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Askanase AD, Furie R, Dall'Era M, Bomback AS, Schwarting A, Zhao MH, Bruce IN, Khamashta M, Rubin B, Carroll A, Levy RA, van Vollenhoven R, Urowitz MB. Disease-Modifying Therapies in Lupus Nephritis: A Narrative Review Evaluating Currently Used Pharmacologic Agents. Rheumatol Ther 2025; 12:421-434. [PMID: 40186747 PMCID: PMC12084441 DOI: 10.1007/s40744-025-00752-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/12/2025] [Indexed: 04/07/2025] Open
Abstract
As more lupus nephritis (LN) medications become available, identifying treatments that are disease-modifying is critical in making treatment decisions. Based on our 2022 published working definition of LN disease modification as 'minimizing disease activity with the fewest treatment-associated toxicities and slowing progression to end-stage kidney disease' (ESKD), the objective of this review was to classify current LN treatments according to the proposed kidney disease modification criteria, excluding toxicities. Based upon a selection of LN clinical trial (n = 27) and observational study (n = 20) publications, as well as the authors' clinical experiences, we evaluated the disease modification potential for 16 LN treatments (inclusive of antimalarials, glucocorticoids, immunosuppressants, calcineurin inhibitors and biologics) according to the proposed kidney disease activity and organ damage criteria at year 1, years 2-5, and > 5-year time points. Fulfilling criteria at year 1 and years 2-5 was considered evidence for disease modification potential. Satisfying criteria at > 5 years (slowing or preventing progression in SLICC/ACR Damage Index [SDI] and ESKD, and/or doubling of serum creatinine) was used to confirm disease modification. Each treatment was designated as one of the following at each time point: (a) criterion met; (b) inconclusive; (c) no available supportive data. This review excluded an assessment of potential toxicities. All LN treatments met at least one of the potential kidney disease-modification criteria at any time point, but limited relevant data in the literature meant disease modification > 5 years could only be confirmed for cyclophosphamide. Belimumab met more criteria across the three time points than any other biologic treatment but lacked > 5-year data to confirm disease modification. Further research is needed to support the classification of LN treatments as disease modifiers, particularly for > 5 years. We discuss considerations for future studies, challenges to the classification, and possible updates to published criteria.
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Affiliation(s)
- Anca D Askanase
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Richard Furie
- Division of Rheumatology, Northwell Health, Great Neck, NY, USA
| | - Maria Dall'Era
- Division of Rheumatology, University of California San Francisco School of Medicine, San Francisco, CA, USA
| | - Andrew S Bomback
- Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Andreas Schwarting
- Rheumatology Center Rhineland Palatinate, Bad Kreuznach, Germany
- University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Ming-Hui Zhao
- Renal Division, Peking University First Hospital, Beijing, China
| | - Ian N Bruce
- The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | | | | | | | - Roger Abramino Levy
- Specialty Care, Global Medical Affairs, GSK, 1250 S Collegeville Rd, Collegeville, PA, 19426, USA.
| | - Ronald van Vollenhoven
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Murray B Urowitz
- Professor Emeritus, Department of Medicine, University of Toronto, Toronto, ON, Canada
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Dobrowolski C, Lao SM, Kharouf F, Croci PP, Wither J, Gladman DD, Garcia LW, Jauhal A, Touma Z. Lupus nephritis II: Treatment and monitoring. Adv Clin Chem 2025; 126:121-154. [PMID: 40185533 DOI: 10.1016/bs.acc.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2025]
Abstract
Renal involvement in systemic lupus erythematosus (SLE), lupus nephritis (LN), is common and can result in significant morbidity, including progressive renal dysfunction, and even ultimately leading to death. LN is heterogeneous complicated by the immunologic component, and it is critical to accurately classify LN to direct optimal therapy. Accordingly, identification of objective markers is paramount in reflecting disease stage and monitoring treatment response. In part two of this series, we comprehensively examine LN disease classification, therapies and potential markers to guide therapeutic options.
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Affiliation(s)
- Chrisanna Dobrowolski
- Division of Rheumatology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, United States
| | - Shu Min Lao
- Division of Rheumatology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, United States
| | - Fadi Kharouf
- Centre for Prognosis Studies in Rheumatic Diseases, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
| | - Paula Parnizari Croci
- Hospital Manuel Quintela, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Joan Wither
- Centre for Prognosis Studies in Rheumatic Diseases, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
| | - Dafna D Gladman
- Centre for Prognosis Studies in Rheumatic Diseases, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
| | - Laura Whitall Garcia
- Centre for Prognosis Studies in Rheumatic Diseases, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada
| | - Arenn Jauhal
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Zahi Touma
- Centre for Prognosis Studies in Rheumatic Diseases, University of Toronto Lupus Clinic, Toronto Western Hospital, Toronto, ON, Canada.
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Gezgin Yildirim D, Orulluoglu EY, Yildiz C, Acari C, Dundar HA, Akaci O, Akinci N, Aliyev E, Alpman BN, Altug Gucenmez O, Arslanoglu Aydin E, Atmis B, Avar Aydin PO, Aydin F, Baba O, Baglan E, Bagrul I, Barut K, Basaran O, Bayrakci US, Belder N, Yucel BB, Buyukkaragoz B, Caglayan S, Cakan M, Celikel E, Demir F, Demir S, Demir Yigit Y, Demirkan FG, Dincel N, Dogantan S, Ekici Tekin Z, Genc E, Haslak F, Isguder R, Kara A, Kasap Cuceoglu M, Kaya Akca U, Kisaoglu H, Kisla Ekinci RM, Kızıldag Z, Kurt T, Kucukali B, Leventoglu E, Nalcacioglu H, Yener GO, Ozdel S, Ozdemir Atikel Y, Ozdemir Cicek S, Pektas Leblebiciler S, Serdaroglu E, Sonmez HE, Sunar Yayla EN, Surmeli Doven S, Sahin S, Sener S, Tanatar A, Tanidir M, Taskin SN, Tiryaki B, Tuncez S, Turkucar S, Uzun Kenan B, Yildiz N, Yilmaz K, Tabel Y, Dursun I, Canpolat N, Mir S, Peru H, Topaloglu R, Kaya Gurgoze M, Balat A, Bilginer Y, Celikel Acar B, Sozeri B, Unsal E, Kasapcopur O, Bakkaloglu SA. Cyclophosphamide treatment with a comparison in both pediatric rheumatology and pediatric nephrology practices. Pediatr Rheumatol Online J 2025; 23:24. [PMID: 40069880 PMCID: PMC11895381 DOI: 10.1186/s12969-025-01080-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 03/03/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND Cyclophosphamide (CYC) is an inactive alkylating agent that transforms the alkyl radicals into other molecules and is used in combination with systemic corticosteroids in the treatment of many childhood rheumatic diseases, such as systemic lupus erythematosus (SLE), and ANCA-associated vasculitis (AAV). In recent years, rituximab (RTX), a B-cell-targeting anti-CD20 monoclonal antibody, has emerged as a new alternative treatment modality over CYC for induction therapy of childhood-onset rheumatic diseases. Clinicians adopt different practices for using CYC particularly in relation to indications, posology, pre-treatment laboratory work-up, post-treatment follow-up, and screening pre- and post-treatment vaccination status. This study aimed to evaluate the principles and approaches of administering CYC therapy in pediatric rheumatology and pediatric nephrology practices and to compare the clinician preferences for CYC and RTX in induction therapy of childhood-onset rheumatic diseases. METHODS This study includes a web-based questionnaire executed on 87 participants (56 pediatric rheumatologists (PRs) and 31 pediatric nephrologists (PNs)). Both pediatric subspecialties evaluated and compared the most common indications for CYC treatment, pre-treatment consent protocols, pre-and post-treatment laboratory tests, dosing strategies, and side effects. RESULTS Childhood-onset SLE (95%) and AAV (69%) were the most common diseases for which CYC treatment is used. All clinicians, except 2 PNs prescribed CYC via intravenous route. 61% of the PRs and 71% of PNs reported using a monthly dose of 500 mg/m² CYC for 6 months in accordance with the National Institutes of Health (NIH) protocol. All clinicians conducted pre-CYC treatment assessments of complete blood count and kidney function tests. Hepatitis B (82%), chickenpox (76%), and mumps-measles-rubella (72%) were the most frequently assessed vaccines. Adverse effects associated with CYC include cytopenia (86%), nausea (52%), liver toxicity (20%), hair loss (31%), hemorrhagic cystitis (37%), allergic reactions (16%), dyspnea (5%), and infertility (2%). 9 clinicians stated that they performed gonad-sparing interventions before CYC, which clarifies why CYC was more commonly preferred in the induction therapy of SLE and AAV over RTX by both PRs and PNs. CONCLUSIONS Clinicians still tend to choose CYC over RTX in induction therapy of SLE and AAV and mostly prefer the high-dose CYC treatment regimen suggested by the NIH.
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Affiliation(s)
- Deniz Gezgin Yildirim
- Department of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, 21000, Turkey.
