一次性ネフローゼ症候群

Membranous nephropathy (MN) is a common cause of idiopathic nephrotic syndrome in adults. The identification of the phospholipase A2 receptor 1 (PLA2R) as a podocyte antigen in adult patients with MN allows clinicians to quickly and accurately diagnose primary MN. Secondary forms associated with malignancy, medications, infection, or autoimmune disease do not generally express anti-PLA2R autoantibodies. We describe a case of a 66-year-old woman who presented with impure nephrotic syndrome, and a renal biopsy showed MN. The diagnosis of secondary MN was initially retained despite positive Anti- PLA2R in light of the discovery of a pulmonary adenocarcinoma. However, nephrotic syndrome persisted after surgical treatment and tumor remission. Remission was only achieved after the use of immunosuppressive therapy. Our case teaches us that even in the presence of an evident etiology for MN, the diagnosis of primary form should always be reconsidered in the absence of remission, especially when anti-PLA2R antibodies are positive.

INTRODUCTION: Kidney outcomes in children with steroid-resistant nephrotic syndrome (SRNS) following rituximab remain unclear. METHODS: We conducted an international retrospective cohort study across 23 centers in 17 countries, including children with SRNS who did not respond to calcineurin inhibitors (CNIs) and subsequently, received rituximab. Patients with genetic variants were excluded. The primary outcome was kidney survival. RESULTS: We analyzed data on 151 children (53% males; median age at onset: 6.8 years; primary vs. secondary SRNS: 54% vs. 46%; focal segmental glomerulosclerosis [FSGS]: 62%). All subjects received CNIs before rituximab (0-3 months: 21%; 3-6 months: 26%; 6-12 months: 26%; > 12 months: 26%). Upon rituximab, 73 subjects (48%) had normal kidney function, 47 (31%) had chronic kidney disease (CKD)2, and 31 (21%) had CKD3. Twenty-eight (19%) developed kidney failure. Overall kidney survival was 82.7%, 75.8%, and 72.3% at 3, 5, and 7 years post-rituximab. Baseline CKD staging before rituximab was associated with kidney survival at 5 years (log-rank P < 0.001); CKD stage 1, 91.7%; CKD stage 2, 70.4%; and CKD stage 3, 35.5%). The predictive factors for inferior kidney survival were CKD2 (adjusted hazard ratio [HRadj]: 2.7, 95% confidence interval [CI]: 1.5-4.9, P < 0.001), lower baseline serum albumin (log-rank P = 0.01; HRadj: 0.88, 95% CI: 0.81-0.95; P < 0.001) and FSGS (log-rank P = 0.03; HRadj: 3.4, 95% CI: 1.1-10.0; P < 0.001). Nonremission at 6 months was associated with inferior kidney survival (61.2% at 5 years), compared with complete remission (CR) or partial remission (PR) (100% at 5 years) (log-rank P = 0.01; HRadj: 14.1, 95% CI: 2.2-93.5, P = 0.01). Duration of prior calcineurin inhibition and SRNS type were not significant predictors. CONCLUSION: Kidney survival of SRNS following add-on rituximab is 70% to 80% over 3 to 7 years. Nonresponse, preexisting CKD, lower albumin, and FSGS predict inferior kidney survivals.

BACKGROUND: Rituximab is increasingly used to treat childhood nephrotic syndrome, although its long-term effects are poorly understood. Our study aims to evaluate the incidence and risk factors for hypogammaglobulinemia, hematological complications, B cell repopulation, and relapses after rituximab treatment. METHODS: We included children (1-18 years of age) with nephrotic syndrome who were enrolled in a prospective cohort study (Greater Toronto Area, Canada) and received rituximab from June 2018 to December 2023. We collected all immunoglobulin, hematology, and microbiology results from our institution. The primary outcome was hypogammaglobulinemia (IgG ≥ 2 standard deviations below the age-specific mean), classified as severe (IgG < 3 g/L) and/or prolonged (≥ 12 months). Secondary outcomes included other immunoglobulin and hematological parameters, B cell depletion, and relapses. RESULTS: Seventy children with nephrotic syndrome received rituximab treatment. Pre-existing hypogammaglobulinemia was present in 46% of the patients. After rituximab, 68% of the patients had any, 32% had severe, and 46% had prolonged hypogammaglobulinemia. Younger age (odds ratio [OR] 1.13, 95% CI 1.01-1.29), European ethnicity (OR 6.37, 95% CI 1.74-30.83), lower pre-treatment IgG (OR 1.63, 95% CI 1.24-2.31) and longer maintenance immunosuppression duration (OR 1.27, 95% CI 1.03-1.61) were risk factors for prolonged hypogammaglobulinemia post-rituximab. Post-rituximab, 16% of the children had anemia, 21% had neutropenia, and 3% had thrombocytopenia. Twelve children (17%) developed documented infections. All children experienced complete B cell depletion post-rituximab, with B cell repopulation at median 6.3 months. Older age, prior calcineurin inhibitor treatment, and steroid sensitivity were associated with longer time-to-B cell repopulation. CONCLUSIONS: Prolonged hypogammaglobulinemia occurs in half of children with nephrotic syndrome post-rituximab. Younger age, European ethnicity, lower pre-treatment IgG, and longer maintenance immunosuppression use are associated with higher prolonged hypogammaglobulinemia risk.

