anti-GBM Disease Research Articles

Diffuse Alveolar Hemorrhage (DAH) Secondary to Influenza B in a Kidney Transplant Recipient with Anti-glomerular Basement Membrane (Anti-GBM) Disease

Diffuse Alveolar Hemorrhage (DAH) Secondary to Influenza B in a Kidney Transplant Recipient with Anti-glomerular Basement Membrane (Anti-GBM) Disease

Rituximab to the Rescue in Refractory Anti-GBM Disease

Rituximab to the Rescue in Refractory Anti-GBM Disease

A Rare Case of Anti-GBM Disease Complicated by Thrombotic Microangiopathy

A Rare Case of Anti-GBM Disease Complicated by Thrombotic Microangiopathy

A Rare Case of Atypical IgA-Mediated Anti-GBM Disease with ANCA-Associated Glomerulonephritis

A Rare Case of Atypical IgA-Mediated Anti-GBM Disease with ANCA-Associated Glomerulonephritis

Etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children: a systematic review.

Crescentic glomerulonephritis, if not managed promptly, is associated with unsatisfactory outcomes. There are limited studies reporting the outcomes of crescentic glomerulonephritis in children. This systematic review is aimed at synthesizing the data on etiology, clinical profile, and outcomes of crescentic glomerulonephritis in children. We performed a literature search using PubMed, Embase, and Web of Science from inception to January 2024 without language or geographic restrictions. Cohort and cross-sectional studies with at least 10 participants reporting etiology, clinical features, and outcomes on crescentic glomerulonephritis in children were considered eligible. Children aged less than 18years with crescentic glomerulonephritis. We used a tool by Hoy et al. for assessing the quality of studies. We calculated pooled estimates using random effect meta-analyses. Primary outcome was the pooled proportion of patients progressing to kidney failure. From 1706 records, we included 36 studies (1548 participants) from 16 countries. Etiology was immune-complex glomerulonephritis in 76% (95% CI 67 to 85), pauci-immune in 19% (13 to 25), and anti-GBM disease in 5% (3 to 7) of patients. Gross hematuria, oliguria, edema, and hypertension were observed in 63% (41 to 82), 57% (34 to 79), 79% (65 to 90), and 64% (49 to 77), respectively. In-hospital mortality, reported in 11 studies, was 7% (4 to 11). Progression to kidney failure and chronic kidney disease was reported in 27% (21 to 33) and 50% (29 to 71) ofpatients, respectively. Risk factors for kidney failure included oliguria, dialysis requirement at onset, estimated GFR, proportion of fibrous crescents, and pauci-immune glomerulonephritis as the underlying etiology. High heterogeneity in pooled estimates of the outcomes. Immune-complex glomerulonephritis is the most common etiology in children, with edema, hypertension, gross hematuria, and oliguria being the chief presenting manifestations. Almost one in every four patients with crescentic glomerulonephritis progressed to kidney failure. PROSPERO registration number CRD42024500515.

Atypical Anti-GBM with ANCA Vasculitis- A Rarest of the Rare Entity: Index Case from Eastern India

Anti-glomerular basement membrane (GBM) antibody glomerulonephritis is an extremely rare glomerular disease. Around 90% of the patients are positive for serum anti-GBM antibodies while up to 10% can be negative. In such patients, only a kidney biopsy can reveal the anti-GBM disease it is then labeled as an atypical anti-GBM disease. Though anti-GBM disease can be associated with Anti Neutrophil Cytoplasmic Antibodies (ANCA) positivity, it is extremely rare to find atypical anti-GBM with ANCA positivity so much so that till now there are very few such cases reported from across the world. The case presented here is one such case where the patient presented with adult-onset nephrotic syndrome features with active urinary sediments and mildly deranged renal function. Myeloperoxidase (MPO) ANCA was positive and it was considered ANCA-associated crescentic glomerulonephritis (GN) but after the renal biopsy the picture was of anti-GBM disease. She was treated with pulse methylprednisolone but her creatinine increased in the meantime and considering anti-GBM she was put on Plasma Exchange (PLEX). She received 5 sessions of PLEX after which her renal function improved. She was also planned for Rituximab which could not be given due to local infection. As there are no protocols for treating such cases because of the extremely rare nature of the presentation, this case will increase the understanding of such presentations for the clinicians. This will help to plan for building the approach for such cases.

Clinical features and prognosis of patients with anti-GBM disease combined with mesangial IgA deposition.

Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5μmol/L, IQR:270.0~702.0 vs. 515.8~1231.2μmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2μmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2μmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease.

