Search

Background: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune disorder that primarily affects the kidneys and, less commonly, the lungs. The rapid progression of glomerulonephritis is a hallmark of this disease, leading to significant renal damage if not treated promptly. Early diagnosis and treatment are critical to preventing irreversible kidney injury. Case Description: We report a case of a 45-year-old male who presented with 15 days of hematuria and 2 days of breathlessness. The patient had no history of hypertension or diabetes. Clinical examination revealed pallor, high blood pressure, and fine crepitations in bilateral lower lung fields. Laboratory investigations showed elevated serum creatinine, reduced hemoglobin, and significant proteinuria. Anti-GBM antibodies were markedly elevated, and a kidney biopsy confirmed the diagnosis of crescentic glomerulonephritis with a necrotizing pattern. The patient was treated with plasmapheresis, steroids, and cyclophosphamide, along with maintenance hemodialysis. Despite the aggressive nature of the disease, early intervention helped stabilize his renal function. Conclusion: This case highlights the importance of rapid diagnosis and prompt initiation of aggressive treatment in patients with anti-GBM disease presenting as rapidly progressive glomerulonephritis. Early intervention is key to preserving renal function and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background Anti-glomerular basement membrane (anti-GBM) disease presents with rapidly progressive glomerulonephritis and alveolar hemorrhage, requiring urgent management. In this study, we analyzed the relationship between plasmapheresis strategy, immunosuppressive therapy and the prognosis of anti-GBM disease patients.Method We screened newly diagnosed anti-GBM disease patients at West China Hospital of Sichuan University from 2010 to 2021. The primary outcome was a composite endpoint of in-hospital death or dialysis dependency upon discharge.Results This study enrolled 107 anti-GBM disease patients. The use of plasmapheresis was independently associated with a reduced risk of primary outcome (OR: 0.179, 95% Cl: 0.051–0.630, p = 0.007), better 2-year (HR: 0.146; 95% CI: 0.038–0.553; p = 0.005) and 8-year patient survival (HR: 0.309; 95% CI: 0.112–0.850; p = 0.023). Restricted cubic spline regression suggested that patients with 5–10 sessions of plasmapheresis had already achieved maximum risk reduction in the primary outcome. Patients who started plasmapheresis at lower serum creatinine (42.9% vs. 96.2%, p

Anti-glomerular basement membrane (anti-GBM) disease is an aggressive small vessel vasculitis usually mediated by IgG autoantibodies. We describe the case of a 73-year-old male with rapidly progressive renal failure that was diagnosed with IgA mediated anti-GBM disease associated with circulating anti-neutrophil cytoplasm antibodies (ANCA), where the diagnosis was established on kidney biopsy by detecting linear deposition of IgA along the GBM on immunofluorescence microscopy. Despite an intensive immunosuppressive regimen with plasmapheresis, steroids and oral cyclophosphamide, the disease progressed to end-stage renal failure and the patient was started on hemodialysis. [ABSTRACT FROM AUTHOR]

Background Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpasture's disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) (ClinicalTrials.gov identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients. Methods In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data. Results Patients with a rebound (n  = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73 m2, P  = .055), and patients with dialysis at 6 months had a higher EB/EA ratio at rebound (0.8 vs 0.5, P  = .047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months. Conclusions In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide. [ABSTRACT FROM AUTHOR]

Vasculitis and HIT have different etiologies, although both involve autoimmune mechanisms. Treatment of vasculitis often requires the use of an anticoagulant such as heparin, which can lead to the development of HIT and subsequent life-threatening complications. The analysis covered patients hospitalized in the Department of Internal Medicine, Nephrology and Dialysis in the period from September 2020 to March 2023. After analyzing the data, we selected four patients in whom vasculitis treatment was complicated by HIT. These included two patients with ANCA vasculitis and two patients with anti-GBM disease. We also described similar cases reported in the literature. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition that leads to rapidly progressive glomerulonephritis, particularly uncommon in children. An 8-year-old boy was admitted to the emergency department presenting with macroscopic hematuria and oliguria. Notably, he had been hospitalized 5 weeks earlier due to a COVID-19 infection, with subsequent negative COVID-PCR results upon discharge. The systemic physical examination revealed pretibial and periorbital edema, but it was otherwise unremarkable. Importantly, there was no hypocomplementemia, and all autoantibodies tested were negative, except for anti-GBM antibodies. Over the 2-day follow-up, serum creatinine levels exhibited a steady increase from 0.63 to 6.4 mg/dL. Renal biopsy result indicated crescentic glomerulonephritis associated with anti-GBM disease. The patient responded positively to treatment with methylprednisolone, cyclophosphamide, and plasmapheresis, followed by intravenous immunoglobulin. The patient showed remarkable improvement, with the last recorded serum creatinine level at 0.57 mg/dL. Our case report suggests a potential pathogenic association between COVID-19 infection and the development of anti-GBM disease, resulting in a rapidly progressive form of crescentic glomerulonephritis in children. [ABSTRACT FROM AUTHOR]

