs A, Liu Z, Sin FE, Giles I. A systematic review and meta‑analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child‑bearing age with autoimmune rheumatic disease. Expert Rev Clin Immunol. 2020;16:321‑33. doi: 10.1080/1744666X.2020.1724091.
Rivkees SA, Crawford JD. The relationship of gonadal activity and chemotherapy‑induced gonadal damage. JAMA. 1988;259:2123‑5.
Watson AR, Rance CP, Bain J. Long term effects of cyclophosphamide on testicular function. Br Med J. 1985;291:1457‑60. doi: 10.1136/bmj.291.6507.1457.
Fairley KF, Barrie JU, Johnson W. Sterility and testicular atrophy related to cyclophosphamide therapy. Lancet. 1972;1:568-9. doi:10.1016/s0140-6736(72)90358-3.
Steinberg AD, Kaltreider HB, Staples PJ, Goetzl EJ, Tala N, Decker JL. Cyclophosphamide in lupus nephritis: a controlled trial. Ann Intern Med. 1971;75:165-71. doi: 10.7326/0003-4819-75-2-165.
Steinberg AD, Decker JL. A double-blind controlled trial comparing cyclophosphamide, azathioprine and placebo in the treatment of lupus glomerulonephritis. Arthritis Rheum. 1974;17:923-37. doi:10.1002/art.1780170602.
Decker JL, Klippel JH, Plotz PH, Steinberg AD. Cyclophosphamide or azathioprine in lupus glomerulonephritis. A controlled trial: results at 28 months. Ann Intern Med. 1975;83:606-15. doi:10.7326/0003-4819-83-5-606.
Austin HA 3rd, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986;314:614-9. doi:10.1056/NEJM198603063141004.
Steinberg AD. The treatment of lupus nephritis. Kidney Int. 1986;30:769-87. doi:10.1038/ki.1986.254.
Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996;125:549-57. doi:10.7326/0003-4819-125-7-199610010-00003.
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. 2001;135:248-57. doi:10.7326/0003-4819-135-4-200108210-00009.
Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, 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. 2002;46:2121-31. doi:10.1002/art.10461.
Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, de Ramon Garrido E, Danieli MG, 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;69:61-4. doi:10.1136/ard.2008.102533.
Anca D Askanase, Margie Byron, Lynette L Keyes-Elstein, Patricia C Cagnoli, W Joseph McCune, W Winn Chatham, et al. Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis Rheumatol. 2014;66:3096-104. doi:10.1002/art.38790.
Rathi M, Goyal A, Jaryal A, Sharma A, Gupta PK, Ramachandran R, Kumar V, et al. Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int. 2016;89:235-42. doi:10.1038/ki.2015.318.
Rovin BH, Parikh SV, Hebert LA, Chan TM, Mok CC, Ginzler EM, et al. Lupus nephritis: induction therapy in severe lupus nephritis-should MMF be considered the drug of choice? Clin J Am Soc Nephrol. 2013;8:147-53. doi:10.2215/CJN.03290412.
Walsh M, Solomons N, Lisk L, Jayne DR. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis with poor kidney function: a subgroup analysis of the Aspreva Lupus Management Study. Am J Kidney Dis. 2013;61:710-5. doi:10.1053/j.ajkd.2012.11.042.
Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47:85-118. doi:10.1016/s0162-3109(00)00188-0.
Seo P. Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases. UpToDate. [accessed Dec 2025] Available at: https://www.uptodate.com/contents/mycophenolate-overview-of-use-and-adverse-effects-in-the-treatment-of-rheumatic-diseases
Pourafshar N, Karimi A, Wen X, Sobel E, Pourafshar S, Agrawal N, et al. The utility of trough mycophenolic acid levels for the management of lupus nephritis. Nephrol Dial Transplant. 2019;34:83-9. doi: 10.1093/ndt/gfy026.
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. 2022;81:100-7. doi: 10.1136/annrheumdis-2021-220920.
Furie RA, Rovin BH, Garg JP, Santiago MB, Aroca-Martinez G, Zuta Santillan AE, et al; REGENCY Trial Investigators. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med. 2025;392:1471-83. doi: 10.1056/NEJMoa2410965.