Anti-Glomerular Basement Membrane Antibody Disease: Clinicopathologic Profile and Outcomes

Background: Anti-glomerular basement membrane antibody disease is a rare autoimmune disease caused by antibodies to α3 chain of type 4 collagen. Patients presenting with severe renal involvement requiring dialysis have poor response to treatment. Materials and Methods: We conducted a retrospective and prospective study at Institute of Nephrology, Madras Medical College, Chennai, India by analyzing the data of patients with biopsy-proven anti-GBM antibody disease treated from January 2013 to December 2019. Results: There were 2,949 kidney biopsies in the study period and 92 showed crescentic glomerulonephritis (GN). Of those, 20 patients (10 males) had anti-GBM antibody disease. Mean age was 40.75 ± 14.75 years. Rapidly progressive renal failure was the most common mode of presentation (95%); five (25%) patients had diffuse alveolar hemorrhage (DAH) and nineteen patients (95%) required dialysis at presentation. Seven patients (35%) were positive for anti-neutrophil cytoplasmic antibody (anti-myeloperoxidase in six and anti-proteinase 3 in one). Of the twelve patients (60%) who received immunosuppression (cyclophosphamide, steroids, and plasma exchange), two patients (10%) attained remission, and two patients (10%) expired due to sepsis. Crescentic GN was the predominant pathology in kidney biopsy in 19 patients (95%). Mesangial hypercellularity with deposition of IgA and C3 in mesangium was present in one patient. Conclusion: In our study, anti-GBM antibody disease accounted for 21.7% of crescentic GN. Majority of patients presented late, requiring dialysis. Patient survival was 90%, while renal survival was only 10%. One patient had co-occurrence of IgA nephropathy with anti-GBM antibody disease.

Diagnosis of membranous nephropathy with Anti-GBM glomerulonephritis: a case series report

BackgroundThe concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes.Case presentationWe present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction.ConclusionThe simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.

#1283 Rituximab in addition to plasma exchange, cyclophosphamide and steroids for treatment of anti-GBM disease

Abstract Background and Aims Anti-GBM disease is a rare antibody-mediated vasculitis, usually treated with plasma exchange (PEX), cyclophosphamide (CYC) and steroids. There are limited data regarding the use of B-cell depleting therapies such as rituximab (RTX). We investigate the use of the addition of rituximab for the treatment of Anti-GBM disease. Method Ten-year (2012-2023) single-centre retrospective cohort study of patients with anti-GBM disease treated with or without rituximab, in addition to standard care, as first-line therapy. A Cox-proportional hazards regression model incorporating age, sex, ANCA status, dialysis need at presentation, lung haemorrhage, CYC (oral or IV) and RTX treatment was used to identify disease/treatment factors associated with outcome (death, end-stage kidney disease [ESKD], infection). Results Forty-five patients are included; baseline demographics, disease characteristics, treatments and outcomes are summarised in Table 1. In the Cox regression model, only increasing age was associated with risk of death (HR 1.08 [95% CI 1.02-1.17]). Age (HR 1.04 [1.01-1.08]), female sex (HR 4.93 [1.80-4.87]), and dialysis need at presentation (HR 5.28 [1.54-17.53]) were associated with ESKD-risk. Increasing age (HR 1.04 [1.00-1.09] and ANCA positivity (HR 3.08 [1.14-8.71]) were associated with risk of infection. The addition of rituximab was not significantly associated with risk of death (HR 0.82 (0.24-2.87), ESKD (HR 1.54 [0.64-3.96]) or infection 2.06 [0.67-5.71]. Conclusion Addition of rituximab to standard treatment for anti-GBM disease was not associated with improved renal outcome or survival benefit. However, rituximab use permitted lower cumulative doses of CYC and reduction in the number of PEX, without an increased risk of infection. Rituximab may have a role as a CYC- and PEX-sparing treatment in patients with anti-GBM disease.