Successful vaccination has been the decisive factor in the overall decline of SARS-CoV2 infection related morbidity and mortality. However, global effects of the COVID-19 pandemic are ongoing, with reports of glomerular disease occurring in relation to both infection and vaccination. A particular rise in anti-GBM disease has been identified. Information is still emerging regarding the optimal management of such cases. We reviewed anti-GBM antibody detection rates at our test center over the past 5 years. We followed three patients with biopsy confirmed glomerular disease temporally related to COVID-19 vaccination. Each patient proceeded to receive subsequent COVID-19 vaccination as per immunologist recommendations. Further assessment included COVID-19 antibody testing in each case. A three-fold increase in significant anti-GBM antibody results noted at our center was associated with COVID infection in 10% of cases, and COVID vaccination in 25% of cases. We demonstrated that subsequent vaccination did not appear to lead to adverse effects including relapse in our three cases of COVID-19 vaccine-associated GN. We also identified positive COVID-19 antibody levels in two out of three cases, despite immunosuppression. We report a rise in anti-GBM antibody disease incidence. Our small study suggests that COVID-19 antibody testing can help determine COVID prophylaxis requirements, and subsequent vaccination with an alternative vaccine type appears safe. [ABSTRACT FROM AUTHOR]

Abstract Background Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods. Case presentation A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria. Symptoms developed one month after an upper respiratory tract infection. Laboratory results showed acute kidney injury, and hypoalbuminemia. Immunologic examination revealed both anti-GBM and anti-PLA2R positivity. Kidney biopsy demonstrated the histological features of Goodpasture’s disease and anti-PLA2R positive membranous nephropathy. Steroid, cyclophosphamide, and plasmapheresis were commenced. Despite the combined immunosuppressive, the patient remained on renal replacement therapy. Conclusions Microbial kidney injury can trigger multiple autoimmune diseases. The simultaneous occurrence of anti-glomerular basement (anti-GBM) disease and membranous nephropathy is extremely rare. Delayed recognition leads to delayed treatment, causing worse renal and patient outcomes, as well as increased financial costs.

Background: Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods.Case Presentation: A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria. Symptoms developed one month after an upper respiratory tract infection. Laboratory results showed acute kidney injury, and hypoalbuminemia. Immunologic examination revealed both anti-GBM and anti-PLA2R positivity. Kidney biopsy demonstrated the histological features of Goodpasture's disease and anti-PLA2R positive membranous nephropathy. Steroid, cyclophosphamide, and plasmapheresis were commenced. Despite the combined immunosuppressive, the patient remained on renal replacement therapy.Conclusions: Microbial kidney injury can trigger multiple autoimmune diseases. The simultaneous occurrence of anti-glomerular basement (anti-GBM) disease and membranous nephropathy is extremely rare. Delayed recognition leads to delayed treatment, causing worse renal and patient outcomes, as well as increased financial costs. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects kidneys mainly in the form of acute kidney injury but rarely can cause glomerular disease. On a very rare occasion, SARS-CoV-2 infection can be associated with anti-neutrophil cytoplasmic antigen (ANCA)-associated vasculitis and anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). We report a case of a 59-year-old man who presented with progressive renal failure 8 weeks after contracting the viral infection, which progressed slowly to severe renal dysfunction. Renal biopsy showed crescentic glomerulonephritis (CrGN) accompanied by interrupted linear IgG deposits along the glomerular basement membrane (GBM) on immunofluorescence (IF) staining with associated mild acute tubular injury. The serology for anti-myeloperoxidase (MPO), as well as anti-GBM antibodies, was positive. He was treated with steroid and pulse intravenous cyclophosphamide, following which there was a significant improvement in the renal function and serological resolution of both the antibodies 6 months post-treatment. To the best of our knowledge, this is the first reported case of "double-antibody" positive CrGN following SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

BackgroundSeveral lines of evidence implicate that there are distinct differences between patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody double-seropositive patients (DPPs) and single-positive patients. Hence, we conducted a retrospective study from a single center in China to analyze the clinical and pathological features, and prognosis of DPPs.Methods109 patients with MPO-ANCA-associated vasculitis (MPO-AAV), 20 DPPs and 23 patients diagnosed with anti-GBM disease from a large center in China were included in this study. The ratio of patients with renal biopsy in three groups were 100%, 50% and 100%, respectively. Their clinical and pathological characteristics, and outcomes were analyzed. The intensity of immune deposits in the kidney at diagnosis was detected by immunofluorescence (IF). Furthermore, multivariate Cox hazard model analysis was used to assess the clinical and histological predictors of end-stage renal disease (ESRD) and death for DPPs.ResultsIn our study, we found that patients in the DPPs group were older than the other two groups (p = 0.007, MPO-AAV vs. DPPs; p < 0.001, DPPs vs. anti-GBM). The DPPs group had a higher value of serum creatinine (p = 0.041) and lower estimated glomerular filtration rate (eGFR) (p = 0.032) compared with MPO-AAV patients. On the contrary, the DPPs group had a lower serum creatinine (p = 0.003) compared with patients with anti-GBM group. The proportion of patients with cardiac system involvement in the DPPs group was higher than anti-GBM patients (p = 0.014). Cellular crescents could be generally observed in renal biopsy of DPPs and patients with anti-GBM glomerulonephritis. In addition, Bowman’s capsule rupture was more common in DPPs than MPO-AAV patients (p = 0.001). MPO-AAV had a better renal and overall survival outcome than DPPs (p < 0.001). There was no significant difference of renal and overall survival outcome between DPPs and patients with anti-GBM disease. The incidence of ESRD in DPPs was negatively associated with lymphocyte count (HR 0.153, 95% CI 0.027 to 0.872, p = 0.034) and eGFR (HR 0.847, 95% CI 0.726 to 0.989, p = 0.036). Elevated serum creatinine was confirmed as a risk factor of both renal (HR 1.003, 95% CI 1.000 to 1.005, p = 0.019) and patient survival in DPPs (HR1.461, 95% CI 1.050 to 2.033, p = 0.024).ConclusionIn summary, compared with anti-GBM disease, DPPs tended to involve multi-organ damage rather than limited to the kidney. It is highlighted that serologic DPPs have a worse renal and patient prognosis than MPO-AAV. Moreover, we found that the risk factors of renal survival of DPPs include low lymphocyte count, elevated serum creatinine and reduced eGFR, and serum creatinine can predict patient survival.

