anti-GBM Antibodies Research Articles

Renal and overall outcomes of double-positive (ANCA and anti-GBM antibodies) patients compared to ANCA-associated vasculitis patients with severe renal involvement: A multicenter retrospective study with systematic renal pathology analysis

Objective Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement. Method This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 μmol/L), all with biopsy-proven nephropathy. Results All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 μmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients. Conclusion Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.

MO939RECURRENCE AND OUTCOME OF ANTI-GLOMERULAR BASEMENT MEMBRANE GLOMERULONEPHRITIS AFTER KIDNEY TRANSPLANTATION: A BELGIAN MULTICENTER STUDY

Abstract Background and Aims Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited case reports and registry analysis. The aim of this study was to evaluate in a large cohort of patients with detailed data collection and long follow-up the risk of recurrence of anti-GBM disease and graft loss caused by recurrence, the risk factors associated with clinical recurrence and the long-term patient and graft survival. Method Multicenter retrospective study. Inclusion criteria: patients with anti-GBM glomerulonephritis transplanted with a kidney between 1977 and 2015. Exclusion criteria: systemic vasculitis (except ANCA), lupus erythematosus and cryoglobulinemia. Clinical recurrence was defined as reappearance of signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies. Results Fifty-three patients were included. Clinical recurrence in a first kidney transplant occurred in only one patient five years after transplantation -a prevalence rate of 1.9%- in the context of cessation of immunosuppressive drugs. The graft was lost due to recurrence. Histological recurrence with linear IgG staining on kidney biopsy in the absence of histologic signs of proliferative glomerulonephritis was observed in four patients, in the context of cellular rejection. Two patients lost their kidney graft from severe acute rejection; the others fully recovered. Patient survival was 100%, 94% and 89% at 5, 10 and 15 years, respectively. Overall, death-censored first graft survival rates were 88%, 83% and 79% at 5, 10 and 15 years, respectively. Conclusion Recurrence rate of anti-GBM glomerulonephritis after transplantation is very low, and associated with graft loss. The long-term patient and graft survival rates are excellent.

MO293NEUTROPHIL-TO-LYMPHOCYTE RATIO AND OUTCOME IN CRESCENTIC GLOMERULONEPHRITIS

Abstract Background and Aims Crescent formation is a nonspecific response to severe injury to the glomerular capillary wall, which may be seen with any form of inflammatory glomerulopathy. Despite improved therapeutic interventions, patients with crescentic glomerulonephritis (CGN) still have a severe kidney prognosis and high mortality. Since neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker linked to worse outcomes in patients with malignancies, chronic kidney disease, myocardial infarction, and other clinical settings, we aimed to assess if NLR can predict kidney outcome and mortality in subjects with CGN. Method Eighty-four adults with biopsy-proven CGN between 1st Jan. 2008 and 31st Dec. 2017 [age 56 (95%CI 53 to 59) years, 50% males, eGFR 9.3 (95%CI 7.8-12.7) mL/min] were retrospectively enrolled in this single-centre study. Subjects were followed for a median of 31 (95%CI 6 to 56) months, until 31st May 2018. Seven subjects with inadequate biopsy sample and insufficient data were excluded. Demographic (age, gender), clinical and laboratory data at the time of biopsy were obtained from medical records. Kaplan-Meier method was used to evaluate kidney and patient survival. Variables related to kidney outcome were evaluated in a multivariate Cox proportional hazard (CPH) model. According to median NLR value (4.3, 95%CI 3.5 to 5.2) subjects were clustered in low NLR group (≤4.3; n=38 pts.) and high NLR group (&amp;gt;4.3; n=38 pts.). The primary endpoints were time to renal replacement therapy (RRT) initiation and all-cause mortality. Results The most common CGN subtype was pauci-immune GN (76.3%; i.e. myeloperoxidase-ANCA vasculitis - 48.7%, PR3-ANCA vasculitis - 15.8% and ANCA-negative vasculitis - 11.8%) followed by. anti-GBM antibody and immune complex related GN, with similar frequencies (11.8% each). According to kidney biopsy (KB) findings, half of the subjects had fibro-cellular crescents (55.3%), while cellular and fibrous crescents were found in 35.5% and 9.2%, respectively. Almost all subjects received corticosteroids (97.4%) and 82.9% received cyclophosphamide. Baseline eGFR was lower in the high-NLR group (8.5 vs. 11.6 mL/min, p=0.04), but no other differences in laboratory findings at baseline between the two groups were found. In bivariate analysis, NLR was negatively associated with serum albumin (rs=-0.26, p=0.02). NLR was not associated with other inflammation markers, Charlson comorbidity score, nor with the type of crescents at KB. During the follow-up period 53.9% started RRT and 19.7% died. There were no differences regarding mortality between the two groups. The mean kidney survival time was 47.6 (95%CI 33.5, 61.7) months. Kidney survival at 12, 24, 48 and 60 months were 44, 41, 38, and 33% respectively. In univariate time-dependent analysis (Figure) patients with low-NLR (68.95%CI 48 to 88 months) had better kidney survival than those with high-NLR (25, 95%CI 13 to 38 months; log rank p=0.004). Moreover, the kidney survival advantage remained (OR 1.06, 95%CI 1.002 to 1.16) after adjusting for eGFR, proteinuria, C reactive protein, immunosuppressive treatment and CGN etiology. Lower eGFR-ul was also associated with poor kidney survival (OR 0.96, 95%CI 0.88 to 0.97). Conclusion In adults with biopsy-proven crescentic glomerulonephritis and advanced kidney function decline, a higher neutrophil-to-lymphocyte ratio seems to predict worse kidney survival, but not the risk of mortality.