#2842 Increased incidence of anti-glomerular basement membrane disease in Madrid in the past two decades

Abstract Background and Aims Recently, epidemiological changes have been identified in the incidence of anti-glomerular basement membrane (GBM) in different European regions, reporting an increased incidence in population-based studies in Ireland and Denmark, possibly due to demographic changes and exposure to environmental triggers, since the evidence of spatial and temporal clustering of cases suggests that environmental factors could be playing a role in this trend. The aim of our study was to evaluate the changes in incidence of anti-GBM disease in the past two decades in two different urban areas in Madrid (North and Southwest), identify possible environmental triggers, and analyse temporal and within-area differences in presentation and outcome of the disease. Method We performed a retrospective observational study using data between 2006 and 2022 from the hospital coding databases and laboratory databases of two hospitals in Madrid covering a population of 884000 residents. We collected data from patients who were diagnosed with anti-GBM disease with confirmed positive anti-GBM antibodies and renal and/or pulmonary manifestations. We excluded patients with positive anti-GBM antibodies without clinical manifestations suggestive of the disease. Incidence was described as per 100000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. In order to detect changes in incidence, we divided the analysis into three time periods: 2006-2010, 2011-2016 and 2017-2022. We also compared the incidence before and after the onset of COVID-19 pandemic in Madrid (March 2020). Demographic data, clinical data at presentation, previous exposure to environmental factors (smoking, exposure to hydrocarbons, infections, vaccination), and treatments received and outcome was collected. Renal survival was defined as a state free from renal replacement therapy. Results During the 17-year study period, 26 cases of anti-GMN disease were identified (incidence rate 2.94 per 100000 persons); with a mean age of 52 ± 26 years at presentation, and 53.6% were females. 30.8% of patients were double-seropositive for ANCA and anti-GBM, 42.3% presented only renal involvement, 3.8% with only pulmonary involvement, and 53.8% with both renal and pulmonary involvement. At presentation, 19.2% of patients required mechanical ventilation and 65.4% required renal replacement therapy. After induction treatment, 13 patients (50%) remained on maintenance dialysis. After a median follow-up of 33 months, 46.2% patients died. Renal and patient survival after 1 year was 30.8% and 73.1% respectively. The incidence rate gradually increased from time periods 2006-2010 to 2017-2022, from 1.81 cases per 100000 persons (CI95% 0.78-3.57) to 2.83 cases per 100000 persons (CI95% 1.58-4.66) (OR 1.56, CI95%0.66-3.69, p = 0.30). We observed that the incidence rate significantly increased from 1.13 cases per 100000 persons (95% CI 0.62-1.90) before March 2020 to 4.53 cases per 100000 persons (95% CI 2.34-7.90) after the onset of the COVID-19 pandemic (OR 4, P &amp;lt; 0.001). Serum creatinine at presentation was significantly lower in cases diagnosed after COVID-19 (5.09 ± 4 vs 8.7 ± 3.9 mg/dl, p = 0.037). We found no differences within time periods in demographic data, previous exposure to environmental triggers, presence of double-seropositivity, or treatments received or patient survival after 1 year. However, we found that renal survival after 1 year has improved from 0% in 2006-2010 to 46.7% in 2017-2022 (p = 0.023) and 14.3% pre-COVID to 50% post-COVID (p = 0.049). Conclusion There is a gradual increase in the incidence rate of anti-GBM disease in our population, which has markedly increased after the COVID-19 pandemic, with a significantly lower serum creatinine at presentation with improved renal survival. We did not find any changes in the rate of exposure to known environmental triggers within time periods. These findings suggest that the rising incidence may be attributable to an increased awareness and diagnosis of anti-GBM disease, which leads to a better renal survival.

#1290 Adverse proinflammatory responses in the kidney after FGF23 administration in three murine kidney disease models