Successful vaccination has been the decisive factor in the overall decline of SARS-CoV2 infection related morbidity and mortality. However, global effects of the COVID-19 pandemic are ongoing, with reports of glomerular disease occurring in relation to both infection and vaccination. A particular rise in anti-GBM disease has been identified. Information is still emerging regarding the optimal management of such cases. We reviewed anti-GBM antibody detection rates at our test center over the past 5 years. We followed three patients with biopsy confirmed glomerular disease temporally related to COVID-19 vaccination. Each patient proceeded to receive subsequent COVID-19 vaccination as per immunologist recommendations. Further assessment included COVID-19 antibody testing in each case. A three-fold increase in significant anti-GBM antibody results noted at our center was associated with COVID infection in 10% of cases, and COVID vaccination in 25% of cases. We demonstrated that subsequent vaccination did not appear to lead to adverse effects including relapse in our three cases of COVID-19 vaccine-associated GN. We also identified positive COVID-19 antibody levels in two out of three cases, despite immunosuppression. We report a rise in anti-GBM antibody disease incidence. Our small study suggests that COVID-19 antibody testing can help determine COVID prophylaxis requirements, and subsequent vaccination with an alternative vaccine type appears safe.

Background: IgG and complement 3 (C3) are generally found to be deposited along the glomerular basement membrane (GBM) in human anti-GBM disease. The pathogenic role of complement activation in kidney damage of anti-GBM disease has been explored in recent years. Therefore, we investigated the relationship between serum C3 and outcomes among patients with anti-GBM disease in this study. Methods: Ninety-four anti-GBM disease patients between January 2004 and December 2020 at the National Clinical Research Center of Kidney Diseases Jinling Hospital were retrospectively analyzed, and were divided into the low C3 group and the normal C3 group according to serum C3 levels at diagnosis. Fifty-six patients had undergone renal biopsy. We analyzed the clinical manifestations, laboratory tests, kidney pathology, treatment, and outcomes between the two groups. The primary endpoint was kidney failure. Cox regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and kidney failure. The outcomes of the two groups were compared by the Kaplan–Meier curve. Results: A total of 94 patients (aged 43.6 ± 16.2; male patients, 46%) with anti-GBM disease were enrolled. There were 26 patients with low C3 levels and 68 patients with normal C3 levels. Compared with the normal C3 group, patients in the low C3 group have a higher proportion of glomerular sclerosis progressing to kidney failure. Multivariate Cox regression analysis suggested that C3 is associated with kidney outcomes in patients with anti-GBM disease (HR = 0.782, 95% CI = 0.673–0.907, p = 0.001). Smooth curve fitting of generalized additive mixed model analysis indicated that the level of C3 had a linear relationship with the changing trend of kidney failure. The Kaplan–Meier curve showed that there was a statistical difference between the two groups in terms of kidney failure (p = 0.033). Conclusion: The kidney outcomes of anti-GBM disease in the low C3 group were poorer than those in the normal C3 group. The influence of C3 on the kidney outcomes of patients with anti-GBM disease may be of clinical relevance. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. Case presentation The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. Conclusion Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

Background: Anti-glomerular basement membrane (anti-GBM) disease presents with rapidly progressive glomerulonephritis and alveolar hemorrhage, requiring urgent management. In this study, we analyzed the relationship between plasmapheresis strategy, immunosuppressive therapy and the prognosis of anti-GBM disease patients., Method: We screened newly diagnosed anti-GBM disease patients at West China Hospital of Sichuan University from 2010 to 2021. The primary outcome was a composite endpoint of in-hospital death or dialysis dependency upon discharge., Results: This study enrolled 107 anti-GBM disease patients. The use of plasmapheresis was independently associated with a reduced risk of primary outcome (OR: 0.179, 95% Cl: 0.051-0.630, p  = 0.007), better 2-year (HR: 0.146; 95% CI: 0.038-0.553; p  = 0.005) and 8-year patient survival (HR: 0.309; 95% CI: 0.112-0.850; p  = 0.023). Restricted cubic spline regression suggested that patients with 5-10 sessions of plasmapheresis had already achieved maximum risk reduction in the primary outcome. Patients who started plasmapheresis at lower serum creatinine (42.9% vs. 96.2%, p  < 0.001) or lower anti-GBM antibody levels (44.4% vs. 93.3%, p  = 0.030) had lower risk of primary outcome than those at higher levels. Use of high-dose methylprednisolone ( p  = 0.505), pulsed cyclophosphamide ( p  = 0.343) or ANCA positivity ( p  = 0.115) were not related to primary outcome in anti-GBM disease., Conclusion: Plasmapheresis was protective for both in-hospital outcome and long-term survival in anti-GBM disease. Patients who initiated plasmapheresis early had a better prognosis and might only need 5-10 plasmapheresis sessions to achieve maximal risk reduction. Use of high-dose methylprednisolone or cyclophosphamide pulses was not related to improved short- or long-term outcomes in anti-GBM disease.