AB0783 “RICE AND SARDINES”: AN UNUSUAL CAUSE OF RASH AND JOINT SWELLING

Background:Systemic vasculitis presents with numerous widespread manifestations. Various diseases can masquerade as systemic vasculitis (1). It is crucial to carefully evaluate patients with unusual presentations to look for vasculitis mimics. Scurvy, a disease caused by severe and prolonged vitamin C deficiency, still occurs in industrialized countries (2). Ascorbic acid is involved in various biologic processes including the synthesis of mature collagen. Lack of ascorbic acid especially affects blood vessel integrity leading to haemorrhagic manifestations characteristic of scurvy (3).Objectives:Case report highlighting that scurvy is still prevalent in the west and may present with features resembling vasculitis.Methods:Information was obtained from the patient’s medical records.Results:A 61 year old Caucasian female presented with a 3 weeks’ history of bilateral lower limb pain, rash and swelling. She was referred to acute medicine to exclude deep vein thrombosis suspected by her general practitioner. She was previously fit and well apart from diagnosis of coeliac disease and various food intolerances. She believed her symptoms started following a recent course of Metronidazole for suspected dental infection which manifested with gum bleeding.She was found to have purpuric spots and ecchymosis bilaterally in her legs, from the toes to the groin. The left knee was swollen with evidence of hematoma around the joint.She denied fever, weight loss, night sweats, arthralgia, myalgia, rash, Raynaud’s, alopecia, mouth or genital ulcers, ear-nose-throat manifestations. She denied chest pain, difficulty in breathing or symptoms of peripheral neuropathy. There was no history of asthma, inflammatory bowel disease or uveitis. She reported occasional alcohol intake, she did not smoke cigarettes nor use recreational drugs. Examination otherwise revealed no other major abnormalities with normal vital signs.Initial differential diagnosis included platelet or coagulation disorders or vasculitis. Initial blood tests revealed normal full blood count, coagulation screen, ESR, CRP, liver and renal biochemistry.Urine dip was positive for blood but not for protein. Knee aspiration was attempted but no fluid could be aspirated. Knee x-ray was unremarkable. ANA, ANCA and anti-GBM antibody tests were negative.On further review and enquiry into her symptoms and lifestyle she admitted having a diet exclusively of “rice and sardines” for nearly 2 years. This information along with clinical features led to the suspicion of Vitamin C deficiency that was subsequently confirmed. Ascorbic acid levels were &lt;2.8micromol/l (normal range 26.1-84.6.micromol/l).Replenishment of vitamin C was followed by a rapid and sustained recovery. Detailed investigation for additional macro and micronutrient deficiencies were undertaken with referral to a dietician and to gastroenterology.Conclusion:This case illustrates scurvy can present in previously “well” individuals and should be considered as a possible differential diagnosis of vasculitic lesions in the appropriate clinical context. Detailed dietary history is invaluable.

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? CON.