| | | | - Cisem Yildiz
- Department of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, 21000, Turkey
| | - Ceyhun Acari
- Department of Pediatric Rheumatology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Hatice Adiguzel Dundar
- Department of Pediatric Rheumatology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
| | - Okan Akaci
- Department of Pediatric Nephrology, Bursa City Hospital, Bursa, Turkey
| | - Nurver Akinci
- Department of Pediatric Nephrology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Emil Aliyev
- Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | | | - Ozge Altug Gucenmez
- Department of Pediatric Rheumatology, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
| | | | - Bahriye Atmis
- Department of Pediatric Nephrology, Faculty of Medicine, Cukurova University, Adana, Turkey
| | | | - Fatma Aydin
- Department of Pediatric Rheumatology, Faculty of Medicine, Ankara University, Ankara, Turkey
| | - Ozge Baba
- Department of Pediatric Rheumatology, Van City Hospital, Van, Turkey
| | - Esra Baglan
- Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey
| | - Ilknur Bagrul
- Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
| | - Ozge Basaran
- Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Umut Selda Bayrakci
- Department of Pediatric Nephrology, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Nuran Belder
- Department of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, 21000, Turkey
| | - Burcu Bozkaya Yucel
- Department of Pediatric Rheumatology, Samsun Training and Research Hospital, Samsun, Turkey
| | - Bahar Buyukkaragoz
- Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Sengul Caglayan
- Department of Pediatric Rheumatology, Antalya City Hospital, Antalya, Turkey
| | - Mustafa Cakan
- Department of Pediatric Rheumatology, Zeynep Kamil Training and Research Hospital, Istanbul, Turkey
| | - Elif Celikel
- Department of Pediatric Rheumatology, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Ferhat Demir
- Department of Pediatric Rheumatology, Acıbadem Healthcare Group, Istanbul, Turkey
| | - Selcan Demir
- Department of Pediatric Rheumatology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey
| | - Yasemin Demir Yigit
- Department of Pediatric Rheumatology, Fırat University Faculty of Medicine, Elazig, Turkey
| | - Fatma Gul Demirkan
- Department of Pediatric Rheumatology, Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey
| | - Nida Dincel
- Department of Pediatric Nephrology, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
| | - Seyda Dogantan
- Department of Pediatric Rheumatology, Basaksehir Cam ve Sakura City Hospital, İstanbul, Turkey
| | - Zahide Ekici Tekin
- Department of Pediatric Rheumatology, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Esra Genc
- Department of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazig, Turkey
| | - Fatih Haslak
- Department of Pediatric Rheumatology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
| | - Rana Isguder
- Department of Pediatric Rheumatology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
| | - Aslihan Kara
- Department of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazig, Turkey
| | - Muserref Kasap Cuceoglu
- Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ummusen Kaya Akca
- Department of Pediatric Rheumatology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Hakan Kisaoglu
- Department of Pediatric Rheumatology, Kayseri City Hospital, Kayseri, Turkey
| | | | - Zehra Kızıldag
- Department of Pediatric Rheumatology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
| | - Tuba Kurt
- Department of Pediatric Rheumatology, Bursa City Hospital, Bursa, Turkey
| | - Batuhan Kucukali
- Department of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, 21000, Turkey
| | - Emre Leventoglu
- Department of Pediatric Nephrology, Konya City Hospital, Bursa, Turkey
| | - Hulya Nalcacioglu
- Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
| | - Gulcin Otar Yener
- Department of Pediatric Rheumatology, Eskisehir City Hospital, Eskisehir, Turkey
| | - Semanur Ozdel
- Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey
| | | | - Sumeyra Ozdemir Cicek
- Department of Pediatric Rheumatology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Sule Pektas Leblebiciler
- Department of Pediatric Nephrology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey
| | - Erkin Serdaroglu
- Department of Pediatric Nephrology, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
| | - Hafize Emine Sonmez
- Department of Pediatric Rheumatology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | | | - Serra Surmeli Doven
- Department of Pediatric Nephrology, Faculty of Medicine, Mersin University, Mersin, Türkiye, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
| | - Seher Sener
- Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ayse Tanatar
- Department of Pediatric Rheumatology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Merve Tanidir
- Department of Pediatric Rheumatology, Faculty of Medicine, Gazi University, Ankara, 21000, Turkey
| | - Sema Nur Taskin
- Department of Pediatric Rheumatology, Eskisehir City Hospital, Eskisehir, Turkey
| | - Betul Tiryaki
- Department of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Serife Tuncez
- Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Turkey
| | - Serkan Turkucar
- Department of Pediatric Rheumatology, Faculty of Medicine, Pamukkale University, Denizli, Turkey
| | - Bahriye Uzun Kenan
- Department of Pediatric Nephrology, Ankara Etlik City Hospital, Ankara, Turkey
| | - Nurdan Yildiz
- Department of Pediatric Nephrology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Kenan Yilmaz
- Department of Pediatric Nephrology, Sanlıurfa Training Hospital, Sanlıurfa, Turkey
| | - Yilmaz Tabel
- Department of Pediatric Nephrology, Faculty of Medicine, Inonu University, Malatya, Turkey
| | - Ismail Dursun
- Department of Pediatric Nephrology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Nur Canpolat
- Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University, İstanbul, Turkey
| | - Sevgi Mir
- Department of Pediatric Nephrology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Harun Peru
- Department of Pediatric Nephrology, Faculty of Medicine, Selcuk University, Konya, Turkey
| | - Rezan Topaloglu
- Department of Pediatric Nephrology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Metin Kaya Gurgoze
- Department of Pediatric Nephrology, Faculty of Medicine, Fırat University, Elazig, Turkey
| | - Ayse Balat
- Department of Pediatric Nephrology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Yelda Bilginer
- Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Banu Celikel Acar
- Department of Pediatric Rheumatology, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Betul Sozeri
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey
| | - Erbil Unsal
- Department of Pediatric Rheumatology, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
| | - Ozgür Kasapcopur
- Department of Pediatric Rheumatology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
| | - Sevcan A Bakkaloglu
- Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey
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Jayasinghe M, Rashidi F, Gadelmawla AF, Pitton Rissardo J, Rashidi M, Elendu CC, Fornari Caprara AL, Khalil I, Hmedat KI, Atef M, Moharam H, Prathiraja O. Neurological Manifestations of Systemic Lupus Erythematosus: A Comprehensive Review. Cureus 2025; 17:e79569. [PMID: 40151747 PMCID: PMC11947500 DOI: 10.7759/cureus.79569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2025] [Indexed: 03/29/2025] Open
Abstract
Neurological involvement in systemic lupus erythematosus (SLE) poses significant challenges, impacting patient morbidity, mortality, and quality of life. This narrative review provides an update on the pathogenesis, clinical presentation, diagnosis, and management of neurological SLE. The multifaceted pathophysiology involves immune-mediated and vascular mechanisms such as autoantibodies, neuroinflammation, complement dysregulation, and genetic factors. Neuropsychiatric SLE (NPSLE) manifests in a variety of ways, including cognitive dysfunction, mood disorders, psychosis, cerebrovascular disease, demyelinating syndromes, and neuropathies. Diagnosing neurological SLE is complicated by nonspecific and fluctuating symptoms, requiring comprehensive neurological examination, neuroimaging, autoantibody profiling, and cerebrospinal fluid analysis. Current management strategies include corticosteroids, immunosuppressive agents, and emerging biologics targeting specific immune pathways. Managing neuropsychiatric symptoms, seizures, and neuropathic pain remains a complex aspect of treatment. This review highlights the importance of early recognition and tailored management approaches to improve patient outcomes in neurological SLE.
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Affiliation(s)
| | | | | | | | | | | | | | - Ibrahim Khalil
- Neurological Surgery, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Khalil I Hmedat
- Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria, EGY
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Chiarenza DS, Mancini R, Bigatti C, Caridi G, Consolaro A, Natoli V, Mortari G, Kajana X, Lugani F, Gattorno M, Ghiggeri GM, La Porta E, Gaggero G, Verrina EE, Angeletti A. Case report: Single infusion of combined anti-CD20 and anti-CD38 monoclonal antibodies in pediatric refractory lupus nephritis. Front Immunol 2025; 16:1525892. [PMID: 39935484 PMCID: PMC11810895 DOI: 10.3389/fimmu.2025.1525892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 01/06/2025] [Indexed: 02/13/2025] Open
Abstract
Lupus nephritis (LN), present in 30%-50% of systemic lupus erythematosus (SLE) patients, often necessitates standard immunosuppressive therapy (glucocorticoids, MMF, CYC) as suggested by the European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) and Kidney Disease Improving Global Outcomes (KDIGO) guidelines. However, a subset of subjects remains refractory. Recent findings suggested the efficacy of targeting CD38-long-lived plasma cells in LN and SLE refractory to standard treatment. However, previous experiences were limited to adult patients and described different therapeutical schemes based on daratumumab, with the addition or absence of belimumab. Moreover, the minimal effective dose of daratumumab has yet to be fully defined. In this report, we describe two cases of juvenile-onset refractory LN/SLE successfully managed with a combination of a single infusion of rituximab (targeting CD20 on B cells) and daratumumab (targeting CD38 on long-lived plasma cells), unlike prior regimens requiring prolonged daratumumab infusions. Our approach was safe and effective and may potentially reduce adverse effects and costs, providing a novel therapeutic option for juvenile refractory LN.
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Affiliation(s)
- Decimo Silvio Chiarenza
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Raul Mancini
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Carolina Bigatti
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
- Translational Transplant Research Center and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Gianluca Caridi
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Alessandro Consolaro
- Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy
- Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genova, Italy
| | - Valentina Natoli
- Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy
- Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genova, Italy
| | - Gabriele Mortari
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Xhuliana Kajana
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Francesca Lugani
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Marco Gattorno
- Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy
- Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genova, Italy
| | - Gian Marco Ghiggeri
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Edoardo La Porta
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | | | - Enrico E. Verrina
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Andrea Angeletti
- Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
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Teoh STY, Yap DYH, Yung S, Chan TM. Lupus Nephritis and Chronic Kidney Disease: A Scoping Review. Nephrology (Carlton) 2025; 30:e14427. [PMID: 39776104 DOI: 10.1111/nep.14427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/04/2024] [Accepted: 12/24/2024] [Indexed: 01/11/2025]
Abstract
Prevention of end-stage kidney disease (ESKD) is a major objective in the management of patients with lupus nephritis (LN). Chronic kidney disease (CKD) of variable severity is common in these patients, but recent literature has mostly focused on novel immunosuppressive treatments for acute LN, while the data on CKD is relatively limited. This scoping review aims to summarise available data on the prevalence and risk factors for CKD in patients with LN. PubMed and Web of Science databases were systematically searched on the 1st November 2024 for 'real world' SLE and LN cohorts with longitudinal follow-up which reported the outcome of CKD or CKD progression and its associated risk factors. Fifteen studies were included. The prevalence of CKD ranged from below 10% to almost 50% across diverse LN and SLE cohorts. Major risk factors for CKD or CKD progression included renal impairment at presentation, renal function at 1 year post-treatment, delayed diagnosis, established chronic pathological lesions on kidney biopsy, unsatisfactory treatment response, nephritic flares, hypertension, and persistent proteinuria during follow-up. Many of the identified risk factors are amenable to therapeutic intervention. CKD not only contributes to morbidity and mortality and inferior quality of life, but also influences the choice of therapy and optimal dosing of medications. Attention to immunomodulatory medications for disease control, and non-immune strategies for renoprotection and prevention of CKD complications, are both important in the management of patients with LN to reduce their life-time risk of ESKD.
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Affiliation(s)
- Selene T Y Teoh
- Division of Nephrology, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR
- Division of Nephrology, Department of General Medicine, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Desmond Y H Yap
- Division of Nephrology, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Susan Yung
- Division of Nephrology, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR
| | - Tak Mao Chan
- Division of Nephrology, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong SAR
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van Schaik M, Bredewold OW, Priester M, Michels WM, Rabelink TJ, Rotmans JI, Teng YKO. Long-term renal and cardiovascular risks of tacrolimus in patients with lupus nephritis. Nephrol Dial Transplant 2024; 39:2048-2057. [PMID: 38769592 PMCID: PMC11596090 DOI: 10.1093/ndt/gfae113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Despite continuous advancement, treatment of lupus nephritis (LN) remains challenging. Recent guidelines now include a regimen incorporating tacrolimus as a first-line treatment option. Even though tacrolimus is effective in combination with mycophenolate and corticosteroids, concerns remain regarding long-term use, given its association with increased cardiovascular risks including nephrotoxicity, hypertension, dyslipidemia and hyperglycemia in kidney transplant recipients. However, in LN, long-term evaluations and head-to-head comparisons are lacking and thus the safety profile remains ill-defined. We hypothesized that chronic toxicity also occurs in LN patients. Therefore, this study aimed to assess long-term cardiovascular and renal outcomes of tacrolimus in LN patients. METHODS This observational cohort study examined adult LN patients treated with tacrolimus, assessing renal outcomes, hypertension, diabetes, dyslipidemia, cardiovascular events and the Framingham risk score. The results were compared with a control group of CNI-naïve LN patients. RESULTS Of the 219 LN patients in this study, 43 (19.6%) had tacrolimus exposure. Over a median follow-up of 7.1 years, tacrolimus use was associated with significant kidney function decline (6.8 mL/min/1.73 m2, versus 0.8 in the control group). The incidence of end-stage kidney disease was similar. Cardiovascular event incidence was equally low in both groups. The 10-year risk of coronary heart disease was lower in the tacrolimus group, primarily due to age differences. HbA1c levels were higher in the tacrolimus group (37.4 mmol/mol) than in controls (33.6 mmol/mol), although the incidence of diabetes was similar. There were no differences in the occurrence of hypertension or dyslipidemia. CONCLUSIONS Our study demonstrated that tacrolimus exposure was associated with long-term kidney function loss in LN patients. Although cardiovascular risk factors and events were similar to patients never exposed to tacrolimus, there may be an increased risk of developing diabetes. Therefore, our study supports vigilance towards renal adverse effects in LN patients treated with tacrolimus.
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Affiliation(s)
- Mieke van Schaik
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Obbo W Bredewold
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Merel Priester
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Wieneke M Michels
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ton J Rabelink
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Joris I Rotmans
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Y K Onno Teng
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
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8
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Wenderfer SE, Cooper JC. Do we really need cyclophosphamide for lupus nephritis? Pediatr Nephrol 2024; 39:3193-3200. [PMID: 38607424 DOI: 10.1007/s00467-024-06367-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 03/16/2024] [Accepted: 03/18/2024] [Indexed: 04/13/2024]
Abstract
A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400-1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789-796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753-779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15-29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE.
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Affiliation(s)
- Scott E Wenderfer
- Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada.