Induction Therapy for Lupus Nephritis With no Added Oral Steroids: A Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF (OBILUP) NCT04702256.
Parodis I, Stockfelt M, Sjövall C. B Cell Therapy in Systemic Lupus Erythematosus: From Rationale to Clinical Practice. Front Med. 2020;7:316. doi: 10.3389/fmed.2020.00316.
Resumo das Características do Medicamento [accessed Dec 2025] Available at: https://ec.europa.eu/health/documents/community-register/2017/20170320137420/anx_137420_pt.pdf
Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al; BLISS-52 Study Group. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:721-31. doi: 10.1016/S0140-6736(10)61354-2.
Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzová D, et al; BLISS-76 Study Group. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918-30. doi: 10.1002/art.30613.
Iaccarino L, Bettio S, Reggia R, Zen M, Frassi M, Andreoli L, et al. Effects of Belimumab on Flare Rate and Expected Damage Progression in Patients With Active Systemic Lupus Erythematosus. Arthritis Care Res. 2017;69:115-23. doi: 10.1002/acr.22971.
Fanouriakis A, Adamichou C, Koutsoviti S, Panopoulos S, Staveri C, Klagou A, et al. Low disease activity-irrespective of serologic status at baseline-associated with reduction of corticosteroid dose and number of flares in patients with systemic lupus erythematosus treated with belimumab: A real-life observational study. Semin Arthritis Rheum. 2018;48:467-74. doi: 10.1016/j.semarthrit.2018.02.014.
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. 2020;383:1117-28. doi: 10.1056/NEJMoa2001180.
Anders HJ, Furie R, Malvar A, Zhao MH, Hiromura K, Weinmann-Menke J, et al. Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial. Nephrol Dial Transplant. 2023;38:2733-42. doi: 10.1093/ndt/gfad167
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. 2022;101:403-13. doi: 10.1016/j.kint.2021.08.027.
Malvar A, Alberton V, Recalde C, Heguilen R. Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A "post-hoc" analysis of participants in the BLISS-LN and open label extension study belonging to a single center. Lupus. 2023;32:1394-401. doi: 10.1177/09612033231204070.
Furie R, Rovin BH, Houssiau F, Contreras G, Teng YK, Curtis P, Green Y, Okily M, Madan A, Roth DA. Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study. Clin J Am Soc Nephrol. 2022;17:1620-30. doi: 10.2215/CJN.02520322.
Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, 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;79:713-23. doi: 10.1136/annrheumdis-2020-216924.
Wang M, Zhou J, Niu Q, Wang H. Mechanism of tacrolimus in the treatment of lupus nephritis. Front Pharmacol. 2024;15:1331800. doi: 10.3389/fphar.2024.1331800.
van Gelder T, Lerma E, Engelke K, Huizinga RB. Voclosporin: a novel calcineurin inhibitor for the treatment of lupus nephritis. Expert Rev Clin Pharmacol. 2022;15:515-29. doi: 10.1080/17512433.2022.2092470.
Kale A, Shelke V, Lei Y, Gaikwad AB, Anders HJ. Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis. Cells. 2023;12:2440. doi: 10.3390/cells12202440.
Deng J, Luo L, Zhu L, Xie H. Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials. Turk J Med Sci. 2018;48:901-10. doi: 10.3906/sag-1804-57.
Zhou T, Zhang X, Lin W, Lin S. Multitarget Therapy: An Effective and Safe Therapeutic Regimen for Lupus Nephritis. J Pharm Pharm Sci. 2019;22:365-75. doi: 10.18433/jpps30526.
Yap DY, Li PH, Tang C, So BY, Kwan LP, Chan GC, et al. Long-Term Results of Triple Immunosuppression With Tacrolimus Added to Mycophenolate and Corticosteroids in the Treatment of Lupus Nephritis. Kidney Int Rep. 2021;7:516-25. doi: 10.1016/j.ekir.2021.12.005.
