Molecular Markers of Injury in Kidney Biopsy Specimens of Patients with Lupus Nephritis (original) (raw)
Related papers
The pathogenesis, diagnosis and treatment of lupus nephritis
Current opinion in rheumatology, 2014
Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus. In this review, we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis. Localized long-lived plasma cells have been identified as playing an important role in lupus nephritis. In addition, the roles of aberrant expression of microRNAs and proinflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none has been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of lupus nephritis are being studied, including belimumab which was recently approved for nonrenal systemic lupus erythematosus. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of lupus nephritis. Lupus nephritis is a pot...
Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue
International Journal of Molecular Sciences, 2015
The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy.
Urinary cytokines and mRNA expression as biomarkers of disease activity in lupus nephritis
Lupus, 2018
Introduction: Renal involvement is one of the most serious manifestations of systemic lupus erythematosus, but non-invasive assessment of inflammatory response in kidneys is challenging. In this study we aimed to validate markers of active lupus nephritis (LN) using urine immune profiling. Methods: Urine and serum cytokines (17-plex array) and urine mRNA expression ($40 immune and glomerular injury genes) were measured in LN patients with active disease (n ¼ 17) during remission (n ¼ 16) and in healthy subjects (n ¼ 18). Results: Urine and serum levels of CCL2, CCL5 and CXCL10 were elevated in active LN as compared with disease remission (best discrimination for urine CXCL10 and CCL2) and correlated with LN activity. In the active disease, urinary cell transcriptome showed marked upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), and type-1 immunity-related genes (e.g. CD3G, CD4, TBX21, IFNG). An active pattern of gene expression was also observed in four patients in remission, who had moderately increased urinary leucocyte count. Two patients from this group developed renal exacerbation during the following 3 months. Markers of type-17 immune axis (e.g. IL-17A) were not significantly increased in active LN. Conclusions: Active LN patients were characterized by marked increase of proinflammatory mediators in the urine. Urine cytokines (CCL2 and CXCL10) and type-1 T-cell-related gene markers in the urine sediment had similar diagnostic performance in detection of active LN. Lupus (2018) 0, 1-12.
Update on Lupus Nephritis: Looking for a New Vision
Nephron, 2020
Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), affecting approximately 40% of patients with lupus. It represents a major risk factor for morbidity and mortality, and 10% of patients with LN will develop end-stage kidney disease (ESKD). Therefore, there are a number of areas for improvement in the field of LN such as the search for new clinical biomarkers with a more accurate correlation with lupus activity and the redefinition of the histological classification into different subgroups in order to guide a personalized treatment. Although the role of protocol repeat kidney biopsies in LN is controversial, recent publications suggest that repeat histological assessment can be useful in guiding therapeutic decisions that may yield toward precision medicine. In the last decade, LN therapy has remained largely unchanged, with a probability of achieving complete or partial remission not exceeding 60–70%. Thus, optimization of old treat...
Lupus Nephritis: Pathogenesis and Treatment Update Review
Open Science Journal, 2021
Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). LN is a leading cause of morbidity and mortality in SLE patients. LN presents with various symptoms and signs, ranging from asymptomatic renal involvement to End- Stage Renal Disease (ESRD). The pathogenesis of LN is not clearly understood, however, there are extra and intra-renal underlying factors that have been postulated in LN pathogenesis. Renal biopsy is crucial to stage LN and to rule out other causes. Histopathological studies have shown six different types of LN. Knowing the histopathological lesion, chronicity, and disease activity are essential to plan the LN treatment and to predict the outcome. There are different regimens for treating LN. In this review, LN pathogenesis and new advances in treatment will be briefly reviewed.
The Journal of Rheumatology, 2012
Objective.To study the role of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/Fn14 and the interferon-inducible protein (IP-10)/CXCR3 axis in lupus nephritis (LN).Methods.We studied 113 patients with LN who had had repeat renal biopsies. Glomerular and tubulointerstitial messenger RNA expression of TWEAK, Fn14, IP-10, and CXCR3 were quantified.Results.Glomerular Fn14 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.016), and increased when changed from membranous to proliferative or mixed nephritis (p = 0.0006). On the other hand, tubulointerstitial TWEAK expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.004), and increased when changed from membranous nephropathy to proliferative nephritis (p = 0.010). Tubulointerstitial IP-10 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p < 0.0001). Histological ...