- Pediatric Nephrology, BC Children's Hospital, Vancouver, BC, Canada.
| | - Jennifer C Cooper
- Department of Pediatrics, University of Colorado, Denver, CO, USA
- Pediatric Rheumatology, Children's Hospital Colorado, Aurora, CO, USA
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9
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Gerber H, Freercks R. Characteristics and outcomes of biopsy-proven lupus nephritis in the Eastern Cape province of South Africa. Lupus 2024; 33:1289-1298. [PMID: 39241156 PMCID: PMC11437693 DOI: 10.1177/09612033241281042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 07/25/2024] [Accepted: 08/19/2024] [Indexed: 09/08/2024]
Abstract
OBJECTIVE In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome. METHODS A retrospective cohort study of 131 patients with biopsy-proven LN who had a kidney biopsy between 01 January 2012 to 31 December 2021 as identified from the biopsy register. A sub-analysis of 107 patients with proliferative and/or membranous LN was performed. RESULTS Mean age was 31.4 ± 12.7 years with a female predominance of 86.3%. At 6-month follow-up, 69.6% of patients had complete or partial response to treatment. This increased to 70.3% and 72.6% at 18 and 30 months, respectively. Twenty-seven patients were lost to follow-up, while 7 (5.3%) patients progressed to kidney failure (KF). There were 3 (2.3%) deaths. Predictors of poor response were an elevated baseline serum creatinine (OR = 2.53, 95% CI 0.99 - 6.52, p = .054), a decreased eGFR (OR = 2.92, 95% CI 0.94 - 9.09, p = .065) and an elevated blood pressure (OR = 6.06, 95% CI 1.11 - 33.33, p = .038) at the time of biopsy. Infections were the most common adverse event with 50 infections seen in 39 (29.8%) patients. Herpes viral infections were frequently noted (n = 12) accounting for 24.0% of all documented infections. CONCLUSION Response rates were similar in this cohort when compared to other contemporary studies. Predictors of poor response were an elevated baseline serum creatinine, a decreased eGFR and an elevated blood pressure at time of the biopsy. Infections were the most common occurring adverse event, although the mortality rate remained low at 2.3%.
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Affiliation(s)
- Hanri Gerber
- Department of Medicine, Faculty of Health Sciences, Walter Sisulu University, Gqeberha, South Africa
| | - Robert Freercks
- Division of Nephrology and Hypertension, Department of Medicine, Faculty of Health Sciences, Nelson Mandela University, Gqeberha, South Africa
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10
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Hellmich B, Mucke J, Aringer M. [Head-to-head studies on connective tissue diseases and vasculitides]. Z Rheumatol 2024; 83:620-628. [PMID: 39017966 DOI: 10.1007/s00393-024-01537-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2024] [Indexed: 07/18/2024]
Abstract
Head-to-head (H2H) studies enable the direct comparison of several alternative therapeutic approaches and thus provide the evidence-based foundation for the relative position of one treatment as compared to others for a specific indication. These trials constitute an important addition to placebo-controlled clinical trials. Among the controlled clinical trials not performed by the pharmaceutical industry, there are a relevant number of H2H trials for connective tissue diseases (CTDs) and vasculitides, particularly for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article encompasses a review of the H2H trials for CTDs and vasculitides and discusses their relevance for current treatment algorithms. For SLE the H2H trials were predominantly performed for the treatment of lupus nephritis, demonstrating the impact of low-dose cyclophosphamide and mycophenolate as well as azathioprine for maintenance therapy. In recent H2H trials rituximab could be established as induction and maintenance therapy for AAV, which has now been incorporated into current treatment guidelines. Further comparative trials will be necessary in order to select the most effective and safest treatment for every patient, in the sense of personalized medicine.
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Affiliation(s)
- Bernhard Hellmich
- Klinik für Innere Medizin, Rheumatologie, Pneumologie, Nephrologie und Diabetologie, Europäisches Vaskulitis-Referenzzentrum (ERN-RITA), medius KLINIKEN KIRCHHEIM & NÜRTINGEN, Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim unter Teck, Deutschland.
| | - Johanna Mucke
- Klinik für Rheumatologie, Hiller-Forschungszentrum für Rheumatologie, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
| | - Martin Aringer
- Bereich Rheumatologie, Medizinische Klinik und Poliklinik III und Universitätscentrum für Autoimmun- und Rheumatische Erkrankungen (UCARE), Universitätsklinikum und Medizinische Fakultät, TU Dresden, Dresden, Deutschland
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11
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Roveta A, Parodi EL, Brezzi B, Tunesi F, Zanetti V, Merlotti G, Francese A, Maconi AG, Quaglia M. Lupus Nephritis from Pathogenesis to New Therapies: An Update. Int J Mol Sci 2024; 25:8981. [PMID: 39201667 PMCID: PMC11354900 DOI: 10.3390/ijms25168981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/03/2024] [Accepted: 08/15/2024] [Indexed: 09/03/2024] Open
Abstract
Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. This review aims to provide a comprehensive update on progress on several key aspects in this setting: pathogenetic mechanisms of LN, including new insight into the role of autoantibodies, complement, vitamin D deficiency, and interaction between infiltrating immune cells and kidney resident ones; the evolving role of renal biopsy and biomarkers, which may integrate information from renal histology; newly approved drugs such as voclosporin (VOC) and belimumab (BEL), allowing a more articulate strategy for induction therapy, and other promising phase III-immunosuppressive (IS) agents in the pipeline. Several adjunctive treatments aimed at reducing cardiovascular risk and progression of chronic renal damage, such as antiproteinuric agents, represent an important complement to IS therapy. Furthermore, non-pharmacological measures concerning general lifestyle and diet should also be adopted when managing LN. Integrating these therapeutic areas requires an effort towards a holistic and multidisciplinary approach. At the same time, the availability of an increasingly wider armamentarium may translate into improvements in patient's renal outcomes over the next decades.
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Affiliation(s)
- Annalisa Roveta
- Research and Innovation Department (DAIRI), “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (A.R.); (A.F.); (A.G.M.)
| | - Emanuele Luigi Parodi
- Nephrology and Dialysis Unit, “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (E.L.P.); (B.B.)
| | - Brigida Brezzi
- Nephrology and Dialysis Unit, “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (E.L.P.); (B.B.)
| | - Francesca Tunesi
- Nephrology and Dialysis Unit, IRCCS “San Raffaele” Scientific Institute, 20132 Milan, Italy;
| | - Valentina Zanetti
- Department of Internal Medicine, University of Genova, 16126 Genoa, Italy;
| | - Guido Merlotti
- Department of Primary Care, Azienda Socio Sanitaria Territoriale (ASST) of Pavia, 27100 Pavia, Italy;
| | - Alessia Francese
- Research and Innovation Department (DAIRI), “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (A.R.); (A.F.); (A.G.M.)
| | - Antonio G. Maconi
- Research and Innovation Department (DAIRI), “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (A.R.); (A.F.); (A.G.M.)
| | - Marco Quaglia
- Nephrology and Dialysis Unit, “SS Antonio e Biagio e Cesare Arrigo” University Hospital, 15121 Alessandria, Italy; (E.L.P.); (B.B.)
- Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100 Novara, Italy
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12
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Mucke J, Aringer M. [EULAR recommendations 2023 on the treatment of systemic lupus erythematosus -Implications for treatment in Germany]. Z Rheumatol 2024; 83:431-438. [PMID: 39037547 DOI: 10.1007/s00393-024-01544-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 07/23/2024]
Abstract
The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) faced several tasks: the newly approved medications anifrolumab and voclosporin as well as the additional approval of belimumab for lupus nephritis had to be conceptionally fitted into the management of SLE. Novel data on hydroxychloroquine and glucocorticoids, additional results for the treat-to-target goals remission and low disease activity and experience with respect to vaccinations and infections had to be considered. Additionally, EULAR specified a slightly modified structure. The update was further developed with 5 overarching principles and 13 recommendations. An SLE activity score is required for each patient visit. All SLE patients should receive hydroxychloroquine at a target dose of 5 mg/kg body weight. Glucocorticoids should only be used if necessary and reduced to not more than 5 mg prednisone equivalent daily in the long-term or, even better, tapered off. If the target of remission or low disease activity is not reached, methotrexate, azathioprine, mycophenolate and/or belimumab or anifrolumab should be used. For lupus nephritis, Euro-Lupus cyclophosphamide or mycophenolate are options for induction therapy and mycophenolate or azathioprine for maintenance. In the case of severe nephritis, the addition of belimumab or a calcineurin inhibitor (voclosporin or tacrolimus) should be considered. It is important that treatment should be continued for at least 3 years. This review article describes the details of the new recommendations against the background of relevant studies in recent years and classifies them in the clinical context.
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Affiliation(s)
- Johanna Mucke
- Klinik für Rheumatologie, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
- Hiller-Forschungszentrum für Rheumatologie, Medizinische Fakultät, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland
| | - Martin Aringer
- Bereich Rheumatologie, Medizinische Klinik und Poliklinik III und Universitätscentrum für Autoimmun- und Rheumatische Erkrankungen (UCARE), Universitätsklinikum und Medizinische Fakultät TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.
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13
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Houssiau FA. [Treatment of lupus nephritis]. Biol Aujourdhui 2024; 218:25-31. [PMID: 39007774 DOI: 10.1051/jbio/2024006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Indexed: 07/16/2024]
Abstract
Lupus nephritis remains the most frequent severe complication of systemic lupus erythematosus, leading to chronic renal impairment in 20 to 25% of cases. Current treatment is based on the combined use of immunosuppressive treatment and targeted biotherapies to optimize the chances of promptly obtaining and maintaining a complete renal response over the long term. The author discusses these recent advances.
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Affiliation(s)
- Frédéric A Houssiau
- Service de Rhumatologie, Département de Médecine Interne, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Bruxelles, Belgique
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14
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Frangou E, Anders HJ, Bajema IM, Teng YO, Malvar A, Rovin BH, Kronbichler A. Immunosuppression Withdrawal in Patients with Lupus Nephritis: When, How, and for Whom Will It Be Safe? J Am Soc Nephrol 2024; 35:955-958. [PMID: 38985122 PMCID: PMC11230706 DOI: 10.1681/asn.0000000000000365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2024] Open
Affiliation(s)
- Eleni Frangou
- Department of Nephrology, Limassol General Hospital, State Health Services Organization, Limassol, Cyprus
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
| | - Hans-Joachim Anders
- Division of Nephrology, Department of Internal Medicine IV, Hospital of the Ludwig-Maximilians-University, Munich, Germany
| | - Ingeborg M. Bajema
- Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, The Netherlands
| | - Y.K. Onno Teng
- Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic Disease (LuVaCs), Department of Internal Medicine – Section Nephrology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ana Malvar
- Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina
| | - Brad H. Rovin
- Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Andreas Kronbichler
- Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
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15
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Reis-Neto ETD, Seguro LPC, Sato EI, Borba EF, Klumb EM, Costallat LTL, Medeiros MMDC, Bonfá E, Araújo NC, Appenzeller S, Montandon ACDOES, Yuki EFN, Teixeira RCDA, Telles RW, Egypto DCSD, Ribeiro FM, Gasparin AA, Junior ASDA, Neiva CLS, Calderaro DC, Monticielo OA. II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment. Adv Rheumatol 2024; 64:48. [PMID: 38890752 DOI: 10.1186/s42358-024-00386-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 05/25/2024] [Indexed: 06/20/2024] Open
Abstract
OBJECTIVE To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
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Affiliation(s)
- Edgard Torres Dos Reis-Neto
- Division of Rheumatology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/Unifesp), Otonis Street, 863, 2 Floor, Vila Clementino, São Paulo, SP, 04025-002, Brazil.
| | - Luciana Parente Costa Seguro
- Division of Rheumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
| | - Emília Inoue Sato
- Division of Rheumatology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/Unifesp), Otonis Street, 863, 2 Floor, Vila Clementino, São Paulo, SP, 04025-002, Brazil
| | - Eduardo Ferreira Borba
- Division of Rheumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
| | - Evandro Mendes Klumb
- Department of Rheumatology, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Lilian Tereza Lavras Costallat
- Division of Rheumatology, Department of Orthopedics, Rheumatology and Traumatology, Universidade Estadual de Campinas (Unicamp), Campinas, Brazil
| | | | - Eloisa Bonfá
- Division of Rheumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
| | - Nafice Costa Araújo
- Division of Rheumatology, Hospital do Servidor Público Estadual de São Paulo - Instituto de Assistência Médica ao Servidor Público Estadual de São Paulo, São Paulo, Brazil
| | - Simone Appenzeller
- Division of Rheumatology, Department of Orthopedics, Rheumatology and Traumatology, Universidade Estadual de Campinas (Unicamp), Campinas, Brazil
| | | | - Emily Figueiredo Neves Yuki
- Division of Rheumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
| | | | - Rosa Weiss Telles
- Division of Rheumatology, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | | | - Francinne Machado Ribeiro
- Department of Rheumatology, Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Andrese Aline Gasparin
- Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil
| | - Antonio Silaide de Araujo Junior
- Division of Rheumatology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM/Unifesp), Otonis Street, 863, 2 Floor, Vila Clementino, São Paulo, SP, 04025-002, Brazil
| | | | - Debora Cerqueira Calderaro
- Division of Rheumatology, Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
| | - Odirlei Andre Monticielo
- Division of Rheumatology, Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil
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16
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Wang CS, Sadun RE, Zhou W, Miller KR, Pyle L, Ardoin SP, Bacha C, Hause E, Hui-Yuen J, Ling N, Pereira M, Riebschleger M, Rouster-Stevens K, Sarkissian A, Shalen J, Soulsby W, Twilt M, Wu EY, Lewandowski LB, Wenderfer SE, Cooper JC. Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis. Arthritis Rheumatol 2024; 76:469-478. [PMID: 37800549 DOI: 10.1002/art.42725] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 09/07/2023] [Accepted: 09/27/2023] [Indexed: 10/07/2023]
Abstract
OBJECTIVE We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.
