Glomerular diseases最新文献

Primary membranous nephropathy is a common cause of adult-onset nephrotic syndrome, with an overall incidence of 12 cases per million per year. Primary membranous nephropathy is an autoimmune kidney disease; however, primary membranous nephropathy autoantigens remained elusive until 2009, when the M-type phospholipase A2 receptor 1 (PLA2R) was identified as a disease autoantigen. This was followed relatively rapidly by the identification of several other autoantigens. Autoantibodies against PLA2R are detectable in ≈75% of patients with primary membranous nephropathy. The discovery of circulating and deposited autoantibodies against PLA2R offers an opportunity in nephrology to personalize disease management. On January 14, 2023, NephCure Kidney International convened a scientific workshop in Arlington, Virginia, to discuss the state of the science on autoantibodies against PLA2R and considerations related to the incorporation of autoantibodies against PLA2R in drug development programs for membranous nephropathy. The present report captures the discussion that occurred at the Membranous Nephropathy Scientific Workshop.

Introduction: ANCA-associated vasculitis (AAV) and lupus nephritis (LN) are distinct disease processes that both cause a nephritic picture with acute kidney injury but have different pathophysiologies and thus different treatment strategies. They also have different characteristic phenotypes on kidney biopsy. Rarely, the two processes can coincide in one patient, known as AAV-LN overlap syndrome.

Case presentation: We present the case of a 78-year-old woman who presented with a rapidly progressive kidney injury and nephritic syndrome. Initial workup suggested AAV, but further serologies and ultimately a kidney biopsy demonstrated an overlap of both AAV and LN. Management was changed after discovery of this rare syndrome.

Conclusion: A low threshold for ordering serologies and early kidney biopsy are warranted in both AAV and LN as AAV-LN overlap has a unique management strategy that may respond to tailored treatment.

Introduction: Treating lupus nephritis is vital to reducing morbidity and mortality. In Thailand, comparative data on intravenous cyclophosphamide- and mycophenolate mofetil (MMF)-based induction therapies are limited. This study assessed renal remission outcomes for these regimens.

Methods: We analyzed renal and patient outcomes in 89 individuals with biopsy-proven active lupus nephritis treated at Phramongkutklao Hospital between 2020 and 2023. Among the cohort, 55 patients received a cyclophosphamide regimen, and 34 were treated with an MMF regimen.

Results: Baseline clinical characteristics were comparable between the two groups, except for higher hematuria and renal activity index, as well as lower C3 complement levels and renal chronicity in the cyclophosphamide group. The average doses administered were 0.55 ± 0.12 g/m² per dose for intravenous cyclophosphamide and 2.15 ± 0.31 g/day for MMF. By the 24th week, the overall remission rate (complete and partial remission) was 81.8% (45 patients) in the cyclophosphamide group and 85.3% (29 patients) in the MMF group (relative risk 1.01, 95% CI 0.82-1.23, p = 0.949). Proteinuria reduction from baseline at the 24th week was -54.1 ± 93.3% in the cyclophosphamide group and -69.4 ± 22.2% in the MMF group (relative risk 1.01, 95% CI 0.99-1.01, p = 0.465). Adverse events were similar across the two regimens. However, 1 patient in the cyclophosphamide group died, and three required dialysis.

Conclusion: Induction therapy with cyclophosphamide- and MMF-based regimens demonstrated comparable efficacy and safety in achieving renal remission in patients with active lupus nephritis.

Introduction: Systemic lupus erythematosus (SLE), as an autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women at fertile age. Late-onset SLE is defined as a disease onset over 45-50 years. Our main objective was to analyze the clinical, histological, prognostic, and therapeutic features related to LN in our late-onset SLE population.

Methods: A single-center and retrospective study was performed comparing clinical-demographic, histological, prognostic, and therapeutic features of 45 LN patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic onset (<45 years) and late onset (≥45 years).

Results: Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis, and higher Systemic Lupus Damage Index (SDI) score. Histology showed more nonproliferative LN classes (II and V). Late-onset LN responders, compared to those with classic onset, achieved response later. Nonresponsive patients had a higher incidence of acute kidney injury (AKI), more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, and a higher frequency for renal replacement therapy (RRT) at diagnosis and during follow-up. The main independent variables associated with relapse were younger age at SLE diagnosis and initial partial renal response (PRR).