Abstract Background and Aims The hormone FGF23 is a biomarker associated with morbidity and mortality in individuals with and without kidney disease, but the role of FGF23 excess as a pathogenic factor is incompletely understood. Here, we investigated renal FGF23 signaling in kidney disease models. Method This study used three independent disease models: i) Male C57BL/6 mice (n = 16) were treated with Freud's adjuvant and nephrotoxic serum (NTS) to induce anti-glomerular basement membrane (anti-GBM) disease. ii) Female BALB/c mice (n = 8) were treated with adriamycin (doxorubicin) 10.5 mg/kg to induce focal and segmental glomerulosclerosis (FSGS). iii) Male DBA/2J mice (n = 20) were fed a diet containing adenine 0.2%. Control mice of the respective same strain and sex received vehicle injections. Mice of the anti-GBM and FSGS models and controls received intravenous injections of recombinant FGF23 1 µg or vehicle for six consecutive days (anti-GBM) or once (FSGS), with dissection 24 h after the last injection. Mice of the adenine model were dissected after 15 weeks. Following dissection, ex vivo precision-cut kidney slices (PCKS) were obtained from n = 4 mice and maintained for 24 at 37°C, 95% O2 and 5% CO2, followed by a 1 h treatment with recombinant FGF23 200 ng/ml or vehicle. Glomerular filtration rate (GFR) or renal retention parameters in serum and albuminuria were assessed. Kidneys underwent histological assessment using hematoxylin &amp; eosin or Masson's trichrome. Renal RNA was isolated for bulk RNAseq. Differential gene expression was assessed to determine the effect of FGF23 treatment in disease-free controls, in each disease model, and the interaction between FGF23 X disease effect for the anti-GBM and FSGS groups. Gene set enrichment analysis was performed with a focus on the immune system. Results Anti-GBM mice showed a 45 ± 27% GFR decline (mean ± SD) compared to baseline, whereas controls showed an GFR increase of 11 ± 36% (p &amp;lt; 0.01). Kidney histology revealed an interstitial infiltrate. The FSGS model showed elevated serum creatinine and albuminuria, and hypercellularity in some glomeruli. Mice of the adenine model showed progressively increased blood urea nitrogen concentrations starting after 2 weeks, up to a 3-fold increase at week 14. Histology revealed interstitial fibrosis and tubular atrophy. Bulk RNAseq revealed proinflammatory transcriptional signatures after FGF23 treatment in all disease models, regardless of which timepoint or model: In the anti-GBM model, Hallmark gene sets of inflammatory response, interferon-α response, interferon-β response and allograft rejection were significantly increased after 6 days of FGF23 treatment, whereas disease-free controls showed no significantly changed immune gene sets after 6 days of FGF23. In FSGS mice, none of the Hallmark gene sets were changed after 1 FGF23 injection, but top individual gene expression affected by 1 FGF23 injection were an increased proinflammatory transcription factor Cebpb and an increased DNA damage transcript Dclre1b. Finally, the PCKS of adenine model revealed no significant Hallmark gene sets, but the two genes with differential expression were a proinflammatory macrophage/fibroblast chemokine Ccl4 (increased) and an immunoglobulin heavy variable Ighv2-2 (decreased). Conclusion FGF23-driven patterns of proinflammatory gene expression were observed in three experimental models of kidney disease, both in vivo and ex vivo assessment of FGF23 signaling, thus excluding effects of FGF23 on other organs. As these findings were limited to transcriptional analyses, the present data warrant further confirmation and exploration of FGF23 as a pathogenic agent in kidney disease.

#1603 A potent protein inhibitor of HB-EGF protects kidneys from glomerular lesions in a pig model of crescentic glomerulonephritis

Abstract Background and Aims Crescentic glomerulonephritis (CGN) is a severe disease that rapidly destroys the glomerular architecture. CGN is due to immuno-inflammatory aggressions triggered by anti-neutrophil cytoplasmic autoantibody-associated vasculitides, anti-glomerular basement membrane (GBM) autoantibodies, or immune complexes deposition as occurs in systemic lupus erythematosus, IgA nephropathy or infections. Treatments are based on aggressive immunosuppression. Although required, immunosuppression doesn't directly target the deleterious glomerular response to inflammation and leads to significant morbidity. Moreover, most patients still develop chronic or end-stage kidney failure, indicating that complementary strategies are needed. We showed previously that local over-expression of the growth factor HB-EGF (Heparin-binding EGF-like growth factor) and subsequent activation of EGFR lead to dedifferentiation and proliferation of parietal epithelial cells and podocytes, leading to crescentic lesions that irreversibly obliterate the glomeruli. We aimed to evaluate the therapeutic potential of a protein inhibitor of HB-EGF in a pig model of CGN. Method We engineered a protein inhibitor of HB-EGF, DTR8, from the receptor-binding domain of diphtheria toxin, a highly selective natural ligand of HB-EGF. Twelve mutations improved solubility, led to pM affinity, and reduced immunogenicity and antigenicity. Pigs received decomplemented nephrotoxic serum (NTS) from sheep immunized against pig GBM to mimic anti-GBM antibodies disease responsible for one form of CGN. Ten pigs were treated with 0.3 mg/kg of DTR8 twice a day by intramuscular route for 20 days, and 12 pigs received vehicle only starting 6 hours after NTS. Animals were sacrificed on day 21, and blood, urine and kidneys were analyzed. Five animals that had received pre-immune sheep serum served as controls. Results Pigs developed a nephritic syndrome with high proteinuria, hypoalbuminemia, kidney failure with increased BUN and blood creatinine levels, anasarca and crescentic lesions typical of CGN along with de novo HB-EGF glomerular overexpression. The vehicle-treated group had only 24.8% of histologically normal glomeruli, while the DTR8-treated group had 57.3% of healthy glomeruli. DTR8 treatment significantly reduced the percentage of crescentic lesions (P = .0365) and preserved podocyte differentiation as assessed by the expression of nephrin that was markedly reduced in vehicle-treated animals but maintained close to normal in DTR8-treated animals (P = .0028). DTR8 administration reduced EGFR phosphorylation in glomerular cells (P = .0161), suggesting local inhibition of the HB-EGF/EGFR cascade. Lymphocyte infiltration was reduced (P = .2543). Notably, the treatment group also displayed a global reduction in interstitial fibrosis (P = .0313). Conclusion The therapeutic protein candidate DTR8 protects kidney glomeruli in a CGN model in pigs.

Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient’s kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

381 Double Trouble: Two cases of “double-seropositive” ANCA and Anti-GBM Disease

381 Double Trouble: Two cases of “double-seropositive” ANCA and Anti-GBM Disease

Short-chain fatty acids ameliorate experimental anti-glomerular basement membrane disease

BackgroundShort-chain fatty acids (SCFAs), as the link between gut microbiota and the immune system, had been reported to be protective in many autoimmune diseases by the modulation of T cell differentiation. The pathogenic role of autoreactive Th1 and Th17 cells and the protective role of Treg cells in the pathogenesis of anti-GBM disease have been fully demonstrated. Thus, the present study aimed to investigate the therapeutic effects of SCFAs in a rat model of anti-GBM disease. Materials and methodsExperimental anti-GBM disease was constructed by immunizing Wistar Kyoto rats with a nephrogenic T cell epitope α3127–148, and intervened by sodium acetate, sodium propionate, or sodium butyrate, 150 mM in the drinking water from day 0 to 42. Kidney injury was accessed by the biochemical analyzer, immunofluorescence, and immunohistochemistry. Antibody response was detected by ELISA. T cell clustering and proliferation were detected by flow cytometry. Human kidney 2 (HK2) cells were stimulated in vitro and cytokines were assessed by quantitative real-time PCR. ResultsTreatment with sodium acetate, sodium propionate, or sodium butyrate ameliorated the severity of kidney impairment in rats with anti-GBM glomerulonephritis. In the sodium butyrate-treated rats, the urinary protein, serum creatinine, and blood urea nitrogen levels were significantly lower; the percentage of crescent formation in glomeruli was significantly reduced; and the kidneys showed reduced IgG deposition, complement activation, T cell, and macrophage infiltration as well as the level of circulating antibodies against anti-α3(IV)NC1. The treatment of sodium butyrate reduced the α3127–148-specific T cell activation and increased the Treg cells differentiation and the intestinal beneficial bacteria flora. It also alleviated the damage of HK2 cells treated with inflammatory factors and complement. ConclusionTreatment with SCFAs, especially butyrate, alleviated anti-GBM nephritis in rat model, indicating its potential therapeutic effects in clinical usage.

Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group

Rationale & ObjectiveAtypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional ELISA. We characterized a series of patients with atypical anti-GBM disease. Study DesignCase series. Setting & ParticipantsPatients were identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FindingsAmong 38 potential cases, 25 were included. 14 (56%) were female and 23 (92%) had hematuria. Median [interquartile range (IQR)] serum creatinine at diagnosis was 150 [102-203] μmol/L and median [IQR] urine protein to creatinine ratio was 2.4 [1.3-5.2] g/g. 9 (36%) patients had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The nine patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at one year was 83% and did not appear to be associated with the light chain restriction. LimitationsRetrospective case series with a limited number of biopsies including electron microscopy. ConclusionsCompared to typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.

Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease

A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P< 0.001). N and serum creatinine at presentation (cut-off values 750 μmol/l and 1300 μmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C]= 0.738 and C= 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N≥10% achieved better kidney outcomes than those without RRT but N<10%. Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.

Laminin-521: a novel target for pathogenic autoantibodies in anti–glomerular basement membrane disease

Anti-glomerular basement membrane (anti-GBM) disease is typically characterized by autoimmunity against the α3 chain of type IV collagen. Rarely, circulating autoantibodies are not detected. These atypical cases follow a more indolent clinical course, and underlying mechanisms, including alternative target antigens, require investigation. In this issue of Kidney International, Kuang etal. describe a case of anti-GBM disease with autoantibodies against the GBM component laminin-521 and demonstrate that laminin-521 is pathogenic in a rat model of anti-GBM glomerulonephritis.