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Affiliation(s)
| | | | - Wenru Zhou
- University of Colorado Anschutz Medical Campus, Aurora
| | | | - Laura Pyle
- University of Colorado Anschutz Medical Campus, Aurora
| | | | | | - Emily Hause
- University of Minnesota Masonic Children's Hospital, Minneapolis
| | - Joyce Hui-Yuen
- Cohen Children's Medical Center, New Hyde Park, New York
| | | | - Maria Pereira
- Texas Children's Hospital and Baylor College of Medicine, Houston, Texas
| | | | - Kelly Rouster-Stevens
- Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia
| | | | - Julia Shalen
- Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Marinka Twilt
- Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Laura B Lewandowski
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland
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17
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Elaziz MMA, Gamal SM, Fayed A, Abu-Zaid MH, Ghoniem SA, Teleb DA. High- and low-dose cyclophosphamide in Egyptian lupus nephritis patients: a multicenter retrospective analysis. Z Rheumatol 2024; 83:115-123. [PMID: 37582953 PMCID: PMC10879243 DOI: 10.1007/s00393-023-01386-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/13/2023] [Indexed: 08/17/2023]
Abstract
BACKGROUND Lupus nephritis (LN) is a common serious presentation of systemic lupus erythematosus. Cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are listed as the first-line drugs in induction therapy for LN. OBJECTIVE This study aimed to compare high- and low-dose CYC in a cohort of Egyptian LN patients. PATIENTS AND METHODS The data of 547 patients with class III/IV active LN who received CYC as induction therapy were retrospectively analyzed. Whereas 399 patients received 6‑monthly 0.5-1 g/m2 CYC doses, 148 patients received six biweekly 500 mg CYC doses. Demographic data, laboratory test results, and disease activity index were recorded and compared at presentation and at 6, 12, 18, 24, and 48 months of follow-up. RESULTS After 48 months, the proportion of patients maintaining normal creatinine levels was higher in the group receiving induction therapy with high-dose CYC (67.9%, 60.4%, p = 0.029), and these patients also had higher proteinuria remission at 36 (26.6%, 14.8%, p = 0.014) and 48 months (24.3%, 12.8%, p = 0.006). Comparison of patient outcomes according to both induction and maintenance therapy showed the best results in patients who received high-dose CYC and continued MMF as maintenance therapy. CONCLUSION High- and low-dose CYC are comparable in early phases of treatment. However, after a longer duration of follow-up, high-dose CYC was associated with higher remission rates in the current cohort.
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Affiliation(s)
| | - Sherif M Gamal
- Rheumatology and Rehabilitation Department, Faculty of medicine, Cairo University Hospital, Cairo University, Al Kasr Al Aini, Old Cairo, Cairo Governorate, 4240310, Cairo, Egypt
| | - Ahmed Fayed
- Department of Internal Medicine, Nephrology Unit, Cairo University Hospital, Cairo, Egypt
| | | | - Shada A Ghoniem
- Rheumatology and Rehabilitation Department, Faculty of medicine, Cairo University Hospital, Cairo University, Al Kasr Al Aini, Old Cairo, Cairo Governorate, 4240310, Cairo, Egypt.
| | - Doaa A Teleb
- Rheumatology and Rehabilitation Department, Faculty of medicine, Cairo University Hospital, Cairo University, Al Kasr Al Aini, Old Cairo, Cairo Governorate, 4240310, Cairo, Egypt
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18
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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 2024; 105:S1-S69. [PMID: 38182286 DOI: 10.1016/j.kint.2023.09.002] [Citation(s) in RCA: 78] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 09/07/2023] [Indexed: 01/07/2024]
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19
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Parodis I, Depascale R, Doria A, Anders HJ. When should targeted therapies be used in the treatment of lupus nephritis: Early in the disease course or in refractory patients? Autoimmun Rev 2024; 23:103418. [PMID: 37625673 DOI: 10.1016/j.autrev.2023.103418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 08/21/2023] [Indexed: 08/27/2023]
Abstract
Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5-20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.
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Affiliation(s)
- Ioannis Parodis
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Dermatology, and Rheumatology, Karolinska University Hospital, Stockholm, Sweden; Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Roberto Depascale
- Deparment of Medicine DIMED, Division of Rheumatology, University of Padua, Padua, Italy
| | - Andrea Doria
- Deparment of Medicine DIMED, Division of Rheumatology, University of Padua, Padua, Italy.
| | - Hans-Joachim Anders
- Division of Nephrology, Department of Medicine IV, Hospital of the Ludwig-Maximilians-University, Munich, Germany
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20
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Mejia-Vilet JM, Turner-Stokes T, Houssiau F, Rovin BH. Kidney involvement in systemic lupus erythematosus: From the patient assessment to a tailored treatment. Best Pract Res Clin Rheumatol 2023; 37:101925. [PMID: 38151362 DOI: 10.1016/j.berh.2023.101925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 12/10/2023] [Indexed: 12/29/2023]
Abstract
In the last few years, several studies have provided new evidence for the diagnosis, management, and follow-up of patients with lupus nephritis. Evidence showing dissociation between clinical and histological findings has prompted reevaluation of the role of the kidney biopsy as a tool for diagnosis and follow-up. In therapeutics, four immunosuppressive schemes now have supporting evidence for use as initial therapy. Current challenges include individualized selection of the best immunosuppressive regimen, an unmet need for non-invasive biomarkers of disease activity to inform treatment responses and guide subsequent therapy, holistic patient management in this complex, multisystem disease, and ultimately the development of more targeted therapies directed at specific effector pathways driving glomerular inflammation and damage in order to improve treatment response. In this communication, we review the diagnostic and therapeutic approach to lupus nephritis, as well as evaluation of response to therapy and disease control.
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Affiliation(s)
- Juan M Mejia-Vilet
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Tabitha Turner-Stokes
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, Hammersmith Campus, London, United Kingdom
| | - Frederic Houssiau
- Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Brad H Rovin
- Division of Nephrology, The Ohio State University, Columbus, OH, United States.
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21
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Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. KIDNEY360 2023; 4:1503-1511. [PMID: 37528520 PMCID: PMC10617804 DOI: 10.34067/kid.0000000000000230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 07/25/2023] [Indexed: 08/03/2023]
Abstract
Management of lupus nephritis has evolved considerably over the past years. Here, we provide a comprehensive review of clinical trials that form the basis for the Kidney Disease: Improving Global Outcomes and EULAR/ERA-EDTA updated guidelines and present day trials that will change the landscape of lupus nephritis therapy in years to come. In addition, we highlight the issues related to cost of therapy, resistant disease, and downstream adverse effects of specific therapies.
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Affiliation(s)
- Rupali Avasare
- Nephrology and Hypertension, Oregon Health & Science University School of Medicine, Portland, Oregon
| | - Yelena Drexler
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Dawn J. Caster
- Division of Nephrology and Hypertension, University of Louisville School of Medicine, Louisville, Kentucky
| | - Alla Mitrofanova
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
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22
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Rojas-Rivera JE, García-Carro C, Ávila AI, Espino M, Espinosa M, Fernández-Juárez G, Fulladosa X, Goicoechea M, Macía M, Morales E, Quintana LF, Praga M. Diagnosis and treatment of lupus nephritis: a summary of the Consensus Document of the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Clin Kidney J 2023; 16:1384-1402. [PMID: 37664575 PMCID: PMC10468759 DOI: 10.1093/ckj/sfad055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Indexed: 09/05/2023] Open
Abstract
Lupus nephritis (LN) is the most frequent serious manifestation of patients with systemic lupus erythematosus (SLE). Up to 60% of SLE patients develop LN, which has a significant impact on their quality of life and prognosis. Recent advances have improved the diagnostic approach to LN, and new drugs that block specific pathways and kidney damage progression have been developed. Several randomized and well-powered clinical trials have confirmed the efficacy of these agents in terms of proteinuria remission and preservation of kidney function in the medium and long term, with an acceptable safety profile and good tolerance. The combination of different therapies allows for reduction of the dose and duration of corticosteroids and other potentially toxic therapies and leads to an increase in the number of patients achieving complete remission of the disease. This consensus document carried out by the Spanish Group for the Study of Glomerular Diseases (GLOSEN) provides practical and updated recommendations, based on the best available evidence and clinical expertise of participating nephrologists.
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Affiliation(s)
- Jorge E Rojas-Rivera
- Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
- Departament of Medicine, Universidad Autónoma de Madrid
| | | | | | - Mar Espino
- Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | | | - Xavier Fulladosa
- Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | - Manuel Macía
- Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain
| | - Enrique Morales
- Hospital Universitario 12 de Octubre, Madrid, Spain
- Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain
- Departament of Medicine, Universidad Complutense, Madrid, Spain
| | - Luis F Quintana
- Hospital Clínic de Barcelona, Barcelona, Spain
- Departament of Medicine, Universidad de Barcelona, IDIBAPS, Barcelona, Spain
| | - Manuel Praga
- Instituto de Investigación Hospital Universitario 12 de Octubre, Madrid, Spain
- Departament of Medicine, Universidad Complutense, Madrid, Spain
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23
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Keskinyan VS, Lattanza B, Reid-Adam J. Glomerulonephritis. Pediatr Rev 2023; 44:498-512. [PMID: 37653138 DOI: 10.1542/pir.2021-005259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Glomerulonephritis (GN) encompasses several disorders that cause glomerular inflammation and injury through an interplay of immune-mediated mechanisms, host characteristics, and environmental triggers, such as infections. GN can manifest solely in the kidney or in the setting of a systemic illness, and presentation can range from chronic and relatively asymptomatic hematuria to fulminant renal failure. Classic acute GN is characterized by hematuria, edema, and hypertension, the latter 2 of which are the consequence of sodium and water retention in the setting of renal impairment. Although presenting signs and symptoms and a compatible clinical history can suggest GN, serologic and urinary testing can further refine the differential diagnosis, and renal biopsy can be used for definitive diagnosis. Treatment of GN can include supportive care, renin-angiotensin-aldosterone system blockade, immunomodulatory therapy, and renal transplant. Prognosis is largely dependent on the underlying cause of GN and can vary from a self-limited course to chronic kidney disease. This review focuses on lupus nephritis, IgA nephropathy, IgA vasculitis, and postinfectious GN.
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24
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Beck LH, Ayoub I, Caster D, Choi MJ, Cobb J, Geetha D, Rheault MN, Wadhwani S, Yau T, Whittier WL. KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases. Am J Kidney Dis 2023; 82:121-175. [PMID: 37341661 DOI: 10.1053/j.ajkd.2023.02.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 02/20/2023] [Indexed: 06/22/2023]
Abstract
The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases represents the first update to this set of recommendations since the initial set of KDIGO guideline recommendations was published in 2012. The pace of growth in our molecular understanding of glomerular disease has quickened and a number of newer immunosuppressive and targeted therapies have been introduced since the original set of guideline recommendations, making such an update necessary. Despite these updates, many areas of controversy remain. In addition, further updates since the publication of KDIGO 2021 have occurred which this guideline does not encompass. With this commentary, the KDOQI work group has generated a chapter-by-chapter companion opinion article that provides commentary specific to the implementation of the KDIGO 2021 guideline in the United States.