Rovin BH, Solomons N, Pendergraft WF 3rd, 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. 2019;95:219-31. doi: 10.1016/j.kint.2018.08.025
Rovin BH, Teng YK, 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. 2021;397:2070-80. doi: 10.1016/S0140-6736(21)00578-X
Arriens C, Teng YK, Ginzler EM, Parikh SV, Askanase AD, Saxena A, et al. Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis. Arthritis Care Res. 2023;75:1399-408. doi: 10.1002/acr.25007.
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. 2024;76:59-67. doi: 10.1002/art.42657.
Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83:15-29. doi: 10.1136/ard-2023-224762.
Product Information. Gazyva (obinutuzumab). Genentech, 2022, SUPPL-34.
Shah A. Obinutuzumab: a novel anti-CD20 monoclonal antibody for previously untreated chronic lymphocytic leukemia. Ann Pharmacother. 2014;48:1356-61. doi: 10.1177/1060028014543271.
Mak JW, Law AW, Law KW, Ho R, Cheung CK, Law MF. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era. World J Gastroenterol. 2023;29:4942-61. doi: 10.3748/wjg.v29.i33.4942.
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. 2024;76:247-54. doi: 10.1002/art.42734.
Arnold J, Dass S, Twigg S, Jones CH, Rhodes B, Hewins P, et al. Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab. Rheumatology. 2022;61:4905-9. doi: 10.1093/rheumatology/keac150.
Induction Therapy for Lupus Nephritis With no Added Oral Steroids: A Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF (OBILUP) ClinicalTrials.gov ID NCT04702256.
Singh T, Gomez S, Panzer SE, Ferguson SK, Garg S. Obinutuzumab for Treatment of Refractory Lupus Nephritis: TH-PO638. J Am Soc Nephrol. 2024;35:10.1681/ASN.2024b6aq3vkk. doi: 10.1681/ASN.2024b6aq3vkk.
Teoh STY, Yap DYH, Chan TM. Obinutuzumab in patients with repeated lupus nephritis flares: A case series. Lupus. 2025;34:545-8. doi: 10.1177/09612033251327170.
U.S. Food and Drug Administration. GAZYVA® [accessed Dec 2025] Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125486s037s038lbl.pdf
European Medicines Agency. Gazyva [accessed Dec 2025] Available at: https://www.ema.europa.eu/en/documents/product-information/gazyva-epar-product-information_en.pdf
Mejia-Vilet JM, Ayoub I. The Use of Glucocorticoids in Lupus Nephritis: New Pathways for an Old Drug. Front Med. 2021;8:622225. doi: 10.3389/fmed.2021.622225.
Badsha H, Kong KO, Lian TY, Chan SP, Edwards CJ, Chng HH. Low-dose pulse methylprednisolone for systemic lupus erythematosus flares is efficacious and has a decreased risk of infectious complications. Lupus. 2002;11:508-13. doi: 10.1191/0961203302lu243oa.
Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Semin Arthritis Rheum. 2003;32:370-7. doi: 10.1053/sarh.2002.50003.
Buttgezeit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61:718-22. doi: 10.1136/ard.61.8.718.
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. 2017;32:1338-44. doi: 10.1093/ndt/gfv296.
Frangou E, Anders HJ, Bajema IM, Teng YK, Malvar A, Rovin BH, et al. Immunosuppression Withdrawal in Patients with Lupus Nephritis: When, How, and for Whom Will It Be Safe? (incomplete reference as per document)
Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017;12:825-35. doi: 10.2215/CJN.05780616.
Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020;6:7. doi: 10.1038/s41572-019-0141-9
Rojas-Rivera JE, Bakkaloglu SA, Bolignano D, Nistor I, Sarafidis PA, Stoumpos S, et al. Chronic kidney disease: the missing concept in the 2019 EULAR/ERA-EDTA recommendations for lupus nephritis. Nephrol Dial Transplant. 2023;39:151-8. doi: 10.1093/ndt/gfad154.
