Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the NOBILITY Trial.

Objective: To determine whether adding obinutuzumab to standard-of-care lupus nephritis (LN) therapy could improve the likelihood of long-term preservation of kidney function and do so with less glucocorticoids.

Methods: Post hoc analyses of the phase II NOBILITY trial were performed. Time to unfavorable kidney outcome (a composite of treatment failure, doubling of serum creatinine, or death), LN flare, first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, and chronic eGFR slope during the trial were compared between patients with active LN who were randomized to take obinutuzumab (n = 63) or placebo (n = 62) in combination with mycophenolate mofetil and glucocorticoids.

Repeat kidney biopsy findings of lupus nephritis patients in clinical remission treated with Mycophenolate associated with Belimumab or Mycophenolate plus standard of care therapy. A "post-hoc" analysis of participants in the BLISS-LN and open label extension study belonging to a single center.

Background: Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes.

Research Design And Study Sample: In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response.

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial.

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.

Remission of lupus nephritis: the trajectory of histological response in successfully treated patients.

Objective: This study investigated changes in kidney histology over time in patients with lupus nephritis (LN) undergoing immunosuppressive treatment.

Methods: Patients with proliferative±membranous LN were studied. After a diagnostic kidney biopsy (Bx1), patients had protocol biopsy 2 (Bx2) at 9 (6-15) months and protocol biopsy 3 (Bx3) at 42 (28-67) months.

Molecular profiling of kidney compartments from serial biopsies differentiate treatment responders from non-responders in lupus nephritis.

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.

A Focus Group Study of Self-Management in Patients With Glomerular Disease.

Introduction: Patients with glomerular disease experience symptoms that impair their physical and mental health while managing their treatments, diet, appointments and monitoring general and specific indicators of health and their illness. We sought to describe the perspectives of patients and their care partners on self-management in glomerular disease.

Methods: We conducted 16 focus groups involving adult patients with glomerular disease ( = 101) and their care partners ( = 34) in Australia, Hong Kong, the United Kingdom, and United States.

A Core Outcome Set for Trials in Glomerular Disease: A Report of the Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) Stakeholder Workshops.

Background And Objectives: Outcomes reported in trials in adults with glomerular disease are often selected with minimal patient input, are heterogeneous, and may not be relevant for clinical decision making. The Standardized Outcomes in Nephrology-Glomerular Disease (SONG-GD) initiative aimed to establish a core outcome set to help ensure that outcomes of critical importance to patients, care partners, and clinicians are consistently reported.

Design, Setting, Participants, And Measurements: We convened two 1.

The lupus nephritis management renaissance.

Over the past year, and for the first time ever, the US Food and Drug Administration approved 2 drugs specifically for the treatment of lupus nephritis (LN). As the lupus community works toward understanding how to best use these new therapies, it is also an ideal time to begin to rethink the overall management strategy of LN. In addition to new drugs, this must include how to use kidney biopsies for management and not just diagnosis, how molecular technologies can be applied to interrogate biopsies and how such data can impact management, and how to incorporate LN biomarkers into management paradigms.

B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial.

Objective: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies.

Methods: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104.

A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis.

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more.

Development of an international Delphi survey to establish core outcome domains for trials in adults with glomerular disease.

Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glomerular disease, caregivers and health professionals aged 18 years and older rated the importance of outcomes using a Likert scale and a Best-Worst scale.

A Novel Inflammatory Dendritic Cell That Is Abundant and Contiguous to T Cells in the Kidneys of Patients With Lupus Nephritis.

The mechanisms that promote local inflammatory injury during lupus nephritis (LN) flare are largely unknown. Understanding the key immune cells that drive intrarenal inflammation will advance our knowledge of disease pathogenesis and inform the development of new therapeutics for LN management. In this study, we analyzed kidney biopsies from patients with proliferative LN and identified a novel inflammatory dendritic cell (infDC) population that is highly expressed in the LN kidney, but minimally present in healthy human kidneys.

Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis.

Background: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown.

Methods: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.

Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers.

Background And Objectives: Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices.

Design: We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States.

Podocyte infolding glomerulopathy; report of the first case in Latin America and review of the literature.

Background: Podocyte infolding glomerulopathy (PIG) is a condition of uncertain origin, frequently associated with autoimmune diseases. Its specific treatment and clinical course are unknown. It is characterised by thickening of the capillary walls due to the presence of non-argyrophilic intramembranous bubbles similar to those found in membranous glomerulopathy, but without electron-dense deposits of immune complexes in the ultrastructure, where translucent microspheres generated by invagination of the podocyte cytoplasm into the basement membranes are observed.

Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis.

The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares.

Rethinking Lupus Nephritis Classification on a Molecular Level.

The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. Integration of molecular classifiers into histologic evaluation can improve diagnostic precision and identify therapeutic targets. This study described the relationship between histological and molecular phenotypes and clinical responses in LN.

Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy.

Background: Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease ('secondary IgAN') or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)].

Reimagining the kidney biopsy in the era of diagnostic biomarkers of glomerular disease.

Anti-phospholipase A2 receptor (PLA2R) antibody is a specific biomarker for primary membranous nephropathy (MN). Testing positive for anti-PLA2R has been postulated to establish a diagnosis of MN in the absence of a kidney biopsy. Bobart et al.

Molecular imaging of the kidney in lupus nephritis to characterize response to treatment.

The consequences of treatment for the kidney at the molecular level have not been explored in human lupus nephritis (LN). In this investigation, changes in intrarenal transcript expression were measured and correlated with response in a LN cohort that underwent serial kidney biopsies. The intrarenal transcript expression of 19 patients with proliferative LN (Class III or IV) was measured at diagnostic biopsy (Bx1) and after induction therapy was completed (Bx2) using Nanostring technology.

Characterising the immune profile of the kidney biopsy at lupus nephritis flare differentiates early treatment responders from non-responders.

Introduction: The kidney biopsy is used to diagnose and guide initial therapy in patients with lupus nephritis (LN). Kidney histology does not correlate well with clinical measurements of kidney injury or predict how patients will respond to standard-of-care immunosuppression. We postulated that the gene expression profile of kidney tissue at the time of biopsy may differentiate patients who will from those who will not respond to treatment.

The Kidney Biopsy in Lupus Nephritis: Past, Present, and Future.

Since its incorporation into clinical practice in the 1950s, the percutaneous kidney biopsy has played an important role in advancing our understanding of lupus nephritis (LN). The biopsy findings have been used to classify and subgroup LN in order to obtain an accurate diagnosis and also to inform treatment decisions and predict prognosis. Several classifications schemes have been applied clinically however despite this evolution in histopathologic classification, our ability to predict treatment response and determine prognosis remains limited.