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Affiliation(s)
- Laurence H Beck
- Division of Nephrology, Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, Massachusetts
| | - Isabelle Ayoub
- Department of Medicine, Division of Nephrology, Wexner Medical, The Ohio State University, Columbus, Ohio
| | - Dawn Caster
- Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky
| | | | - Jason Cobb
- Division of Renal Medicine, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia
| | - Duvuru Geetha
- Division of Nephrology, Johns Hopkins University, Baltimore, Maryland
| | - Michelle N Rheault
- Department of Pediatrics, Division of Pediatric Nephrology, Masonic Children's Hospital, University of Minnesota, Minneapolis, Minnesota
| | - Shikha Wadhwani
- Division of Nephrology and Hypertension, Northwestern University, Chicago, Illinois
| | - Timothy Yau
- Division of Nephrology, Department of Medicine, School of Medicine, Washington University, St. Louis, Missouri
| | - William L Whittier
- Division of Nephrology, Rush University Medical Center, Chicago, Illinois
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25
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Athanassiou P, Athanassiou L. Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus. Life (Basel) 2023; 13:1496. [PMID: 37511872 PMCID: PMC10381582 DOI: 10.3390/life13071496] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 06/18/2023] [Accepted: 06/30/2023] [Indexed: 07/30/2023] Open
Abstract
Systemic lupus erythematosus (SLE), the prototype of systemic autoimmune diseases is characterized by extreme heterogeneity with a variable clinical course. Renal involvement may be observed and affects the outcome. Hydroxychloroquine should be administered to every lupus patient irrespective of organ involvement. Conventional immunosuppressive therapy includes corticosteroids, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine, cyclosporine and tacrolimus. However, despite conventional immunosuppressive treatment, flares occur and broad immunosuppression is accompanied by multiple side effects. Flare occurrence, target organ involvement, side effects of broad immunosuppression and increased knowledge of the pathogenetic mechanisms involved in SLE pathogenesis as well as the availability of biologic agents has led to the application of biologic agents in SLE management. Biologic agents targeting various pathogenetic paths have been applied. B cell targeting agents have been used successfully. Belimumab, a B cell targeting agent, has been approved for the treatment of SLE. Rituximab, an anti-CD20 targeting agent is also used in SLE. Anifrolumab, an interferon I receptor-targeting agent has beneficial effects on SLE. In conclusion, biologic treatment is applied in SLE and should be further evaluated with the aim of a good treatment response and a significant improvement in quality of life.
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Affiliation(s)
| | - Lambros Athanassiou
- Department of Rheumatology, Asclepeion Hospital, Voula, GR16673 Athens, Greece
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26
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Enríquez-Merayo E, Cuadrado MJ. Steroids in Lupus: Enemies or Allies. J Clin Med 2023; 12:jcm12113639. [PMID: 37297834 DOI: 10.3390/jcm12113639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/15/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Glucocorticoids are the gold standard treatment for reducing immune activation and inflammation in a wide range of inflammatory and systemic autoimmune diseases. Glucocorticoids have potent and fast actions that quickly relieve some symptoms and lower mortality in some life-threatening conditions, but they also have side effects that limit the duration of treatment and the dose used. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the involvement of numerous organs and systems and the production of autoantibodies. Most current treatments include the use of corticosteroids and immunosuppressive medications. Glucocorticoids in SLE have been classically used not only to induce remission or treat an acute situation but also as maintenance therapy. During the last decades, new approaches to managing SLE have emerged, but corticosteroids continue to be part of all therapeutic regimes. There is more and more evidence about the side effects related to the use (or abuse) of steroids and their relationship with the accrual damage. In this manuscript, we try to make a critical review of the published literature about the benefit and side effects/damage that can be attributed to the use of glucocorticoids.
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Affiliation(s)
- Eugenia Enríquez-Merayo
- Universitary Hospital 12 de Octubre, 28041 Madrid, Spain
- School of Medicine, Universitary Clínica de Navarra, 28027 Madrid, Spain
| | - Maria J Cuadrado
- School of Medicine, Universitary Clínica de Navarra, 28027 Madrid, Spain
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27
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Zhang D, Sun F, Chen J, Ding H, Wang X, Shen N, Li T, Ye S. Four trajectories of 24-hour urine protein levels in real-world lupus nephritis cohorts. RMD Open 2023; 9:rmdopen-2022-002930. [PMID: 37208030 DOI: 10.1136/rmdopen-2022-002930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 04/20/2023] [Indexed: 05/21/2023] Open
Abstract
OBJECTIVES A 24-hour urine protein (24hUP) is a key measurement in the management of lupus nephritis (LN); however, trajectories of 24hUP in LN is poorly defined. METHODS Two LN cohorts that underwent renal biopsies at Renji Hospital were included. Patients received standard of care in a real-world setting and 24hUP data were collected over time. Trajectory patterns of 24hUP were determined using the latent class mixed modelling (LCMM). Baseline characters were compared among trajectories and multinomial logistic regression was used to determine independent risk factors. Optimal combinations of variables were identified for model construction and user-friendly nomograms were developed. RESULTS The derivation cohort composed of 194 patients with LN with 1479 study visits and a median follow-up of 17.5 (12.2-21.7) months. Four trajectories of 24hUP were identified, that is, Rapid Responders, Good Responders, Suboptimal Responders and Non-Responders, with the KDIGO renal complete remission rates (time to complete remission, months) of 84.2% (4.19), 79.6% (7.94), 40.4% (not applicable) and 9.8% (not applicable), respectively (p<0.001). The 'Rapid Responders' distinguish itself from other trajectories and a nomogram, composed of age, systemic lupus erythematosus duration, albumin and 24hUP yielded C-indices >0.85. Another nomogram to predict 'Good Responders' yielded C-indices of 0.73~0.78, which composed of gender, new-onset LN, glomerulosclerosis and partial remission within 6 months. When applied to the validation cohort with 117 patients and 500 study visits, nomograms effectively sorted out 'Rapid Responders' and 'Good Responders'. CONCLUSION Four trajectories of LN shed some light to guide the management of LN and further clinical trials design.
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Affiliation(s)
- Danting Zhang
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
| | - Fangfang Sun
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
| | - Jie Chen
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
| | - Huihua Ding
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 145 Shandong (M) Rd, Shanghai, 200001, China
| | - Xiaodong Wang
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
| | - Nan Shen
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 145 Shandong (M) Rd, Shanghai, 200001, China
| | - Ting Li
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
| | - Shuang Ye
- Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 2000 Jiangye Rd, Shanghai, 201112, China
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Mok CC, Teng YKO, Saxena R, Tanaka Y. Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol 2023; 19:227-238. [PMID: 36864291 DOI: 10.1038/s41584-023-00925-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2023] [Indexed: 03/04/2023]
Abstract
Despite the continuing development of immunomodulatory agents and supportive care, the prognosis associated with lupus nephritis (LN) has not improved substantially in the past decade, with end-stage kidney disease still developing in 5-30% of patients within 10 years of LN diagnosis. Moreover, inter-ethnic variation in the tolerance of, clinical response to and level of evidence regarding various therapeutic regimens for LN has led to variation in treatment prioritization in different international recommendations. Modalities that better preserve kidney function and reduce the toxicities of concomitant glucocorticoids are unmet needs in the development of therapeutics for LN. In addition to the conventional recommended therapies for LN, there are newly approved treatments as well as investigational drugs in the pipeline, including the newer generation calcineurin inhibitors and biologic agents. In view of the heterogeneity of LN in terms of clinical presentation and prognosis, the choice of therapies depends on a number of clinical considerations. Molecular profiling, gene-signature fingerprints and urine proteomic panels might enhance the accuracy of patient stratification for treatment personalization in the future.
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Affiliation(s)
- Chi Chiu Mok
- Department of Medicine, Tuen Mun Hospital, Hong Kong, China.
| | - Y K Onno Teng
- Center of Expertise for Lupus-, Vasculitis- and Complement-mediated systemic diseases, Department of Internal Medicine, Section of Nephrology, Leiden University Medical Center, Leiden, Netherlands
| | - Ramesh Saxena
- Department of Internal Medicine, Division of Nephrology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Yoshiya Tanaka
- The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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29
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Khandelwal P, Govindarajan S, Bagga A. Management and outcomes in children with lupus nephritis in the developing countries. Pediatr Nephrol 2023; 38:987-1000. [PMID: 36255555 DOI: 10.1007/s00467-022-05769-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 08/14/2022] [Accepted: 09/05/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Lupus nephritis (LN) has variable prevalence, severity, and outcomes across the world. OBJECTIVES This review compares the outcomes of childhood LN in low- and middle-income countries (LMICs) and high-income countries (HICs) and aims to summarize long-term outcomes of pediatric LN from LMICs. DATA SOURCES A systematic literature search, conducted in PubMed, EMBASE, and Cochrane database in the last 30-years from January 1992, published in the English language, identified 113 studies including 52 from lower (n = 1336) and upper MICs (n = 3014). STUDY ELIGIBILITY CRITERIA Cohort studies or randomized controlled trials, of patients ≤ 18 years of age (or where such data can be separately extracted), with > 10 patients with clinically or histologically diagnosed LN and outcomes reported beyond 12 months were included. PARTICIPANTS AND INTERVENTIONS Patients ≤ 18 years of age with clinically or histologically diagnosed LN; effect of an intervention was not measured. STUDY APPRAISAL AND SYNTHESIS METHODS Two authors independently extracted data. We separately analyzed studies from developed countries (high income countries; HIC) and developing countries (LMICs). Middle-income countries were further classified as lower and upper MICs. Meta-analyses of data were performed by calculating a pooled estimate utilizing the random-effects model. Test for heterogeneity was applied using I2 statistics. Publication bias was assessed using funnel plots. RESULTS Kidney remission was similar across MICs and HICs with 1-year pooled complete remission rates of 59% (95% CI 51-67%); one third of patients had kidney flares. The pooled 5-year survival free of stage 5 chronic kidney disease (CKD5) was lower in MICs, especially in lower MICs compared to HICs (83% vs. 93%; P = 0.002). The pooled 5-year patient survival was significantly lower in MICs than HICs (85% vs. 94%; P < 0.001). In patients with class IV LN, the 5-and 10-year respective risk of CKD5 was 14% and 30% in MICs; corresponding risks in HICs were 8% and 17%. Long-term data from developing countries was limited. Sepsis (48.8%), kidney failure (14%), lupus activity (18.1%), and intracranial hemorrhage/infarct (5.4%) were chief causes of death; mortality due to complications of kidney failure was more common in lower MICs (25.6%) than HICs (6.4%). LIMITATIONS The review is limited by heterogenous approach to diagnosis and management that has changed over the period spanning the review. World Bank classification based on income might not correlate with the standards of medical care. The overall quality of evidence is low since included studies were chiefly retrospective and single center. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS Challenges in LMICs include limited access to pediatric nephrology care, dialysis, increased risk of infection-induced mortality, lack of frequent monitoring, and non-compliance due to cost of therapy. Attention to these issues might update the existing data and improve patient follow-up and outcomes. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO 2022 number: CRD42022359002, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359002.
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Affiliation(s)
- Priyanka Khandelwal
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Srinivasavaradan Govindarajan
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Arvind Bagga
- Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
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Mok CC. Combination strategies for lupus nephritis: facts and controversies. Expert Rev Clin Immunol 2023; 19:527-536. [PMID: 36927191 DOI: 10.1080/1744666x.2023.2192927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
INTRODUCTION There is an unmet need to improve the efficacy of therapeutic regimens in lupus nephritis (LN). Cocktail immunosuppressive therapy for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, the potential increase in the risk of serious and opportunistic infections is a concern. Moreover, the timing of combination therapy, adoption of a step-up or step-down approach, and the choice of drugs is still controversial, partly related to the cost-effectiveness issue. AREAS COVERED Evidence of a combination of conventional, newer immunosuppressive, and biologic/targeted agents in LN. EXPERT OPINION Early combination of conventional regimens with anti-B cell activation factor (anti-BAFF) or calcineurin inhibitors (CNIs) enhances the therapeutic effect without increasing serious adverse events in LN. However, combining anti-CD20 and anti-BAFF biologics appears to be less promising from the results of clinical trials. Initial combination strategy may be more cost-effective for patients at risk of treatment failure and renal function deterioration. With the availability of more options, the treat-to-target approach in LN is increasingly feasible and further studies are needed to compare the step-up and step-down approaches in the treatment of LN.
