Lupus Nephritis

BACKGROUND: Data on belimumab efficacy in patients with lupus nephritis (LN) according to diagnosis duration or induction therapy are limited. Post hoc analyses of the phase 3, randomized, double-blind BLISS-LN study (GSK BEL114054; NCT01639339) were performed to assess belimumab efficacy on kidney-related outcomes in newly diagnosed and relapsed LN subgroups and according to the use of glucocorticoid (GC) pulses at induction. METHODS: BLISS-LN randomized 448 patients with active LN to monthly intravenous belimumab 10 mg/kg or placebo plus standard therapy...

The past few years have provided important insights into the genetic architecture of systemic autoimmunity through aggregation of findings from genome-wide association studies (GWAS) and whole-exome or whole-genome sequencing studies. In the prototypic systemic autoimmune disease systemic lupus erythematosus (SLE), monogenic disease accounts for a small fraction of cases but has been instrumental in the elucidation of disease mechanisms. Defects in the clearance or digestion of extracellular or intracellular DNA or RNA lead to increased sensing of nucleic acids, which can break B cell tolerance and induce the production of type I interferons leading to tissue damage...

Kidney involvement in patients with systemic lupus erythematosus - lupus nephritis (LN) - is one of the most important and common clinical manifestations of this disease and occurs in 40-60% of patients. Current treatment regimens achieve a complete kidney response in only a minority of affected individuals, and 10-15% of patients with LN develop kidney failure, with its attendant morbidity and considerable prognostic implications. Moreover, the medications most often used to treat LN - corticosteroids in combination with immunosuppressive or cytotoxic drugs - are associated with substantial side effects...

OBJECTIVE: To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN). METHODS: 121 patients were randomized (2:1:1:2) to placebo or BI 655064 120mg, 180mg or 240mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120mg and 180mg groups, and 120mg weekly for the 240mg group...

The National Institutes of Health (NIH) lupus nephritis activity and chronicity indices, which comprise six activity scores and four chronicity scores, have a long development history. The 2018 revised International Society of Nephrology/Renal Pathology Society classification for lupus nephritis adopted the most recent NIH indices to replace subclasses A, C, and A/C. Although an evidence-based approach should further evaluate the clinical significance of the modified NIH indices, recent validation studies demonstrated that the modified chronicity indices have a strong correlation with kidney outcome of lupus nephritis...

PURPOSE OF REVIEW: The ISN/RPS lupus nephritis classification is in the process of undergoing a revision. It has lost its way and morphed from a classification based on pathophysiology of disease into a staging system based on the extent of spread and prognosis. RECENT FINDINGS: There are multiple different pathophysiologic processes that contribute to lupus nephritis. The current classification is inadequate, as it does not highlight these differences and thus squanders the opportunity to develop targeted therapies...

Multiple autoantigens have been identified in membranous nephropathy (MN) by tissue-based proteomics. However, antigenic targets of disease are unknown for over 10% of patients with MN and over half of those with membranous lupus nephritis (MLN). Here, we identified multiple new targets in PLA2R-/THSD7A-/EXT-/NELL1-quadruple negative MN biopsies through mass spectrometry of immune complexes recovered from biopsy tissue of patients with MN. Patients with MN negative for these four antigens were identified from Arkana Laboratories case archives...

INTRODUCTION: Proliferative lupus nephritis (LN) progresses to end-stage kidney disease (ESKD) in roughly 10% of the cases despite treatment. Other than achieving <0.8 g/24h proteinuria at 12 months after treatment, early biomarkers predicting ESKD or death are lacking. Recent studies encompassing not only LN have highlighted the central role of the alternative complement pathway (ACP), with or without histological evidence of thrombotic microangiopathy (TMA), as a key promotor of renal death...

BACKGROUND: Overall survival of systemic lupus erythematosus (SLE) patients significantly increased in recent decades, however, the relative risk of mortality is still high. Long-term survival outcome of pediatric SLE remains unclear. This study aims to explore the long-term survival rate and its predictors in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective, hospital-based cohort study was performed between 2004 and 2018 in a tertiary referral medical center in Taiwan...