Anti‐glomerular basement membrane (GBM) disease (Goodpasture disease) often presents with severe kidney failure and pulmonary hemorrhage. Anti‐GBM antibodies are pathogenic, and other autoantibodies such as laminin‐521 have been identified recently, potentially indicating a subset with a more severe disease phenotype and poor prognosis. Around 30%–40% of patients are also anti‐neutrophil cytoplasmatic antibody (ANCA)‐positive and this subset combines features of anti‐GBM disease and ANCA‐associated vasculitis, with particular impact on long‐term treatment. A combination of therapeutic plasma exchange (or immunoadsorption), cyclophosphamide, and glucocorticoids is considered standard of care management, but despite early initiation, patients with poor prognostic factors often remain dialysis dependent. Imlifidase (IdeS), capable to cleave IgG within hours, has been tested in a phase II trial. Among 15 patients, 10 with poor prognosis at baseline (eGFR <15 ml/min/1.73 m2) were dialysis independent at 6 months. Further developments are needed to refine treatment approaches in anti‐GBM disease. [ABSTRACT FROM AUTHOR]

Abstract Background A number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. ‘Double-positive’ vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate. Case presentation A 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves’ disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function. Conclusions This case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV.

Goodpasture's syndrome (GPS) is a rare small vessel vasculitis characterized by circulating antibodies directed against the glomerular and alveolar basement membrane leading to renal and pulmonary manifestations. Here, we discuss a unique case of a 30-year-old Caucasian male smoker initially presenting with hemoptysis and anemia who was found to have biopsy-proven GPS with elevated anti-glomerular basement membrane (anti-GBM) antibodies. Unfortunately, the patient failed four months of standard treatment for GPS leading to end-stage renal disease (ESRD), while uniquely developing cardiorenal syndrome (CRS) with non-ischemic cardiomyopathy resulting in systolic and diastolic heart failure (HF). Despite aggressive medical management and hemodialysis, the patient's cardiac function continued to decline and the decision was made to insert an automatic implantable cardioverter defibrillator (AICD). To our knowledge, this is the first reported case of an anti-GBM-positive GPS patient who developed dilated cardiomyopathy. The importance of this report is to illustrate the rarity of developing CRS with non-ischemic cardiomyopathy and congestive heart failure from GPS and highlight the difficulty of determining management changes beyond guideline-directed medical therapy (GDMT) in GPS to slow the progression of worsening cardiac function., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Chinniah et al.)

Introduction: Apheresis allows the fast removal of autoantibodies in anti-glomerular basement membrane (anti-GBM) disease, and in severe antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. The CINEVAS study tested whether immunoadsorption (IA) allowed a faster removal of ANCA and/or anti-GBM antibodies than plasma exchanges (PEx)., Methods: CINEVAS was a prospective multicenter study comparing IA to PEx in consecutive patients with ANCA and/or anti-GBM vasculitides. The primary objective was the reduction rate in autoantibody titers between the beginning of the first and the end of the seventh apheresis session. Secondary objectives were number of sessions needed to obtain desired reduction rates; reduction rates of total Ig levels; tolerance of sessions; and patients' outcome., Results: The results of 38 patients (16 treated with IA and 22 with PEx), and 43 autoantibodies, were analyzed. There was no difference in the reduction rates in autoantibody titers between IA and PEx over 7 sessions (respectively 98% vs. 96%, P  = 0.39). The numbers of sessions needed to obtain undetectable autoantibodies, or 50%, 75%, or 90% reductions, did not differ between techniques. Greater reduction rates of autoantibodies were observed when plasma was separated by filtration compared to centrifugation, with IA and PEx. IA allowed a greater reduction in total IgG levels, and better preservation of total IgA and IgM levels than PEx. PEx sessions required higher volumes of plasma, IA sessions higher volumes of citrate; IA sessions were longer., Conclusions: IA and PEx were comparable in ANCA or anti-GBM removal kinetics, despite a faster reduction in total IgG with IA., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Rationale & Objective: Atypical 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 enzyme-linked immunosorbent assay (ELISA). We characterized a series of patients with atypical anti-GBM disease., Study Design: Case series., Setting & Participants: Patients identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022., Findings: Among 38 potential cases, 25 were included, of whom 14 (56%) were female and 23 (92%) had hematuria. The median serum creatinine at diagnosis was 150 (IQR, 102-203) μmol/L and median urine protein-creatinine ratio (UPCR) was 2.4 (IQR, 1.3-5.2) g/g. Nine patients (36%) 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 9 patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at 1 year was 83% and did not appear to be associated with the light chain restriction., Limitations: Retrospective case series with a limited number of biopsies including electron microscopy., Conclusions: Compared with typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with an endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have a slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes., Plain-Language Summary: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized histologically by bright linear immunoglobulin staining along the GBM without diffuse crescentic glomerulonephritis or circulating anti-GBM antibodies. We report a case series of 25 atypical cases of anti-GBM nephritis in collaboration with the French Nephropathology Group. Compared with typical anti-GBM disease, we observed a slower disease progression. Patients frequently presented with heavy proteinuria and commonly had evidence of endocapillary or mesangial proliferative glomerulonephritis. About half of the patients displayed a monotypic immune staining pattern; they tended to be older, with less proteinuria, and commonly without glomerular crescents in biopsy specimens. No concomitant circulating monoclonal gammopathy was detected. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract In case of AAV with kidney involvement, physicians should explore anti‐GBM antibodies and be aware of the possible sequential development of AAV, especially with MPO‐ANCA, and anti‐GBM glomerulonephritis. This sequential disease history is associated with a poor renal outcome, highlighting the need for urgent diagnosis and management.

