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Kidney International Apr 2018We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting...
Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.
We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. We also eliminate the class IV-S and IV-G subdivisions of class IV lupus nephritis. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. In the activity index, we include fibrinoid necrosis as a specific descriptor. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). We propose to proceed to these investigations, with clinicopathologic studies and tests of interobserver reproducibility to evaluate the applications of the proposed definitions and to classify lupus nephritis lesions.
Topics: Biopsy; Chronic Disease; Consensus; Humans; Kidney Glomerulus; Lupus Nephritis; Predictive Value of Tests; Prognosis; Severity of Illness Index; Terminology as Topic
PubMed: 29459092
DOI: 10.1016/j.kint.2017.11.023 -
Clinical Journal of the American... May 2017SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in... (Review)
Review
SLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for lupus nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with lupus.
Topics: Biopsy; Disease Progression; Genetic Predisposition to Disease; Humans; Kidney; Kidney Failure, Chronic; Lupus Nephritis; Phenotype; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 27821390
DOI: 10.2215/CJN.05780616 -
Rheumatology (Oxford, England) Dec 2020Lupus 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,... (Review)
Review
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.
Topics: Disease Progression; Humans; Lupus Nephritis; Prognosis; Recurrence; Remission Induction; Risk Factors
PubMed: 33280015
DOI: 10.1093/rheumatology/keaa381 -
The Journal of Applied Laboratory... Oct 2022Lupus nephritis (LN) is one of the most common severe organ manifestations of systemic lupus erythematosus (SLE). LN is associated with significant morbidity and... (Review)
Review
BACKGROUND
Lupus nephritis (LN) is one of the most common severe organ manifestations of systemic lupus erythematosus (SLE). LN is associated with significant morbidity and mortality in SLE patients, as up to 20% of patients progress to end-stage renal disease (ESRD). The clinical manifestations of LN are variable, ranging from asymptomatic proteinuria to a myriad of manifestations associated with nephritic and nephrotic syndromes and ESRD. It is therefore important to screen all SLE patients for LN.
CONTENT
Urinalysis is a useful screening test in LN. Quantification of proteinuria can be performed with either a urine protein-to-creatinine ratio or 24-h urine sample collection for protein. Renal biopsy remains the gold standard for diagnosis of LN. Traditional serum biomarkers used to monitor SLE and LN disease activity and flares include anti-double-stranded DNA antibodies and complement components 3 and 4. Other nonconventional biomarkers found to correlate with LN include anti-C1q and surrogate markers of type 1 interferon regulatory genes (INF gene signature). Potential urinary biomarkers for LN include monocyte chemoattractant protein 1, neutrophil gelatinase-associated lipocalin, tumor necrosis factor-like inducer of apoptosis, and vascular cell adhesion molecule 1.
SUMMARY
Although studies have shown promising results for the use of alternative biomarkers, these require validation in prospective studies to support their use. Renal remission rates in patients receiving standard of care therapy for induction and maintenance treatment of LN remain low. This has prompted further research in newer therapeutic targets in LN ,which have shown promising results.
Topics: Humans; Lupus Nephritis; Prospective Studies; Lupus Erythematosus, Systemic; Biomarkers; Proteinuria; Kidney Failure, Chronic
PubMed: 35932197
DOI: 10.1093/jalm/jfac036 -
Journal of the American Society of... Sep 2013Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms.... (Review)
Review
Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies.