Vasculitis associated with the formation of ANCA manifests in several forms defined by the extent of organ involvement (renal limited or systemic), with or without granulomatous tissue involvement, and by the presence and nature of the ANCA (antimyeloperoxidase or antiproteinase 3 and associated autoantibodies, in particular antiglomerular basement membrane [anti-GBM] autoantibodies) (1). Severe kidney disease with extensive crescentic involvement and a clinical syndrome of rapidly progressive GN is common in all forms of ANCA-associated vasculitis (AAV) (1). Diffuse alveolar hemorrhage (DAH), of varying severity, can be seen in many kinds of GN (Goodpasture syndrome) but is particularly common in AAV, with or without anti-GBM antibody (2). The therapy of AAV has greatly improved in recent years, and the use of rituximab (RTX), cyclophosphamide (CYC), or combinations of RTX and CYC plus moderate doses of steroids can effectively and safely induce a complete or partial remission in the great majority of patients (3 ⇓–5). The role of adjunctive therapy with plasmapheresis (PLEX) has been controversial, except in cases where anti-GBM autoantibody disease is found alone or concomitantly with AAV. The publication of the large Plasma Exchange and glucocorticoid dosing in treatment of anti-neutrophil cytoplasmic antibody associated vasculitis (PEXIVAS) trial in 2020 has generated much attention to this controversy (6). This debate focuses on this controversy by laying out a precise question: should PLEX be used for severe AKI and/or pulmonary hemorrhage in patients with AAV? For this debate, I will interpret “severe” as meaning the need for artificial organ support (dialysis for AKI or mechanical ventilation for DAH). I will also interpret ANCA vasculitis as meaning a positive (antimyeloperoxidase or antiproteinase 3 autoantibody in the absence of anti-GBM antibody and clinical or morphologic evidence of a vasculitis involving the kidney without or with extrarenal involvement, including DAH. …

P208 A case of double positivity

Abstract Background/Aims In the absence of renal or lung involvement, the investigation of small vessel vasculitis does not routinely include checking of anti-glomerular basement membrane (GBM) antibodies. We present a patient with an MPO-ANCA positive vasculitic neuropathy who later developed anti-GBM positive glomerulonephritis. We review the literature on patients who are “double-positive” for ANCA and GBM antibodies and speculate on the utility of routinely screening all vasculitis patients for GBM antibodies in the absence of manifestations of Goodpasture’s syndrome. Methods We describe a 70 year old female who presented feeling generally unwell with reduced mobility due to discomfort in her feet. Examination was unremarkable, except for reduced temperature and joint position sense in the feet. CRP was elevated and she was found to have a weakly positive MPO titre of 32. She was treated as an MPO-ANCA positive vasculitis and neuropathy with steroids and Mycophenolate Mofetil, with a good clinical and biochemical response. Fifteen months into her treatment, routine monitoring revealed an acute kidney injury with a creatinine of 459 umol/l from a baseline of 88. Anti GBM titres were requested for the first time as part of the renal screen. MPO antibody titres were only 9, but GBM antibody titres were markedly elevated (&amp;gt;200). Renal biopsy showed focal necrotising glomerulonephritis, in keeping with anti-GBM disease. She was treated with steroids, cyclophosphamide and plasma exchange by the renal physicians. She remains dialysis dependant. Results In our patient, GBM antibodies were only requested once she developed relevant clinical manifestations of anti-GBM disease. This in contrast to nephrology practise, where ANCA and GBM antibodies are routinely requested simultaneously in the context of nephritis. It could be speculated that if the GBM antibody status had been detected sooner, we may have altered her management and possibly improved her disease course. Anti-GBM disease and ANCA-associated vasculitis are both rare conditions. However, co-existence of the two uncommon diseases in individual patients is well-described and more than chance occurrence. A study showed that 5% of ANCA-positive cases were also positive for anti-GBM antibodies, while one-third of anti-GBM positive samples had detectable ANCA. Multiple studies have shown that low level ANCA antibodies develop months to years before onset of anti-GBM disease, as seen in our patient as well.The dominant disease phenotype in double positive patients is anti-GBM disease rather than vasculitis. It is very rare for isolated anti-GBM disease to relapse. In contrast, half of double positive patients experience disease relapse and therefore, require long-term follow-up and maintenance immunosuppression. Conclusion Awareness of this double positive phenomenon is important. Rheumatologists do not routinely check anti-GBM in all vasculitis. This case highlights the importance of doing so, especially in atypical presentation of vasculitis or in relapse and refractory disease. Disclosure S. Khalid: None. J. Li: None. S. Young Min: None.

The Clinical and Pathological Features of Children With Microscopic Polyangiitis.