OBJECTIVES: Class IV lupus nephritis (LN) is one of the most frequent and severe types of involvement in pediatric systemic lupus erythematosus. Gold standard treatment consists of intravenous (i.v.) Cyclophosphamide (CYC) associated with corticosteroids. Recent studies in adults have shown similar efficacy of oral Mycophenolate Mofetil (MMF) with fewer adverse events. Our aim was to compare the efficacy and tolerance of CYC and MMF as induction therapy in children with class IV LN...

BACKGROUND: The familial clustering phenomenon together with environmental influences indicates the presence of a genetic and epigenetic predisposition to systematic lupus erythematosus (SLE). Interestingly, regarding lupus nephritis (LN), the worst complication of SLE, mortality, and morbidity were not consistent with SLE in relation to sexuality and ethnicity. SUMMARY: Genetic and epigenetic alterations in LN include genes and noncoding RNAs that are involved in antigen-presenting, complements, immune cell infiltration, interferon pathways, and so on...

Current immunosuppression regimens for lupus nephritis are incompletely effective, placing patients at risk for poor long-term outcomes. This emphasizes the need to dissect pathogenic mechanisms in lupus nephritis, to inform the development of targeted therapies. In this issue of Kidney International, Parikh et al. performed transcriptomic analysis of pretreatment and posttreatment protocol kidney biopsies, segregated into glomerular and tubulointerstitial compartments, to identify candidate molecular pathways distinguishing treatment responders and nonresponders...

OBJECTIVE: This integrated analysis evaluates the efficacy and safety of voclosporin, a novel calcineurin inhibitor, at 23.7 mg twice daily in combination with mycophenolate mofetil (MMF) and oral glucocorticoids in lupus nephritis (LN) using pooled data from two large phase II and phase III clinical trials. The purpose was to expand the pool of patients for safety analyses and to increase power for efficacy analyses in patient subpopulations. METHODS: Aurinia Urinary Protein Reduction in Active Lupus with Voclosporin (AURA-LV) (phase II) and Aurinia Renal Response in Active Lupus With Voclosporin (AURORA 1) (phase III) were randomized, placebo-controlled, double-blind trials with similar designs and end points comparing voclosporin to control in combination with MMF and oral glucocorticoids for the treatment of LN...

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...

The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-kidney pathways, transcriptomic analysis was done on protocol kidney biopsies obtained at flare (initial biopsy (Bx1)) and after treatment (second biopsy (Bx2)) in 58 patients with LN. Glomeruli and tubulointerstitial compartments were isolated using laser microdissection. RNA was extracted and analyzed by nanostring technology with transcript expression from clinically complete responders, partial responders and non-responders compared at Bx1 and Bx2 and to the healthy controls...

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...

PURPOSE OF REVIEW: Renal involvement in patients with systemic lupus erythematosus can lead to significant complications including end-stage renal disease. Treatment of lupus nephritis has evolved over the last several decades, but despite this evolution, many patients fail to achieve remission and often progress to end-stage kidney disease or carry a burden of adverse side effects related to treatment. RECENT FINDINGS: The recent findings from AURORA 1 and BLISS LN trials led the FDA to approve voclosporin and belimumab for the treatment of lupus nephritis...

This post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN) shows belimumab effectively reduced the time to 30% and 40% decreases in estimated glomerular filtration rate and persistent decreases in estimated glomerular filtration rate. Subgroup analysis found belimumab was most effective in proliferative lupus nephritis, and that there was no apparent benefit from the addition of belimumab in those with baseline nephrotic range proteinuria nor in those receiving cyclophosphamide/azathioprine...

BACKGROUND AND OBJECTIVES: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death...

Approximately 70% of the patients with systemic lupus erythematosus will have clinical evidence of kidney damage during their evolution. Patients with impaired renal function at onset and those with recurrent flares have a poor prognosis. Understanding the mechanism of action of immunosuppressants is essential for proper prescription. Steroids inhibit the DNA sequence that promotes the release of inflammatory cytokines. Phosphoramide mustard, metabolite of cyclophosphamide, cross-link with the DNA, causing the aggregation of an alkyl group, causing cell death...