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Affiliation(s)
- Chi Chiu Mok
- Departments of Medicine, Tuen Mun Hospital, Hong Kong, SAR, China
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Adaptation and validation of the Bulgarian version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (L-QoL). Clin Rheumatol 2023:10.1007/s10067-023-06523-w. [PMID: 36913029 DOI: 10.1007/s10067-023-06523-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 03/14/2023]
Abstract
OBJECTIVE Systemic lupus erythematosus (SLE) is a heterogeneous disease with multiple clinical manifestations, which causes a significant deterioration in the quality of life (QoL). The Systemic Lupus Erythematosus Quality of Life Questionnaire (L-QoL) is a lupus-specific measure used to determine the burden of the disease and it applies the need-based model of QoL. Our aim was to produce the first successfully validated foreign language version of the questionnaire. METHODS The development of the Bulgarian version involved three stages: translation, field testing and psychometric evaluation. Translation was conducted by an expert linguist working with a developer of the original L-QoL, followed by interviews with monolingual lay individuals. Face and content validity of the translation were assessed by cognitive debriefing interviews with Bulgarian SLE patients. Finally, the L-QoL was validated by administering the questionnaire to a random sample of SLE patients on two occasions, 2 weeks apart to evaluate its reliability and validity. RESULTS In the validation survey, the new Bulgarian version demonstrated high internal consistency (the Cronbach's alpha coefficient was 0.92), and test-retest reliability (0.97). Additionally, scores on the L-QoL were correlated with those on the SF-36 sections to determine convergent validity and the strongest correlation was observed between L-QoL scores and the social functioning section of the SF-36. Known group validity was established by testing the ability of the Bulgarian L-QoL to distinguish between subgroups of patients from the study pool. CONCLUSIONS The demonstrated excellent psychometric properties ensure that the Bulgarian L-QoL accurately captures the impact of SLE on the quality of life. Key points • The Bulgarian version of the L-QoL is a valid and reliable measure of QoL in lupus patients. • The Bulgarian version of the L-QoL can be used as an outcome measure in research, clinical trials and routine clinical practice.
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Weinmann-Menke J. [Lupus nephritis: from diagnosis to treatment]. INNERE MEDIZIN (HEIDELBERG, GERMANY) 2023; 64:225-233. [PMID: 36763102 DOI: 10.1007/s00108-023-01489-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/27/2023] [Indexed: 02/11/2023]
Abstract
Renal involvement in systemic lupus erythematosus (SLE), so-called lupus nephritis (LN), is one of the most frequent organ manifestations with an incidence of approximately 40-60%. It is not uncommon for renal involvement to be the initial manifestation of SLE or to occur in the first 5-10 years after diagnosis of SLE. Urinalysis is useful in screening for the presence of LN, demonstrating proteinuria or active sediment with acanthocytes. Histologic confirmation of LN, and thus the LN class present, is currently the gold standard for confirming the diagnosis. In addition, knowledge of the LN class is a relevant component of adequate treatment planning in SLE patients with LN. In particular, early diagnosis and rapid response to therapy are of prognostic importance for the preservation of renal function as well as morbidity and mortality of the mostly young patients at the time of initial diagnosis. Thus, the focus of therapy is to achieve complete remission, as well as to avoid active disease phases. Due to a complex pathogenesis and at the same time a very heterogeneous clinical presentation, with six different histological classes of LN, there are different therapeutic targets. This in turn results in a significant expansion of the study landscape in the field of LN with an increasing understanding of the signaling pathways and influencing factors, and fortunately in a growing armamentarium of available targeted therapy options. Simultaneously, new insights into drug therapy to inhibit progression of chronic renal disease are opening up supportive therapy options that can further improve preservation of renal function.
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Affiliation(s)
- Julia Weinmann-Menke
- I. Medizinische Klinik und Poliklinik, Schwerpunkt Nephrologie und Nierentransplantation, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland.
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Faustini F, Idborg H, Fuzzi E, Larsson A, Lie WR, Pötzsch S, Okitsu SL, Svenungsson E, Gunnarsson I. Urine Galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus. Lupus 2023; 32:252-262. [PMID: 36508734 PMCID: PMC9939930 DOI: 10.1177/09612033221145534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. OBJECTIVE To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. PATIENTS AND METHODS Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. RESULTS Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. CONCLUSION Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.
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Affiliation(s)
- Francesca Faustini
- Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden
| | - Helena Idborg
- Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden
| | - Enrico Fuzzi
- Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden.,Division of Rheumatology, Department of Medicine DIMED, Padua University Hospital, Padua, Italy
| | - Anders Larsson
- Department of Medical Sciences/Clinical Chemistry, 8097Uppsala University, Uppsala, Sweden
| | | | | | - Shinji L Okitsu
- 189697EMD Serono Research and Development Institute, Billerica, MA, USA
| | - Elisabet Svenungsson
- Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden
| | - Iva Gunnarsson
- Division of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, 27106Karolinska Institute, Stockholm, Sweden
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Rojas-Rivera JE, García-Carro C, Ávila AI, Espino M, Espinosa M, Fernández-Juárez G, Fulladosa X, Goicoechea M, Macía M, Morales E, Porras LFQ, Praga M. Consensus document of the Spanish Group for the Study of the Glomerular Diseases (GLOSEN) for the diagnosis and treatment of lupus nephritis. Nefrologia 2023; 43:6-47. [PMID: 37211521 DOI: 10.1016/j.nefroe.2023.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 10/17/2022] [Indexed: 05/23/2023] Open
Abstract
A significant number of patients with systemic lupus erythematosus (between 20% and 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients.
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Affiliation(s)
- Jorge E Rojas-Rivera
- Hospital Universitario Fundación Jiménez Díaz, Servicio de Nefrología e Hipertensión, Madrid, Spain; Department of Medicine, Universidad Autónoma de Madrid, Servicio de Nefrología, Madrid, Spain.
| | - Clara García-Carro
- Hospital Universitario Clínico San Carlos, Servicio de Nefrología. Madrid, Spain.
| | - Ana I Ávila
- Hospital Dr. Peset, Servicio de Nefrología, Valencia, Spain
| | - Mar Espino
- Hospital Universitario 12 de Octubre, Servicio de Nefrología, Madrid, Spain
| | - Mario Espinosa
- Hospital Universitario Reina Sofía, Servicio de Nefrología, Cordoba, Spain
| | | | - Xavier Fulladosa
- Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Servicio de Nefrología, Barcelona, Spain
| | - Marian Goicoechea
- Hospital Universitario Gregorio Marañón, Servicio de Nefrología, Madrid, Spain
| | - Manuel Macía
- Hospital Universitario Nuestra Señora de la Candelaria, Servicio de Nefrología, Tenerife, Spain
| | - Enrique Morales
- Hospital Universitario 12 de Octubre, Servicio de Nefrología, Madrid, Spain; Instituto de Investigación Hospital Universitario 12 de Octubre, Servicio de Nefrología, Madrid, Spain; Departamento de Medicina, Universidad Complutense, Servicio de Nefrología, Madrid, Spain
| | - Luis F Quintana Porras
- Hospital Clínic de Barcelona, Servicio de Nefrología, Barcelona, Spain; Departamento de Medicina, Universidad de Barcelona, IDIBAPS, Servicio de Nefrología, Barcelona, Spain
| | - Manuel Praga
- Instituto de Investigación Hospital Universitario 12 de Octubre, Servicio de Nefrología, Madrid, Spain; Departamento de Medicina, Universidad Complutense, Servicio de Nefrología, Madrid, Spain
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Protective role of T regulatory (Treg) cells in systemic lupus erythematosus patients with nephritis. THE EGYPTIAN RHEUMATOLOGIST 2023. [DOI: 10.1016/j.ejr.2022.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Cao TT, Chen L, Zhen XF, Zhao GJ, Zhang HF, Hu Y. Dan Bai Xiao Formula combined with glucocorticoids and cyclophosphamide for pediatric lupus nephritis: A pilot prospective study. World J Clin Cases 2022; 10:11391-11402. [PMID: 36387787 PMCID: PMC9649537 DOI: 10.12998/wjcc.v10.i31.11391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/01/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Patients with lupus nephritis (LN) typically undergo long-term treatment with glucocorticoids (GCs) and immunosuppressants. There is a growing demand for optimal therapy with better remission results and fewer side effects. Sustained traditional Chinese medicine (TCM) might be quite valuable for multitarget therapy, reducing the total dosage of GCs and minimizing the side effects of immunosuppressants.
AIM To evaluate whether Dan Bai Xiao Formula (DBXF) can reduce the exposure to GCs and cyclophosphamide (CYC) and to assess the efficacy and safety of DBXF for the resolution of proteinuria and hematuria in children with LN.
METHODS A 24-wk pilot study was conducted at Beijing Children’s Hospital. Children with active LN were divided into either a TCM group or a control group. Children in the TCM group received DBXF combined with GCs and CYC, and the ones in the control group received GCs and CYC every 4 wk for 24 wk. The primary endpoints of this trial were urinary protein excretion of < 150 mg/d and normal serum albumin concentration and renal function.
RESULTS The trial included 78 children, of whom 38 received GCs and CYC treatment (control group) and the remaining 40 received DBXF combined with GCs and CYC treatment (TCM group). At week 24, the TCM group showed a better rate of complete remission (42.5%); however, there was no significant difference compared with the control group (31.5%, P > 0.05). The urine red blood cell count and urine protein level were significantly lower in the TCM group than in the control group at weeks 4, 12, and 24 (P < 0.05). Furthermore, patients in the TCM group had a lower proportion of methylprednisolone pulses than those in the control group (1.30 ± 1.41 vs 3.05 ± 2.02, P < 0.0001). The ending GC dose was significantly lower in the TCM group than in the control group (P < 0.001). Moreover, more hepatic function damage, gastrointestinal adverse effects, and hypertension were observed in the control group than in the TCM group (P < 0.05).
CONCLUSION The findings suggest that DBXF treatment is effective and safe as a supplementary therapy for LN and is superior to routine GC and CYC therapy. DBXF containing combination treatment possibly results in a faster resolution of proteinuria and hematuria, smoother GC reduction, fewer methylprednisolone pulses, and fewer adverse events.
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Affiliation(s)
- Tong-Tong Cao
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Li Chen
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Xiao-Fang Zhen
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Gao-Jie Zhao
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Hui-Fang Zhang
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
| | - Yan Hu
- Department of Traditional Chinese Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
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Diagnostic test accuracy of novel biomarkers for lupus nephritis-An overview of systematic reviews. PLoS One 2022; 17:e0275016. [PMID: 36215243 PMCID: PMC9550089 DOI: 10.1371/journal.pone.0275016] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 09/08/2022] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area. METHODS The research question is "What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?". We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool). RESULTS Ten SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias. CONCLUSIONS There are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future. REGISTRATION This project is registered on the International Prospective Registry of Systematic Reviews (PROSPERO) database (CRD42020196693).
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Documento de consenso del Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) para el diagnóstico y tratamiento de la nefritis lúpica. Nefrologia 2022. [DOI: 10.1016/j.nefro.2022.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Sada K, Kurita N, Noma H, Matsuki T, Quasny H, Levy RA, Jones-Leone AR, Gairy K, Yajima N. MOONLIGHT study: the design of a comparative study of the effectiveness of belimumab in patients with a history of lupus nephritis from the post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide reGistry (LUNA) coHorT. Lupus Sci Med 2022; 9:9/1/e000746. [PMID: 37017254 PMCID: PMC9438087 DOI: 10.1136/lupus-2022-000746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/23/2022] [Indexed: 11/18/2022]
Abstract
Introduction Lupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase. Methods and analysis This multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab’s effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations. Ethics and dissemination This study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings.