In case of AAV with kidney involvement, physicians should explore anti‐GBM antibodies and be aware of the possible sequential development of AAV, especially with MPO‐ANCA, and anti‐GBM glomerulonephritis. This sequential disease history is associated with a poor renal outcome, highlighting the need for urgent diagnosis and management. [ABSTRACT FROM AUTHOR]

The number of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), anti-glomerular basement membrane (GBM) disease and double-positive patients (DPPs) following the coronavirus disease 2019 (COVID-19) vaccine reported in the literature is increasing, we reviewed the reported cases of AAV, anti-GBM disease and DPPs subsequent to COVID-19 vaccination, and compared the disparities in DPPs who received the COVID-19 vaccination and those who did not. We did not observe any differences in clinical phenotype of AAV, anti-GBM disease and DPPs before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. [ABSTRACT FROM AUTHOR]

The glomerular endothelial glycocalyx is postulated to be an important modulator of permeability and inflammation. The glycocalyx consists of complex polysaccharides, the main functional constituent of which, heparan sulfate (HS), is synthesized and modified by multiple enzymes. The N-deacetylase-N-sulfotransferase (Ndst) enzymes initiate and dictate the modification process. Here we evaluated the effects of modulation of HS in the endothelial glycocalyx on albuminuria and glomerular leukocyte influx using mice deficient in endothelial and leukocyte Ndst1 (TEKCre+/Ndst1flox/flox). In these mice, glomerular expression of a specific HS domain was significantly decreased, whereas the expression of other HS domains was normal. In the endothelial glycocalyx, this specific HS structure was not associated with albuminuria or with changes in renal function. However, glomerular leukocyte influx was significantly reduced during antiglomerular basement membrane nephritis, which was associated with less glomerular injury and better renal function. In vitro decreased adhesion of wild-type and Ndst1-deficient granulocytes to Ndst1-silenced glomerular endothelial cells was found, accompanied by a decreased binding of chemokines and L-selectin. Thus, modulation of HS in the glomerular endothelial glycocalyx significantly reduced the inflammatory response in antiglomerular basement membrane nephritis.

Abstract Background Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30–60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as “atypical anti-GBM disease”, with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis. Case presentation A 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient’s hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient’s hemoptysis resolved with ganciclovir, though he became dialysis dependent. Conclusions This case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty.

Introduction: Crescentic glomerulonephritis (CrGN) characterized by the presence of crescents in most (≥50%) glomeruli on renal histology clinically presents as rapidly progressive renal failure. It can occur due to diverse etiologies with varying course and renal outcomes. We studied the prognostic significance of its classification as pauci-immune, anti-GBM, and immune-complex mediated CrGN. Materials and Methods: Renal biopsies diagnosed as CrGN over 9 years were included. Clinical, biochemical, serological, and histological features of various classes of CrGN were correlated with renal outcome. Results: 215 biopsies were diagnosed as CrGN during this period. A majority (63%) were immune-complex mediated while 32% were pauci-immune, followed by anti-GBM disease (5%). 85.5% of pauci-immune CrGN were ANCA associated. The levels of proteinuria and serum creatinine were significantly higher in anti-GBM CrGN as compared to the other two classes. The various histological features including Bowman's capsule rupture, peri-glomerular granulomatous reaction, fibrinoid necrosis, and vasculitis were more common in anti-GBM disease and pauci-immune CrGN. The median renal survival was 6.3, 5.3, 2.1 months in immune-complex mediated, pauci-immune, and anti-GBM CrGN, respectively. Conclusion: Immune-complex mediated is the commonest etiology of CrGN in India. Anti-GBM disease has the worst prognosis followed by pauci-immune and immune-complex mediated CrGN. Raised serum creatinine levels (>5mg%) and the degree of glomerulosclerosis at diagnosis were predictors of poor renal survival. High index of suspicion and prompt diagnosis can improve the outcome in these patients. [ABSTRACT FROM AUTHOR]

Background: Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection.Case Presentation: The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome.Conclusion: Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease. [ABSTRACT FROM AUTHOR]