Membranous Nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, characterized by significant clinical heterogeneity ranging from spontaneous remission to end-stage kidney disease. Current management of membranous nephropathy, which relies heavily on renal biopsy and static serological markers such as anti-PLA2R antibodies, often fails to predict individual disease trajectories. This limitation frequently leads to empirical immunosuppressive therapy with a trial-and-error approach. This review explores the transformative potential of Artificial Intelligence (AI) in reshaping MN management from evidence-based to data-driven and predictive medicine. We examine AI-driven innovations across the clinical spectrum: from computational pathology systems that automate glomerular morphometry with high objectivity and reproducibility, to non-invasive diagnostic models integrating radiomics and serology for non-invasive diagnosis. In therapeutics, we discuss machine learning algorithms that predict individual responses to Rituximab versus Cyclophosphamide, enabling personalized regimen selection. Furthermore, we highlight the role of AI in prognostic stratification, where dynamic in silico patient models and multi-omics integration unravel molecular subtypes and forecast renal survival with high granularity. While acknowledging critical challenges such as data silos, model interpretability gaps, and the need for global validation, we conclude that AI serves as a powerful augmentation tool. By synthesizing high-dimensional data into actionable insights, AI has the potential to facilitate increasingly predictive, preventative, and personalized care strategies in MN management.

BACKGROUND: There has been an annual rise in the incidence of primary membranous nephropathy (PMN), a common pathological type of nephrotic syndrome (NS). Obinutuzumab is a humanised, glycosylated, type II anti-CD20 monoclonal antibody. Characterised by its enhanced B-cell depletion capability compared with rituximab (RTX), obinutuzumab has demonstrated promising efficacy in the treatment of membranous nephropathy. OBJECTIVE: This study aimed to investigate the efficacy and safety of obinutuzumab in treating various subtypes of PMN. METHODS: A total of 94 PMN patients with NS were enrolled in this study. Based on their treatment history before receiving obinutuzumab, the patients were categorised into the Initial therapy group (group A, n=32), the Refractory group (group B, n=32), and the Remedial therapy group (group C, n=30). The efficacy and safety of obinutuzumab treatment after a 24-month follow-up period were observed and analysed in each group. The primary endpoint was the clinical remission rate (complete remission + partial remission) at 24 months, and the secondary endpoints were treatment safety and the incidence of treatment-emergent adverse events. RESULTS: Following 24 months of obinutuzumab therapy, 95.74% (90/94) of the PMN patients achieved clinical remission, with 28.72% (27/94) reaching complete remission (CR) and 67.02% (63/94) achieving partial remission (PR). The Initial therapy group (group A) achieved a 100% (32/32) clinical remission rate: 37.5% (12/32) attained CR, and 62.5% (20/32) attained PR. The Refractory group (group B) achieved a 96.88% (31/32) clinical remission rate: 25% (8/32) attained CR, and 71.88% (23/32) attained PR. The Remedial therapy group (group C) achieved a 90% (27/30) clinical remission rate: 23.33% (7/30) attained CR, and 66.67% (20/30) attained PR. All 63 anti-PLA2R antibody-positive (>20 U/mL) patients and 16 anti-PLA2R antibody negativity but no immunological remission (2-20 U/mL) patients demonstrated declining antibody levels following obinutuzumab therapy, and 68.4% (54/79) attained complete immunological remission (<2 U/mL). CONCLUSION: Obinutuzumab demonstrates high clinical remission rates and acceptable safety in PMN patients, with good efficacy even in refractory and RTX-resistant patients.