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Affiliation(s)
- Kenei Sada
- Department of Clinical Epidemiology, Kochi Medical School, Kochi University, Kochi, Japan
| | - Noriaki Kurita
- Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, Fukushima, Japan
- Department of Clinical Epidemiology, Graduate School of Medicine, Fukushima Medical University, Fukushima, Japan
| | - Hisashi Noma
- Department of Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
| | - Taizo Matsuki
- Value Evidence and Outcomes Division, GSK K.K, Tokyo, Japan
| | - Holly Quasny
- Clinical Sciences, GSK, Research Triangle Park, North Carolina, USA
| | - Roger A Levy
- Global Medical Affairs, GSK, Collegeville, Pennsylvania, USA
| | | | - Kerry Gairy
- Value Evidence and Outcomes Division, GSK, Brentford, UK
| | - Nobuyuki Yajima
- Division of Rheumatology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
- Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan
- Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan
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Yu C, Li P, Dang X, Zhang X, Mao Y, Chen X. Lupus nephritis: new progress in diagnosis and treatment. J Autoimmun 2022; 132:102871. [PMID: 35999111 DOI: 10.1016/j.jaut.2022.102871] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 07/12/2022] [Indexed: 02/07/2023]
Abstract
Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease that affects many organs, including the kidney. Lupus nephritis (LN) is a common manifestation characterized by heterogeneous clinical and histopathological findings, and often associates with poor prognosis. The diagnosis and treatment of LN is challenging, depending largely on renal biopsy, and there is no reliable non-invasive LN biomarker. Up to now, the complete remission rate of LN is only 20%∼30% after receiving six months of standard treatment, which is far from satisfactory. Moreover, adverse reactions to immunosuppressants, especially glucocorticoids, further compromise the prognosis of LN. Biological reagents targetting autoimmune responses and inflammatory pathways, bring hope to the treatment of intractable lupus. The European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) and KDIGO (Kidney Disease: Improving Global Outcomes) have been working on and launched the recommendations for the management of LN. In this review, we update our knowledge in the pathogenesis, diagnosis, and management of LN and prospect for the future potential targets in the management of LN.
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Affiliation(s)
- Chen Yu
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Ping Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Xin Dang
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xuan Zhang
- Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yonghui Mao
- Department of Nephrology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
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Suzon B, Louis-Sidney F, Aglaé C, Henry K, Bagoée C, Wolff S, Moinet F, Emal-Aglaé V, Polomat K, DeBandt M, Deligny C, Couturier A. Good Long-Term Prognosis of Lupus Nephritis in the High-Income Afro-Caribbean Population of Martinique with Free Access to Healthcare. J Clin Med 2022; 11:jcm11164860. [PMID: 36013099 PMCID: PMC9410092 DOI: 10.3390/jcm11164860] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/12/2022] [Accepted: 05/18/2022] [Indexed: 11/16/2022] Open
Abstract
Lupus nephritis (LN) has been described as having worse survival and renal outcomes in African-descent patients than Caucasians. We aimed to provide long-term population-based data in an Afro-descendant cohort of LN with high income and easy and free access to specialized healthcare. Study design: We performed a retrospective population-based analysis using data from 2002–2015 of 1140 renal biopsies at the University Hospital of Martinique (French West Indies). All systemic lupus erythematosus patients with a diagnosis of LN followed for at least 12 months in Martinique or who died during this period were included. Results: A total of 89 patients were included, of whom 68 (76.4%) had proliferative (class III or IV), 17 (19.1%) had membranous (class V), and 4 (4.5%) had class I or II lupus nephritis according to the ISN/RPS classification. At a mean follow-up of 118.3 months, 51.7% of patients were still in remission. The rates of end-stage renal disease were 13.5%, 19.1%, and 21.3% at 10, 15, and 20 years of follow-up, respectively, and mortality rates were 4.5%, 5.6%, and 7.9% at 10, 15, and 20 years of follow-up, respectively. Conclusions: The good survival of our Afro-descendant LN patients, similar to that observed in Caucasians, shades the burden of ethnicity but rather emphasizes and reinforces the importance of optimizing all modifiable factors associated with poor outcome, especially socioeconomics.
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Affiliation(s)
- Benoit Suzon
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
- Correspondence:
| | - Fabienne Louis-Sidney
- Department of Rheumatology, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Cédric Aglaé
- Department of Nephrology, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Kim Henry
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Cécile Bagoée
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Sophie Wolff
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Florence Moinet
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Violaine Emal-Aglaé
- Department of Nephrology, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Katlyne Polomat
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Michel DeBandt
- Department of Rheumatology, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Christophe Deligny
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
| | - Aymeric Couturier
- Department of Internal Medicine, Martinique University Hospital, CEDEX CS, 90632 Fort-de-France, Martinique, France
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Moroni G, Porata G, Raffiotta F, Frontini G, Calatroni M, Reggiani F, Banfi G, Ponticelli C. Predictors of increase in chronicity index and of kidney function impairment at repeat biopsy in lupus nephritis. Lupus Sci Med 2022; 9:9/1/e000721. [PMID: 35973744 PMCID: PMC9386217 DOI: 10.1136/lupus-2022-000721] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/30/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Based on available data, the histological predictors of long-term outcome of lupus nephritis (LN) are not clearly defined. Aims of this retrospective study were: (i) to evaluate the change of chronicity index from the first to second kidney biopsy and to find the predictors of chronicity index increase and (ii) to detect the clinical/histological features at first and at second kidney biopsy associated with long-term kidney function impairment. METHODS Among 203 biopsy proven LN subjects, 61 repeated kidney biopsy 49 months after the first biopsy. The reasons for repeated biopsy were: nephritic flares in 25 (41%), proteinuric flares in 21 (36%) of patients and protocol biopsy in 14 (23%) of cases. RESULTS During 23-year follow-up, 25 patients presented a decrease in glomerular filtration rate (eGFR) ≥30%. At repeat biopsy, chronicity index increased in 44 participants (72%) and did not increase in 17 (28%). Nephritic syndrome and serum creatinine >1.6 mg/dL at presentation correlated with chronicity index increase (p=0.031, 0.027, respectively), cyclophosphamide therapy tended to protect against chronicity index increase (p=0.059). Kidney flares occurred in 53.6% of patients with vs 23.5% of those without chronicity index increase (p=0.035). Chronicity index increases of 3.5 points in patients with kidney flares vs 2 in those without flares (p=0.001). At second, but not at first kidney biopsy, two different models predicted eGFR decrease at multivariate analysis. The first included activity index >3 (OR: 3.230; p=0.013) and chronicity index >4 (OR: 2.905; p=0.010), and the second model included moderate/severe cellular/fibrocellular crescents (OR: 4.207; p=0.010) and interstitial fibrosis (OR: 2.525; p=0.025). CONCLUSION At second biopsy, chronicity index increased in 3/4 of participants. Its increase was predicted by kidney dysfunction at presentation and occurrence of LN flares. Kidney function impairment was predicted by both activity and chronicity index and by some of their components at repeated biopsy, but not at first biopsy.
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Affiliation(s)
- Gabriella Moroni
- Department of Biomedical Sciences, Humanitas University, Milan, Italy .,Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Giulia Porata
- U.O. Nefrologia e Dialisi, ASST Santi Paolo e Carlo, Milano, Italy
| | | | - Giulia Frontini
- Nefrologia, Dialisi e Trapianto di Rene, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marta Calatroni
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Francesco Reggiani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,Nephrology and Dialysis Division, IRCCS Humanitas Research Hospital, Rozzano, Italy
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Recommendations for Systemic Lupus Erythematosus. Rheum Dis Clin North Am 2022; 48:617-636. [DOI: 10.1016/j.rdc.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Abstract
The nitrogen mustards are powerful cytotoxic and lymphoablative agents and have been used for more than 60 years. They are employed in the treatment of cancers, sarcomas, and hematologic malignancies. Cyclophosphamide, the most versatile of the nitrogen mustards, also has a place in stem cell transplantation and the therapy of autoimmune diseases. Adverse effects caused by the nitrogen mustards on the central nervous system, kidney, heart, bladder, and gonads remain important issues. Advances in analytical techniques have facilitated the investigation of the pharmacokinetics of the nitrogen mustards, especially the oxazaphosphorines, which are prodrugs requiring metabolic activation. Enzymes involved in the metabolism of cyclophosphamide and ifosfamide are very polymorphic, but a greater understanding of the pharmacogenomic influences on their activity has not yet translated into a personalized medicine approach. In addition to damaging DNA, the nitrogen mustards can act through other mechanisms, such as antiangiogenesis and immunomodulation. The immunomodulatory properties of cyclophosphamide are an area of current exploration. In particular, cyclophosphamide decreases the number and activity of regulatory T cells, and the interaction between cyclophosphamide and the intestinal microbiome is now recognized as an important factor. New derivatives of the nitrogen mustards continue to be assessed. Oxazaphosphorine analogs have been synthesized in attempts to both improve efficacy and reduce toxicity, with varying degrees of success. Combinations of the nitrogen mustards with monoclonal antibodies and small-molecule targeted agents are being evaluated. SIGNIFICANCE STATEMENT: The nitrogen mustards are important, well-established therapeutic agents that are used to treat a variety of diseases. Their role is continuing to evolve.
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Affiliation(s)
- Martin S Highley
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Bart Landuyt
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Hans Prenen
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Peter G Harper
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Ernst A De Bruijn
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
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Lledó-Ibáñez GM, Xipell M, Ferreira M, Solé M, Garcia-Herrera A, Cervera R, Quintana LF, Espinosa G. Kidney biopsy in lupus nephritis after achieving clinical renal remission: paving the way for renal outcome assessment. Clin Kidney J 2022; 15:2081-2088. [PMID: 36325009 PMCID: PMC9613421 DOI: 10.1093/ckj/sfac150] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Indexed: 12/03/2022] Open
Abstract
The role of repeat kidney biopsy in lupus nephritis (LN) with renal remission is unclear. The aim of this study was to assess this role in a real-life scenario. This retrospective, single-centre study included 56 patients with LN diagnosed from 1998 to 2019, with an initial kidney biopsy (KB1) at the onset of LN and a second kidney biopsy (KB2) after achieving renal remission. A total of 51 (91.1%) patients were women with a median age of 29.9 years [interquartile range (IQR) 23.4–40.6] at the time of LN diagnosis. KB2s were performed after 41.1 months (IQR 30.1–52.5) of KB1. At the time of KB2, complete renal response was achieved in 51 (91.1%) patients. The median activity index decreased from a baseline value of 6.5 (IQR 2.8–11) to 0 (IQR 0–2) (P < .001). The chronicity index worsened from 1 (IQR 0–2) to 2 (IQR 1–3) (P = .01). In patients with proliferative/mixed forms at KB2, the chronicity index median value increased to 3 (IQR 1.5–4), as well as interstitial fibrosis and tubular atrophy \documentclass[12pt]{minimal}
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}{}$\ge $\end{document}25%, from 5.4% to 13.5%. Persistent histological active LN (activity index ≥2) was present in 11 (19.6%) KB2s. There were no differences when comparing immunological parameters between both groups (activity index ≥2 versus <2) at KB2, nor in the percentage of patients who presented renal flare. Immunosuppressive treatment was withdrawn in 35 (62.5%) patients and maintained/switched in 21 (37.5%). Afterward, new renal flare occurred in 9 patients per group (25.7% and 43%, respectively), after a median time of 39 months (IQR 6.5–55) and 7 months (IQR 6–30), respectively. There was no difference in the number of patients who developed chronic kidney disease [n = 14 (25%)] according to the treatment. In conclusion, KB2 provides valuable information to guide immunosuppressive maintenance therapy.