Conclusions: Late-onset LN is often accompanied by other systemic autoimmune diseases such as Sjögren's and antiphospholipid syndrome. These patients have major cardiovascular comorbidities, poor estimated glomerular filtration rate (eGFR) at diagnosis, and increased chronicity index in histology. A tailored approach in this fragile population in order to avoid unnecessary immunosuppression is of critical interest.

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis.

Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023.

Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dL and 4.3 g/g, respectively. A detectable monoclonal (M) protein was detected in 28% of cases; however, only 3 patients had underlying hematologic disorders (multiple myeloma, CLL, and B-cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to end-stage kidney disease (ESKD), with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone-directed therapy.

Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are FDA-approved for weight loss and are increasingly prescribed for patients with obesity and type 2 diabetes mellitus. Multiple studies have demonstrated desirable renal and cardiovascular benefits from these novel agents. So far, a few case reports of acute tubular injury and acute interstitial nephritis have been reported with GLP-1RA. Podocytopathies in association with semaglutide are rare. In this case report, we present a case of nephrotic syndrome that developed after exposure to semaglutide and propose potential pathophysiological mechanisms underlying this rare renal complication.

Case presentation: Herein, we report a novel case of a 43-year-old female who was evaluated in the nephrology clinic for abrupt onset of bilateral lower extremity edema and foamy urine, a few weeks after exposure to semaglutide. She was diagnosed with nephrotic syndrome and subsequently underwent a kidney biopsy, which revealed features suggestive of minimal change disease, along with coexistent thin basement membrane disease.

Conclusion: GLP-1RAs have been increasingly prescribed due to their proven pleiotropic benefits, including improvements in albuminuria, glycemic control, weight loss, and cardioprotective effects. Despite the considerable benefits of GLP-1RAs, it is essential to recognize novel side effects.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have significantly impacted the management of diabetic kidney disease (DKD) and heart failure (HF), providing benefits beyond glycemic control. This review examines the mechanisms through which SGLT2is provide renal and cardiovascular protection and assesses their clinical efficacy.

Summary: By inducing glucosuria and natriuresis, SGLT2is alleviate multiple complications induced by chronic hyperglycemia. Moreover, SGLT2is reduce albuminuria, improve tubular function, and modulate erythropoiesis. Additionally, they mitigate inflammation and fibrosis by decreasing oxidative stress and downregulating proinflammatory pathways. Clinical trials have demonstrated significant reductions in renal and cardiovascular events among patients with type 2 diabetes mellitus. A comprehensive review of the literature was conducted through PubMed, highlighting the effects of SGLT2is and the results of major clinical trials involving SGLT2is.

Key messages: SGLT2is play a crucial role in the management of DKD and HF by addressing multiple pathogenic pathways. Currently, SGLT2is are included in clinical guidelines for DKD and HF management, and their benefits extend to nondiabetic populations. Further research is needed to explore SGLT2is' multifaceted mechanisms and potential applications across diverse patient populations and different disease etiologies.

Introduction: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear.

Case presentation: Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient's kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli.

Conclusion: These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.

Introduction: Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is associated with severe kidney failure and high morbidity and is exceedingly rare in children. The few pediatric studies published about this condition report dependency of kidney replacement therapy at presentation and partial or complete response in kidney function in a minority of cases.

Case presentation: We describe the case of a 14-year-old girl with crescentic glomerulonephritis based on double positive anti-GBM and myeloperoxidase-antineutrophil cytoplasmic antibodies with a mitigated clinical course presenting with fatigue, anemia, and an estimated glomerular filtration rate range between 34 and 42 mL/min/1.73 m². Response to treatment with daily therapeutic plasma exchanges, corticosteroids, and oral cyclophosphamide was prompt.

Conclusion: This ultrarare presentation highlights the need to consider determining anti-GBM antibodies and/or obtaining a kidney biopsy even in children with less severe presentations of unexplained glomerulonephritis and underlines the clinical treatment dilemma in this disease for children due to the potential long-term sequelae.