Topics: Antibodies, Antinuclear; Humans; Interferon-alpha; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphocytes; Signal Transduction
PubMed: 23929771
DOI: 10.1681/ASN.2013010026 -
Jornal Brasileiro de Nefrologia 2019Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is... (Review)
Review
Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is more frequent and severe in pediatric patients and has been associated with higher morbidity and mortality rates. This narrative review aimed to describe the general aspects of LN and its particularities when affecting children and adolescents, while focusing on the disease's etiopathogenesis, clinical manifestations, renal tissue alterations, and treatment options.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Early Diagnosis; Female; Humans; Infant; Infant, Newborn; Lupus Nephritis; Male; Prevalence; Rare Diseases
PubMed: 30465590
DOI: 10.1590/2175-8239-JBN-2018-0097 -
Seminars in Nephrology Jul 2017Pregnancy associated with lupus, especially lupus nephritis, is often fraught with concern for both the mother and fetus. Thus, it is paramount that care begins... (Review)
Review
Pregnancy associated with lupus, especially lupus nephritis, is often fraught with concern for both the mother and fetus. Thus, it is paramount that care begins preconception so that proper planning in terms of optimizing the medical regimen, discontinuation of fetotoxic agents, and treatment of active disease can occur. It is well known that active nephritis at the time of conception is associated with poor outcomes. Even with quiescent disease, recent data indicate that being lupus anticoagulant-positive, nonwhite or Hispanic, and using antihypertensive medications were all predictors of worse pregnancy outcomes. Further, prior lupus nephritis also predicts higher rates of preeclampsia and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Differentiating lupus nephritis from preeclampsia often presents as a conundrum, but lupus nephritis can be confirmed by the presence of decreasing complement levels and increasing double-stranded DNA (dsDNA) antibody levels in addition to new onset hypertension and proteinuria. We hope that the more mechanistic approach of measuring angiogenic markers, which are diagnostic for preeclampsia, will be the standard of care in the future. Women with lupus and prior lupus nephritis can have successful pregnancies, but outcomes are dependent on "the art of planning" as well as close communication between the obstetrician, the nephrologist, and the rheumatologist.
Topics: Diagnosis, Differential; Female; Humans; Lupus Nephritis; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Symptom Flare Up
PubMed: 28711073
DOI: 10.1016/j.semnephrol.2017.05.006 -
Advances in Chronic Kidney Disease Sep 2019In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus... (Review)
Review
In systemic lupus erythematosus, nephrotic-range proteinuria typically signals the presence of a proliferative lupus nephritis (class III/IV) and/or membranous lupus nephritis (class V, with or without concomitant class III or IV lesions). However, in rare instances, systemic lupus erythematosus patients with nephrotic syndrome have kidney biopsy findings of normal glomeruli or focal segmental glomerulosclerosis lesions, with or without mesangial proliferation, on light microscopy; the absence of subepithelial or subendothelial deposits on immunofluorescence and electron microscopy; and diffuse foot process effacement on electron microscopy. This pattern, termed lupus podocytopathy, is a unique form of lupus nephritis that mimics minimal change disease or primary focal segmental glomerulosclerosis and represents approximately 1% of lupus nephritis biopsies. Here we review the clinical features, histological manifestations, diagnostic criteria and classification, pathogenesis, treatment, and prognosis of lupus podocytopathy.
Topics: Disease Management; Humans; Kidney Glomerulus; Lupus Erythematosus, Systemic; Lupus Nephritis; Nephrotic Syndrome; Podocytes
PubMed: 31733721
DOI: 10.1053/j.ackd.2019.08.011 -
Rheumatology (Oxford, England) Dec 2020The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on... (Review)
Review
The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on molecular approaches and the results from large studies using polyomics may be interpreted as demonstrating the relevance of the genetic and environmental background rather than splitting SLE into several entities. In fact, an association study within the EULAR/ACR classification criteria project found associations between manifestations only within organ domains. This independency of various organ manifestations argues for SLE as one disease entity. The current review article will therefore concentrate on the clinical and immunological manifestations of SLE and on what we have already learned in this century. Moreover, the structure and essential rules of the EULAR/ACR 2019 classification criteria will be discussed. While classification and diagnosis are distinct concepts, which have to remain clearly separated, information derived from the process towards the classification criteria is also useful for diagnostic purposes. Therefore this article also tries to delineate what classification can teach us for diagnosis, covering a wide variety of SLE manifestations.
Topics: Antibodies, Antinuclear; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Musculoskeletal System; Skin
PubMed: 33280013
DOI: 10.1093/rheumatology/keaa379 -
Lupus Science & Medicine 2020Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting... (Review)
Review
Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.
Topics: Artificial Intelligence; Biomarkers; Biopsy; Female; Humans; Immunosuppression Therapy; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Outcome Assessment, Health Care; Patient Outcome Assessment; Prognosis; Renal Insufficiency
PubMed: 32153796
DOI: 10.1136/lupus-2020-000389