Anti‐glomerular basement membrane (GBM) disease causes rapidly progressive glomerulonephritis and end‐stage kidney disease (ESKD). Studies of post‐transplant outcomes in patients with ESKD due to anti‐GBM disease in the United States are lacking. To better characterize outcomes of transplant recipients with a history of anti‐GBM disease, we examined patient survival and graft survival among recipients with anti‐GBM disease compared with IgA nephropathy at a single center in the United States. We analyzed patient survival, graft survival, disease recurrence, and malignancy rates for kidney transplant recipients with ESKD due to biopsy‐proven anti‐GBM disease who underwent kidney transplantation at our center between 1994 and 2015. 26 patients with biopsy‐proven anti‐GBM disease and 314 patients with IgAN underwent kidney transplantation from 1994 to 2015. The incidence of graft loss was 6.2 per 100 person‐years for anti‐GBM disease, which was similar to IgAN (4.08 per 100 person‐years, p =.09). Patient mortality for anti‐GBM was 0.03 per 100 person‐years, similar to IgAN (0.02 per 100 person‐years, p =.12). Disease recurrence occurred in one of the 26 anti‐GBM patients. Four out of 26 patients (15%) developed malignancy, most commonly skin cancer. Long‐term graft and patient survival for patients with ESKD due to anti‐GBM was similar to IgAN after kidney transplantation. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane disease is a small-vessel vasculitis involving the kidneys (∼90%) and the lungs (∼60%). Antibodies against the glomerular basement membrane are directly pathogenic in anti-glomerular basement membrane disease; however, recent research has highlighted the critical role of T cells. Novel autoantigens within the glomerular basement membrane are also now recognized. Atypical forms of the disease are reported along with preceding triggers, such as immune checkpoint inhibitors, immunomodulatory drugs, and vaccines. Kidney outcomes in anti-glomerular basement membrane disease remain poor despite significant improvement in patient survival in the last 2 to 3 decades. Treatment typically relies on combined plasmapheresis with intensive immunosuppression. Dialysis dependency at presentation is a dominant predictor of kidney outcome. Histologically, a low (<10%) percentage of normal glomeruli, 100% crescents, together with dialysis dependency at presentation, is associated with poor kidney outcomes. In such cases, an individualized approach weighing the risks and benefits of treatment is recommended. There is a need for better ways to stop the toxic inflammatory activity associated with this disease. In this narrative review, we discuss recent updates on the pathogenesis and management of anti-glomerular basement membrane disease relevant to patients of all ages., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Atypical cases of anti-glomerular basement membrane (GBM) disease had absent circulating antibodies but linear IgG deposits along GBM in the kidneys. Herein, we reported the clinical-pathological features and outcome of these rare cases.Methods: Linear IgG deposit along GBM were examined by immunofluorescence on renal specimens, with exclusion of diabetic kidney disease. Circulating anti-GBM antibodies were tested by commercial ELISA assay. Clinical, pathological and follow-up data were retrospectively analyzed.Results: From 2013 to 2018, a total of 60 patients were diagnosed as atypical anti-GBM disease. They had a male predominance, with an average age of 51.7 ± 15.6 years. Three (5.0%) patients had alveolar hemorrhage. Forty five percent of them presented with acute kidney disease. All patients had linear IgG deposit along GBM, some in addition on tubular basement membrane and/or Bowmans' capsules. C3 deposition was found in 65.0% of the patients. 41.7% (25/60) of the patients showed crescent formation and the percentage of crescent was (34.7 ± 23.5)% in those patients. They had higher prevalence of hematuria and C3 deposit, higher levels of serum creatinine, worse renal and patient survival than those without crescent (P < 0.05). During the follow-up of 35.7 ± 21.4 months, 14 (23.3%) patients progressed to ESRD. The serum creatinine on diagnosis [per 200 μmol/L increase, HR (95% CI): 2.663 (1.372, 5.172), P = 0.004], serum C3 [per 0.1 g/L increase, HR (95% CI): 0.689(0.483, 0.984), P = 0.040] and the intensity of kidney C3 staining [per 1+ increase, HR (95% CI): 2.770 (1.115, 6.877), P = 0.028] were independent predictive factors for kidney outcome. Nine (15.0%) patients died of all causes.Conclusions: Atypical anti-GBM disease manifested milder kidney injury and scarce pulmonary hemorrhage compared to the classical cases. Though heterogeneous, a substantial number of the patients had complement activation and crescent formation. Patients having crescents presented with more severe clinical course and worse outcomes. The poor kidney and patient prognosis emphasize prompt interventions from physicians. The immunosuppressive intervention was not associated with kidney or patient outcome. Further studies are needed to address the optimal therapeutic regimen.

Goodpasture’s disease (anti-GBM disease) is a rare small vessels vasculitis characterized by the presence of autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane. Common feature of anti-GBM disease is a combination of rapidly progressive glomerulonephritis and alveolar hemorrhage (pulmonary-renal syndrome). We present a case of atypical disease course in a young male patient who developed alveolar hemorrhage without renal failure. The only symptom of renal involvement was isolated hematuria. Plasmapheresis combined with immunosuppression (cyclophosphamide and corticosteroids) was effective. We present a review of state-of-art data on the pathogenesis and disease course of anti-GBM disease.

Background: Atypical cases of anti-glomerular basement membrane (GBM) disease had absent circulating antibodies but linear IgG deposits along GBM in the kidneys. Herein, we reported the clinical-pathological features and outcome of these rare cases. Methods: Linear IgG deposit along GBM were examined by immunofluorescence on renal specimens, with exclusion of diabetic kidney disease. Circulating anti-GBM antibodies were tested by commercial ELISA assay. Clinical, pathological and follow-up data were retrospectively analyzed. Results: From 2013 to 2018, a total of 60 patients were diagnosed as atypical anti-GBM disease. They had a male predominance, with an average age of 51.7 ± 15.6 years. Three (5.0%) patients had alveolar hemorrhage. Forty five percent of them presented with acute kidney disease. All patients had linear IgG deposit along GBM, some in addition on tubular basement membrane and/or Bowmans' capsules. C3 deposition was found in 65.0% of the patients. 41.7% (25/60) of the patients showed crescent formation and the percentage of crescent was (34.7 ± 23.5)% in those patients. They had higher prevalence of hematuria and C3 deposit, higher levels of serum creatinine, worse renal and patient survival than those without crescent (P < 0.05). During the follow-up of 35.7 ± 21.4 months, 14 (23.3%) patients progressed to ESRD. The serum creatinine on diagnosis [per 200 μmol/L increase, HR (95% CI): 2.663 (1.372, 5.172), P = 0.004], serum C3 [per 0.1 g/L increase, HR (95% CI): 0.689(0.483, 0.984), P = 0.040] and the intensity of kidney C3 staining [per 1+ increase, HR (95% CI): 2.770 (1.115, 6.877), P = 0.028] were independent predictive factors for kidney outcome. Nine (15.0%) patients died of all causes. Conclusions: Atypical anti-GBM disease manifested milder kidney injury and scarce pulmonary hemorrhage compared to the classical cases. Though heterogeneous, a substantial number of the patients had complement activation and crescent formation. Patients having crescents presented with more severe clinical course and worse outcomes. The poor kidney and patient prognosis emphasize prompt interventions from physicians. The immunosuppressive intervention was not associated with kidney or patient outcome. Further studies are needed to address the optimal therapeutic regimen. [ABSTRACT FROM AUTHOR]