Fanouriakis A, Kostopoulou M, Andersen J, Aringer M, Arnaud L, Bae SC, Boletis J, et al. EULAR recommendations for the management of systemic lupus erythematosus. 2023 update. Ann Rheum Dis. 2024;83:15-29. doi: 10.1136/ard-2023-224762.
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. 2012;64:797-808. doi: 10.1002/acr.21664.
Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. Ann Intern Med. 2001;135:73-87. doi: 10.7326/0003-4819-135-2-200107170-00007. Erratum in: Ann Intern Med 2002;137:299.
Linda F. Fried, Nicholas Emanuele, Jane H. Zhang, Mary Brophy, Todd A. Conner, et al. Combined angiotensin inhibition for diabetic nephropathy. N Engl J Med. 2013;369(20):1892-1903.
Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349:2399-406. doi: 10.1056/NEJMoa035471.
Tselios K, Gladman DD, Su J, Ace O, Urowitz MB. Evolution of Risk Factors for Atherosclerotic Cardiovascular Events in Systemic Lupus Erythematosus: A Longterm Prospective Study. J Rheumatol. 2017;44:1841-9. doi: 10.3899/jrheum.161121.
Al Sawah S, Zhang X, Zhu B, Magder LS, Foster SA, Petri M, et al. Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus- the Hopkins Lupus Cohort. Lupus Sci Med. 2015;2:e000066. doi: 10.1136/lupus-2014-000066.
Heerspink HJ, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383:1436-46. doi: 10.1056/NEJMoa2024816.
Kronbichler A. Sodium-glucose cotransporter 2 (SGLT2) inhibition and autoimmunity. Semin Arthritis Rheum. 2025;72S:152663. doi: 10.1016/j.semarthrit.2025.152663.
Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006;54:2550-7. doi: 10.1002/art.21955.
Ruiz-Irastorza G, Egurbide MV, Pijoan JI, Garmendia M, Villar I, Martinez-Berriotxoa A, et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus. 2006;15:577-83. doi: 10.1177/0961203306071872.
Li BM, Hung JH, Yang PC, Lin SJ, Lai EC, Weng MY. Weighing dose-related benefits and risks of hydroxychloroquine treatment in systemic lupus erythematosus patients. Arthritis Rheumatol. 2025. doi: 10.1002/art.70022.
Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet. 1999;354:359-64. doi: 10.1016/S0140-6736(98)10363-X.
The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388:117-27. doi: 10.1056/NEJMoa2204233.
Luo T, Zhang L, Tu K, Li G, Su H, Gong G, et al. SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges. Front Immunol. 2025;16:1589341. doi: 10.3389/fimmu.2025.1589341.
Nishiyama A. Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease. Hypertens Res. 2019;42:293-300. doi: 10.1038/s41440-018-0158-6.
Sun M, Xiao F, Chen X, Wang L, Dai H. Finerenone as a Nonsteroidal Mineralocorticoid Receptor Antagonist for Lupus Nephritis. Kidney Int Rep. 2025;10:3694-5. doi: 10.1016/j.ekir.2025.07.039.
Blaess J, Geneton S, Goepfert T, Appenzeller S, Bordier G, Davergne T, et al. Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force. RMD Open. 2024;10:e004171. doi: 10.1136/rmdopen-2024-004171.
Blaess J, Geneton S, Goepfert T, Appenzeller S, Bordier G, Davergne T, et al. Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force. RMD Open. 2024;10:e004171. doi: 10.1136/rmdopen-2024-004171.
Wilund KR, Thompson S, Viana JL, Wang AY. Physical activity and Health in Chronic Kidney Disease. Contrib Nephrol. 2021;199:43-55. doi: 10.1159/000517696.
Bishop NC, Burton JO, Graham-Brown MPM, Stensel DJ, Viana JL, Watson EL. Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits. Nat Rev Nephrol. 2023;19:244-56. doi: 10.1038/s41581-022-00675-9.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Estela Nogueira, Inês Ferreira, Iolanda Godinho, Sofia Oliveira Correia, Alice Lança, Raquel Vaz, Helena Pinto, Ivo Laranjinha, Teresa Jerónimo, Clara Santos, António Inácio, Nuno Afonso
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