Lupus Nephritis: Clinical Picture, Histopathological Diagnosis, and Management
IntechOpen eBooks, 2023
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost every organ of the body and presents with a great variety of clinical features. SLE effect on kidneys, mostly referred to as lupus nephritis, is of special interest for the rheumatologist and nephrologist for three reasons. First, lupus nephritis is one of the commonest types of organ involvement in this disorder, affecting as up to 45% of all patients with SLE. Second, it presents with a great variety of clinical and histopathological findings, and thus, therapy must be tailored accordingly. Third, it greatly affects the morbidity and mortality of SLE patients. Taking these facts into account, this chapter is centered on lupus nephritis from the perspective of the clinical nephrologist and renal pathologist. This chapter elaborates the diversity of clinical features of lupus nephritis, in relation to the different histopathological forms of the disease and the therapeutic options that are available to date, as well as the pathogenesis, natural history, and prognosis of patients with lupus nephritis.
A composite urine biomarker reflects interstitial inflammation in lupus nephritis kidney biopsies
Kidney International, 2012
The initial treatment of lupus nephritis is usually based on a renal biopsy. Subsequent disease flares, however, are often treated without the benefit of kidney pathology because repeat biopsies are infrequent. A noninvasive, real-time method to assess renal pathology would be useful to adjust treatment and improve outcome. To develop such a method we collected urine samples at or close to the time of 64 biopsies from 61 patients with lupus nephritis to identify potential biomarkers of tubulointerstitial inflammation and correlated these to biopsy parameters scored by a renal pathologist using a semiquantitative scale. Linear discriminant analysis was used to weight variables and derive composite biomarkers that identified the level of tubulointerstitial inflammation based on urine concentrations of monocyte chemotactic protein-1, hepcidin (a marker of active lupus), and liver fatty acid-binding protein. The discriminant function that described the most accurate composite biomarkers included urine monocyte chemotactic protein-1 and serum creatinine as the independent variables. This composite had sensitivity, specificity, positive predictive value, and negative predictive value of 100, 81, 67, and 100%, respectively. Only 14% of the biopsies were misclassified. Thus, specific renal pathologic lesions can be modeled by composite biomarkers to noninvasively follow and adjust the treatment of lupus nephritis reflecting renal injury.
Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions
Lupus, 2010
Systemic lupus erythematosus may present with renal manifestations that frequently are difficult to categorize and lupus nephritis is an important predictor of poor outcome. The type and spectrum of renal injury may remain undiagnosed until full-blown nephritic and/or nephrotic syndrome appear with increased risk of end-stage renal disease. These abnormalities occur within the first few years after the diagnosis of lupus is made on clinical grounds and with the support of laboratory tests in high risk patients. An early renal biopsy is helpful in patients with an abnormal urinalysis and/or reduced glomerular filtration rate and the results form the basis for therapeutic decisions. The biopsy also provides vital prognostic information based on histological categorization of different types of lupus nephritis, the degree of activity, chronicity and the immunopathogenesis. In the current armamentarium, the use of cyclophosphamide and azathioprine and recently mycophenolate mofetil, red...
Top 10 Developments in Lupus Nephritis
Current Rheumatology Reports, 2013
Lupus nephritis affects up to 60 % of patients with systemic lupus erythematosus and is associated with worse clinical outcomes. Traditionally, it has been treated with high-dose immunosuppression consisting of cyclophosphamide and prednisone; however, recent trials have demonstrated mycophenolate mofetil as a safe and effective alternative for both induction and maintenance of disease. Other progress has been made in our understanding of the pathogenesis of lupus nephritis, outcomes in renal transplantation, and associations with genetic risk factors. This review highlights key developments in our understanding of lupus nephritis over the past decade.