Background: A number of disease processes can culminate in rapidly progressive glomerulonephritis, including pauci-immune focal segmental necrotising glomerulonephritis, usually seen with positive serum antineutrophil cytoplasmic antibodies (ANCA). Propylthiouracil (PTU) has been associated with drug-induced ANCA-associated vasculitis (AAV), with antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) present individually and together having been recognised. 'Double-positive' vasculitis with ANCA and anti-glomerular basement membrane (GBM) antibodies has also been reported in association with PTU treatment. We present a case of PTU-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate.Case Presentation: A 51-year-old man presented 2 weeks after re-commencing propylthiouracil (PTU) treatment for Graves' disease, with a severe acute kidney injury and haemato-proteinuria. He demonstrated positive titres for autoantibodies to PR3 (76.9 IU/mL), MPO (28.8 IU/mL) and GBM (94 IU/mL). Renal biopsy demonstrated numerous glomerular crescents, widespread IgG4-positive lymphoplasmacytic infiltrate and mesangial positivity for IgA. PTU was stopped and he was treated with steroids, plasma exchange and cyclophosphamide with sustained improvement in his renal function.Conclusions: This case of drug-induced AAV presented a unique and intriguing collection of serological and histological features. We propose that the PTU-induced AAV resulted in epiphenomena of anti-GBM antibody production and an IgG4-cell-rich tubulointerstitial infiltrate. It is uncertain whether the mesangial IgA deposition preceded or resulted from the AAV. [ABSTRACT FROM AUTHOR]

Two immune complex vasculitides, IgA vasculitis (IgAV) and anti-GBM disease, represent polar extremes with regard to our understanding of disease pathogenesis, standardized management protocols and outcomes. This report compares our current approach to these uncommon entities in adults. Both diseases demonstrate degrees of small vessel necrosis and glomerular crescent formation. IgAV has an antibody response directed against unknown antigens, is often treated conservatively and has poorly studied long term renal outcomes. By contrast, anti-GBM disease presents with rapidly progressive glomerulonephritis and often results in end stage renal failure, despite intensive immunosuppression. Rarely, some cases of anti-GBM disease may be IgA predominant and bind other α-chains present in the GBM, but their clinical course is as for other anti-GBM disease patients but not IgAV, suggesting that the antigenic target rather than the antibody subclass is the critical factor in determining disease outcome. However, both conditions are associated with increased mortality in adults and result in significant chronic kidney disease and hypertension. [ABSTRACT FROM AUTHOR]

La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) ou syndrome de Goodpasture est une vascularite des petits vaisseaux. Il s'agit d'une maladie auto-immune médiée par des auto-anticorps dirigés sélectivement contre la membrane basale glomérulaire et alvéolaire, entraînant un syndrome pneumo-rénal. Il s'agit d'une maladie rare, monophasique et sévère, associant une glomérulonéphrite rapidement progressive et parfois une hémorragie alvéolaire, réalisant un syndrome pneumo-rénal. On note la présence d'anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) dans 20 à 60 % des cas. La prise en charge doit être précoce et combine des échanges plasmatiques, une corticothérapie systémique et un traitement immunosuppresseur par cyclophosphamide. L'objectif de cette mise au point est : 1) de décrire les caractéristiques physiopathologiques, cliniques et histologiques de la maladie ; 2) de caractériser les patients double-positifs anticorps anti-MBG/ANCA ; 3) de préciser les facteurs pronostiques de survie rénale et globale, et 4) de faire le point sur la prise en charge thérapeutique de cette affection. Anti-glomerular basement membrane (anti-GBM) disease or Goodpasture's syndrome is a small vessel vasculitis affecting the capillary beds of kidneys and lungs. It is an autoimmune disease mediated by autoantibodies targeting the glomerular and alveolar basement membranes, leading to pneumorenal syndrome. It is a rare, monophasic and severe disease, associating rapidly progressive glomerulonephritis and alveolar hemorrhage. The presence of antineutrophil cytoplasmic antibodies (ANCA) is reported in 20 to 60% of cases. Management should be prompt and combine plasma exchange with systemic corticosteroids and immunosuppressive therapy by cyclophosphamide. The objective of this review is: 1) to describe the pathogenesis, clinical and histological features of the disease; 2) to characterize double-positive anti-GBM/ANCA patients; 3) to highlight the prognostic factors of renal and global survival, and 4) to focus on the treatment of anti-GBM disease. [ABSTRACT FROM AUTHOR]

Short-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. Experimental anti-GBM disease was constructed by immunizing Wistar Kyoto rats with a nephrogenic T cell epitope α3 127–148 , 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. Treatment 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 α3 127–148 -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. Treatment with SCFAs, especially butyrate, alleviated anti-GBM nephritis in rat model, indicating its potential therapeutic effects in clinical usage. [ABSTRACT FROM AUTHOR]

Abstract Background We report a previously unrecognized and unreported case of a patient with anti-glomerular basement membrane glomerulonephritis following nintedanib, an orally active small molecule tyrosine kinase inhibitor. Case presentation A 59-year-old Caucasian woman with a history of idiopathic pulmonary fibrosis presented with severe acute kidney injury (creatinine 285 umol/L) secondary to anti-glomerular basement membrane glomerulonephritis disease 4 months after commencement of nintedanib. She had hematuria with red blood cell casts, nephrotic range proteinuria (3.5g/24 hours) and significantly elevated anti-glomerular basement membrane glomerulonephritis titers at 860 chemiluminescent units. A kidney biopsy confirmed severe crescentic glomerulonephritis with linear immunoglobulin G deposition in glomerular basement membrane. Despite the commencement of treatment with plasma exchange and cyclophosphamide, she remained dialysis dependent. Nintedanib was discontinued. Conclusions Onset of acute anti-glomerular basement membrane glomerulonephritis was found to be associated with recent nintedanib use suggesting that nintedanib may be a potential trigger for anti-glomerular basement membrane glomerulonephritis. This case highlights the importance of close monitoring of patients receiving new targeted therapies. Management of novel targeted agents in patients receiving dialysis is challenging because of the scarcity of specific data.

