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      Lupus nephritis: clinical presentations and outcomes in the 21st century

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          Abstract

          Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.

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          Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

          Michelle Petri, Ana-Maria Orbai, Graciela Alarcón … (2012)
          The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies. Copyright © 2012 by the American College of Rheumatology.
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            2019 update of the EULAR recommendations for the management of systemic lupus erythematosus

            Antonis Fanouriakis, Myrto Kostopoulou, Alessia Alunno … (2019)
            Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
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              2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus

              Martin Aringer, Karen H Costenbader, David I. Daikh … (2019)
              To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Rheumatology (Oxford)
                Journal ID (iso-abbrev): Rheumatology (Oxford)
                Journal ID (publisher-id): brheum
                Title: Rheumatology (Oxford, England)
                Publisher: Oxford University Press
                ISSN (Print): 1462-0324
                ISSN (Electronic): 1462-0332
                Publication date Collection: December 2020
                Publication date (Electronic): 05 December 2020
                Publication date PMC-release: 05 December 2020
                Volume: 59
                Issue: Suppl 5 , Lupus in the 21st Century
                Pages: v39-v51
                Affiliations
                [1 ] Rheumatology Unit, Department of Medicine, University of Padua
                [2 ] Nephrology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico , Milan, Italy
                Author notes

                Gabriella Moroni and Andrea Doria contributed equally to this manuscript.

                Correspondence to: Andrea Doria, Division of Rheumatology, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. E-mail: adoria@ 123456unipd.it
                Author information
                http://orcid.org/0000-0003-0548-4983
                Article
                Publisher ID: keaa381
                DOI: 10.1093/rheumatology/keaa381
                PMC ID: 7751166
                PubMed ID: 33280015
                SO-VID: 74ff4f8f-29ea-4e92-aa9d-cb5578c905f9
                Copyright © © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Date received : 22 April 2020
                Date accepted : 28 May 2020
                Page count
                Pages: 13
                Funding
                Funded by: GSK, DOI 10.13039/100004330;
                Categories
                Subject: Supplement Papers
                Subject: AcademicSubjects/MED00360

                ScienceOpen disciplines: Rheumatology
                Keywords: lupus nephritis,renal biopsy,classification,risk factors,prognosis,b cells,calcineurin inhibitors
                Data availability:
                ScienceOpen disciplines: Rheumatology
                Keywords: lupus nephritis, renal biopsy, classification, risk factors, prognosis, b cells, calcineurin inhibitors

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