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Affiliation(s)
- Gema Maria Lledó-Ibáñez
- Department of Autoimmune Diseases-Reference Centre (CSUR) for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona , Barcelona, Catalonia , Spain
| | - Marc Xipell
- Department of Nephrology and Renal Transplantation – Reference Center (CSUR) for Glomerular Complex Diseases of the Spanish Health System, Hospital Clínic, Department of Medicine, University of Barcelona, IDIBAPS , Barcelona, Catalonia , Spain
| | - Manuel Ferreira
- Department of Autoimmune Diseases-Reference Centre (CSUR) for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona , Barcelona, Catalonia , Spain
| | - Manel Solé
- Department of Pathology – Reference Center (CSUR) for Glomerular Complex Diseases of the Spanish Health System, Hospital Clínic, Department of Medicine, University of Barcelona, IDIBAPS , Barcelona, Catalonia , Spain
| | - Adriana Garcia-Herrera
- Department of Pathology – Reference Center (CSUR) for Glomerular Complex Diseases of the Spanish Health System, Hospital Clínic, Department of Medicine, University of Barcelona, IDIBAPS , Barcelona, Catalonia , Spain
| | - Ricard Cervera
- Department of Autoimmune Diseases-Reference Centre (CSUR) for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona , Barcelona, Catalonia , Spain
| | - Luis F Quintana
- Department of Nephrology and Renal Transplantation – Reference Center (CSUR) for Glomerular Complex Diseases of the Spanish Health System, Hospital Clínic, Department of Medicine, University of Barcelona, IDIBAPS , Barcelona, Catalonia , Spain
| | - Gerard Espinosa
- Department of Autoimmune Diseases-Reference Centre (CSUR) for Systemic Autoimmune Diseases of the Spanish Health System, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona , Barcelona, Catalonia , Spain
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Yadav S, Balakrishnan C, Kothari J. Long-term outcome and predictors of long-term outcome in patients with lupus nephritis managed at a tertiary hospital in Mumbai. Lupus 2022; 31:1191-1201. [PMID: 35658736 DOI: 10.1177/09612033221106607] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AIM Study the long-term outcome of the patients with LN and identify the baseline factors that can predict the long-term outcome of these patients. METHODS All biopsy-proven LN patients who attended our regular 'lupus nephritis' clinic from 2013 to 2021 were studied. Data of these patients were collected from the hospital patient records. Standard therapy was given as per the KDIGO guidelines, and the renal response was evaluated according to KDIGO outcome criteria. Cox' regression analysis was used to determine predictors of chronic kidney disease (persistent doubling of serum creatinine with creatinine ≥1.5 mg%). Kaplan-Meier analysis was used for renal survival. RESULTS Eighty patients with at least 1 year of follow-up were included. Median age of onset was 24 years (IQR18-35). Median follow up was 6.5 years (IQR 3-10). World Health Organisation renal biopsy profile was Class I 1(1.2 %), Class II 6(7.5 %), Class III 9(11.2 %), Class IV 36(45 %), Class V 18(22.5 %) and Mixed Class IV + V 10 (12%). Complete remission was achieved in 63.75%, 70 % and 66.6% patients at 1, 2 and 5 years, respectively. Survival with normal renal function was 88.5 %, 85.8% and 60 % at 5, 10 and 15 years, respectively. Risk factors for poor outcome on univariate analysis were presence of Raynaud's phenomena-hazard ratio(HR) 7.78 (CI 1.944-31.207; p < .004), baseline hypertension-HR 5.356 (CI 1.479-19.403; p < .011), tubulointerstitial involvement-HR 1.076 (CI 1.032-1.222; p < .001), time to complete response-HR 1.036 (CI 1.036-1.067; p < .02 ), serum creatinine at 6 months HR 10.51 (CI 2.19-50.39; p < .003), failure to achieve complete response at 2 years HR 6.271 (CI 1.567-25.092; p < .009) and the number of nephritic flares HR 1.868(CI 1.103-3.164 ; p < .02). Renal relapses were quite common, with 1.8 flares per 10 patient-years of follow up. Infection was the most common cause of death, with bacterial lower respiratory infections and pulmonary tuberculosis being the most common. CONCLUSIONS Apart from conventional risk factors, other predictive factors like the presence of Raynaud's phenomenon, tubulointerstitial fibrosis and tubular atrophy on kidney biopsy, and initial response to induction therapy by 6 months have a significant impact on the long-term outcome in patients with LN.
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Affiliation(s)
- Sandeep Yadav
- Department of Rheumatology, 29537P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - C Balakrishnan
- Department of Rheumatology, 29537P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - Jatin Kothari
- Department of Nephrology, 29537PD Hinduja National Hospital and Medical Research Centre, Khar Mumbai, India.,Apex Kidney Foundation, Mumbai, India.,Apex Kidney Care - Dialysis Networks, Mumbai, India.,Nanavati Max Hospital, Mumbai, India
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Cannon LA, Wenderfer SE, Lewandowski LB, Cooper JC, Goilav B, Knight AM, Hersh AO, Ardoin SP, Sadun RE. Use of EuroLupus Cyclophosphamide Dosing for the Treatment of Lupus Nephritis in Childhood-onset Systemic Lupus Erythematosus in North America. J Rheumatol 2022; 49:607-614. [PMID: 35169053 PMCID: PMC10464387 DOI: 10.3899/jrheum.210428] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Childhood-onset systemic lupus erythematosus (cSLE) has higher rates of lupus nephritis (LN) than adult-onset SLE, often requiring intensive immunosuppression. This study examined North American practices and preferences for the low-dose EuroLupus cyclophosphamide (CYC) protocol, as compared to the high-dose National Institutes of Health (NIH) CYC protocol, to treat LN in cSLE. METHODS A 35-item Web-based survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) and Pediatric Nephrology Research Consortium (PNRC) providers. The survey assessed participant demographics, CYC prescribing practices, perceptions of EuroLupus protocol, and LN vignette treatment decisions; 1 vignette was taken from a 2009 CARRA survey and responses were compared. Multivariable logistic regression analyzed provider factors associated with use of low- vs high-dose CYC. RESULTS Responses were provided by 185/421 (44%) pediatric rheumatologists (CARRA) and 40/354 (11%) pediatric nephrologists (PNRC). Among respondents who prescribed CYC for pediatric LN over the past year (n = 135), half reported using EuroLupus. When presented with the same vignette about an adolescent with class IV LN, 32% of pediatric rheumatologists chose EuroLupus dosing in 2020, vs 6% in 2009. Provider factors associated with choosing the low-dose regimen were familiarity with the protocol (OR 4.2, P = 0.006) and greater perceived benefit (OR 1.6, P < 0.0001). Pediatric nephrologists had similar responses to the pediatric rheumatology providers. Overall, 78% of respondents perceived EuroLupus protocol efficacy to be equivalent to the high-dose protocol in cSLE LN. CONCLUSION Pediatric specialists are currently more likely to use low-dose CYC to treat cSLE LN than they were a decade ago. Nevertheless, familiarity with EuroLupus dosing remains low.
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Affiliation(s)
- Laura A Cannon
- L.A. Cannon, MD, Division of Pediatric Rheumatology, Department of Pediatrics, Duke University, Durham, and Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;
| | - Scott E Wenderfer
- S.E. Wenderfer, MD, Department of Pediatrics, Baylor College of Medicine; Renal Section, Texas Children's Hospital, Houston, Texas, USA
| | - Laura B Lewandowski
- L.B. Lewandowski, MD, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Jennifer C Cooper
- J.C. Cooper, MD, Division of Pediatric Rheumatology, Department of Pediatrics, University of Colorado, Denver, Colorado, USA
| | - Beatrice Goilav
- B. Goilav, MD, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Andrea M Knight
- A.M. Knight, MD, Division of Pediatric Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Aimee O Hersh
- A.O. Hersh, MD, Division of Pediatric Rheumatology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
| | - Stacy P Ardoin
- S.P. Ardoin, MD, Division of Pediatric Rheumatology, Department of Pediatrics, and Division of Rheumatology, Department of Medicine, The Ohio State University, Columbus, Ohio, USA
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Portalatin GM, Gebreselassie SK, Bobart SA. Lupus nephritis - An update on disparities affecting african americans. J Natl Med Assoc 2022; 114:S34-S42. [PMID: 35595581 DOI: 10.1016/j.jnma.2022.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Lupus Nephritis is a complex clinical manifestation of systemic lupus erythematosus (SLE) associated with significant morbidity and mortality. It disproportionately affects minorities, especially African Americans (AA) with higher rates of progression to end stage kidney disease. Several factors are implicated including genetic predisposition to both SLE and chronic kidney disease, social determinants of health such as income inequality, education disparities, social isolation/lack of support, health care access and affordability. Clinically, AA may have higher auto-antibody titers, including several antibodies occurring simultaneously. AA are more prone to severe disease such as Class III and IV lupus nephritis. Fortunately, clinical trials have shown a favorable benefit/response among African Americans to mycophenolate mofetil. However, newer and alternative agents such as Rituximab, Belimumab and Voclosporin are widely unaffordable, and AA remain underrepresented in these clinical trials. The current state of disparities affecting LN patients of AA ancestry is a call for better access to healthcare and social support systems, greater inclusion/representation in clinical trials, and making new and alternative regimens more affordable and cost effective.
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Affiliation(s)
- Gilda M Portalatin
- Department of Internal Medicine, Cleveland Clinic Florida, Weston, FL, United States
| | | | - Shane A Bobart
- Department of Kidney Medicine, Cleveland Clinic Florida, Weston, FL, United States.
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49
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He W, Xie P, Li W, Yao F, Liu Y, Liang L, Liu D. Impaired left ventricular systolic synchrony in patients with lupus Nephritis: A speckle tracking echocardiography study. Lupus 2022; 31:1084-1093. [PMID: 35575173 DOI: 10.1177/09612033221102713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES We aimed to explore the value of two-dimensional speckle tracking echocardiography measurements of the global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) in the assessment of early stage left ventricular systolic dysfunction and heterogeneity of myocardial contraction in patients with lupus nephritis (LN). METHODS Patients with LN and extra-renal systemic lupus erythematosus (SLE) and healthy participants in the control group underwent echocardiography for the traditional measurement of the left ventricular systolic and diastolic function and speckle tracking measurements of the GLS and LVMD. GLS was defined as the average value of the peak strain during systole of the left ventricular 17 segments, and LVMD was defined as the standard deviation. The demographic characteristics including age, sex, and body mass index (BMI) of all the participants were collected. The clinical and laboratory characteristics of the patients with LN were collected. RESULTS We included 41 healthy control, 37 patients with extra-renal SLE, and 73 patients with LN. There were statistically significant differences in the GLS and LVMD between the extra-renal SLE and LN groups (GLS -19.36% vs. -17.61%, p < 0.001; LVMD 35.62 ms vs 42.96 ms, p<0.001). There was a statistically significant difference in the LVMD between the extral-renal SLE and control groups (35.62ms vs 25.51ms, p<0.001), but not in GLS (-19.36% vs -19.52%, p > 0.05). Multiple regression analyses were conducted in a subset of patients, and 24-hour proteinuria was independently associated with LVMD (β [SE], 0.793 [0.302], p < .05). CONCLUSIONS Patients with LN have more severe myocardial involvement than patients with extra-renal SLE. The asynchrony in myocardial contraction represented by the LVMD can be recognized earlier than that of the overall contractile functional impairment represented by GLS. In patients with LN, the 24-hour proteinuria was associated with LVMD. This indicates that the heterogeneity in the contractile function may be associated with the severity of renal damage.
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Affiliation(s)
- Wei He
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Peihan Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Wei Li
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Fengjuan Yao
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Yanqiu Liu
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Liuqin Liang
- Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
| | - Donghong Liu
- Department of Medical Ultrasonics, The First Affiliated Hospital, 71068Sun Yat-sen University, Guangzhou, China
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Abstract
Despite improvements in patient and renal death rates following the introduction of potent immunosuppressive drugs in earlier decades, a sizeable fraction of patients with lupus nephritis is burdened with suboptimal or delayed responses, relapses, chronic use of glucocorticoids and accrual of renal (chronic renal insufficiency) and extra-renal organ damage. The recently approved combinatory treatments comprising belimumab or voclosporin added to conventional agents, especially mycophenolate, hold promise for further improving disease outcomes and enabling a faster steroid tapering, thus being relevant to the treat-to-target context. However, it remains uncertain whether these dual regimens should become the first-line choice for all patients or instead be prioritized to certain subgroups. In the present article, we summarize the existing lupus nephritis management recommendations, followed by a critical appraisal of the randomized trials of belimumab and voclosporin, as well as the available data on obinutuzumab and other novel compounds under development. We conclude that pending the identification of accurate clinical, histological, or translational predictors for guiding personalized decisions, it is of utmost importance that lupus nephritis patients are monitored closely with appropriate treatment adjustments aiming at a prompt, deep response to ensure long-term preservation of kidney function.
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