Background: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpasture's disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) (ClinicalTrials.gov identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients., Methods: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data., Results: Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73 m2, P = .055), and patients with dialysis at 6 months had a higher EB/EA ratio at rebound (0.8 vs 0.5, P = .047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months., Conclusions: In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Most patients with anti-glomerular basement membrane (anti-GBM) disease present with rapidly progressive glomerulonephritis with or without pulmonary haemorrhage; however, there are several variants and vigilance is necessary to make a correct diagnosis. Such variants include overlap with anti-neutrophil cytoplasm antibodies-associated vasculitis and membranous nephropathy as well as anti-GBM occurring de novo after renal transplantation. Moreover, patients can present with isolated pulmonary haemorrhage as well as with negative tests for circulating anti-GBM. Virtually all patients with anti-GBM disease have autoantibodies that react with two discrete epitopes on the α3 chain of type IV collagen. Recent evidence suggests that healthy persons have low-affinity natural antibodies reacting with the same epitopes, but most people are protected from developing disease-causing high-affinity autoantibodies by human leukocyte antigen-dependent regulatory T-cells (Tregs). The α3 chain-derived peptides presented by the HLA-DR15 antigen lack the ability to promote the development of such Tregs. The detection of anti-GBM in circulation using the rapid assay test has led to early diagnosis and improved prognosis. However, our present tools to curb the inflammation and to eliminate the assaulting antibodies are insufficient. Only about one-third of all patients survive with functioning native kidneys. More effective therapies need to be developed; agents that inhibit neutrophil recruitment, deplete B cells and cleave immunoglobulin G (IgG) in vivo may become new weapons in the arsenal to combat anti-GBM disease. [ABSTRACT FROM AUTHOR]

Abstract The major epitopes recognized by autoantibodies in anti-glomerular basement membrane (GBM) disease are found in the α3-subunit non-collagenous domain of type IV collagen [α3(IV)NC1], which is present in the glomerular and alveolar basement membranes. These epitopes are structurally cryptic, owing to the hexamer formation of the non-collagenous domain of α3, α4, and α5 subunits and are expressed by the dissociation of the hexamer. Anti-GBM disease usually manifests as a single attack (SA), and we rarely see patients who repeatedly relapse. We recently treated a patient with anti-GBM disease who exhibited repeated relapse (RR). Here, we conducted immunohistochemistry of formalin-fixed paraffin-embedded normal kidney sections and immunoblotting using recombinant human α3(IV)NC1 to compare the epitopes recognized by anti-GBM antibodies in the RR patient and SA patients. Although a clear staining of GBM especially in the connecting basement membrane of Bowman's capsule was observed when IgGs of SA patients were used as primary antibodies, such staining was not obtained when IgG of the RR patient was employed. In immunoblotting of α3(IV)NC1 using the IgG of the RR patient as a primary antibody, an 18-kDa band was detected besides the 56.8-kDa band corresponding to the whole-size α3(IV)NC1. Whereas the 56.8-kDa band disappeared after digestion of the recombinant α3(IV)NC1 by protease, the 18-kDa band remained. Furthermore, the 18-kDa band was not detected by a commercially available anti-α3(IV)NC1 monoclonal antibody. These findings suggest that the IgG of the RR patient recognizes the epitope distinct from that recognized by the anti-α3(IV)NC1 monoclonal antibody. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncollagenous domain of the α3-chain of type IV collagen [α3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3)+ regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here, we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with α3(IV)NC1 induced the formation of α3(IV)NC1- specific T cells and antibodies and, after 8 –10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of α3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion, our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established. [ABSTRACT FROM AUTHOR]

Background: Anti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30-60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as "atypical anti-GBM disease", with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis.Case Presentation: A 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient's hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient's hemoptysis resolved with ganciclovir, though he became dialysis dependent.Conclusions: This case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty. [ABSTRACT FROM AUTHOR]

Background: Renal failure in pregnancy is usually due to acute kidney injury and very uncommonly due to rapidly progressing glomerulonephritis (RPGN). We describe here a case of RPGN in the first trimester of pregnancy. Case Presentation: A 26 years old female patient in first trimester of pregnancy presented with RPGN. Investigations revealed dual serological positivity of anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM). The biopsy showed crescentic glomerulonephritis with linear with IgG deposition on GBM as well as mesangial IgA deposition. Despite aggressive therapy with cyclophosphamide and plasma exchange she continued to be dialysis dependent and developed end-stage renal disease. Conclusions: RPGN is an uncommon cause of renal failure in pregnancy. While the dual ANCA and anti-GBM are common in RPGN and this concurrent occurrence is wellknown, however, the association of ANCA and IgA nephropathy has been described rather uncommonly. This rare case has positivity of all three in pregnancy.