Objective: The aim of this study was to explore the clinical features, pathological characteristics, and the prognosis of children with microscopic polyangiitis (MPA).Methods: Ten children with MPA that were hospitalized in our hospital were included in this study. The children's pre-diagnosis status, clinical manifestations, renal pathology, treatment, and prognosis data were analyzed retrospectively.Results: All 10 cases included female patients with a median age of 8.9 years old at the time of diagnosis. MPO-ANCA antibody was positive in all cases, combined with a positive anti-GBM antibody in two cases. Nine cases had primary AAV and one had antithyroid drug (ATD)-associated MPA (secondary to methimazole). Renal involvement was found in all 10 patients, lung impairment was present in eight cases, and anemia was present in nine patients. Renal biopsies were performed in all 10 patients. Segmental focal or global glomerular necrosis was observed in 70% of the patients (7/10). The treatment mainly included steroid use combined with Cyclophosphamide and Mycophenolate. The follow-up s of the patients revealed normal renal function in eight patients and progression to end-stage renal disease (ESRD) in two patients.Conclusions: Female predisposition and positive MPO-ANCA antibody were prominent in children with MPA. The patients' kidneys and lungs were the most frequently involved organs. Corticosteroid combined with immunosuppressive therapy was recommended for the treatment of MPA. Early diagnosis, prompt aggressive treatment, and regular follow-ups are also very important factors associated with a good prognosis.

Recurrent Nephritis and/or Pulmonary Hemorrhage in Patients with Anti-Glomerular Basement Membrane Disease with and without ANCA Positivity

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is characterized by rapidly progressive glomerular nephritis with or without pulmonary hemorrhage with disease severity correlating with antibody titer. Following treatment, relapse is rare but has been reported in the literature. The objective of this study was to assess for clinical, serologic, and histologic differences associated with disease relapse in patients with anti-GBM disease. Methods: Patients seen at our facility between 1997 and 2017 were screened for anti-GBM disease by ICD 9/10 codes. They were included if the diagnosis was confirmed by a board-certified rheumatologist or nephrologist and had positive antibodies and/or biopsy results consistent with anti-GBM disease. Relapsing disease was defined as recurrence of pulmonary or renal manifestations after achieving remission following the initial presentation. All charts were reviewed for baseline demographics, clinical manifestations, and antibody positivity and compared between groups. Results: 40 patients were confirmed as having anti-GBM disease. Mean follow-up from disease onset to the date of last follow-up was 56.2 months. 8 patients had relapsing disease and 32 patients had nonrelapsing disease. Baseline characteristics and clinical manifestations were similar between groups. Patients with relapsing disease had a high incidence of anti-neutrophilic cytoplasmic antibody (ANCA) co-positivity as compared to nonrelapsing patients (50 vs. 15.6%, respectively, p = 0.059), but this did not reach statistical significance. In patients with relapsing disease, only one had positive anti-GBM antibodies at time of relapse. Conclusions: In this study, patients with relapsing disease had a high incidence of ANCA co-positivity (50%). In patients with newly diagnosed anti-GBM disease, ANCAs should be obtained to assess for the risk of relapse and to help guide long-term follow-up and treatment.

Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention.

Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.

“Triple-positive” renal limited vasculitis presenting with rapidly progressive glomerulonephritis

Rationale: Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) in a case of glomerulonephritis is often identified as a “double-positive” disease. Interestingly, the majority of “double positive” ANCA is myeloperoxidase (MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis, suggesting an ANCA-associated kidney lesion. Proteinase 3-ANCA positive diseases are also rarely reported. Patients positive for all three antibodies, i.e., triple-positive patients, are extremely rare. Patient's Concern: A 53 year-old female presented with anasarca and oliguria of 2 months’ duration. Diagnosis: Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA, proteinase 3-ANCA, and anti-GBM antibody (triple-positive). Interventions: Intravenous high dose cyclophosphamide, oral azathioprine, intravenous methylprednisolone, and plasma exchange as per British Health Professionals in Rheumatology Guidelines. Outcomes: After one-month follow-up, anasarca and proteinuria were lessened, serum creatinine was normalized, titers of MPO-ANCA levels were decreased, and anti-GBM antibody levels were normalized. Lessons: Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.

Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disease that involves the lung and kidneys and leads to rapid glomerulonephritis progression, with or without diffuse alveolar hemorrhage, and even respiratory failure. Classic cases of anti-GBM disease are diagnosed based on the presence of the anti-GBM antibody in serum samples and kidney or lung biopsy tissue samples. However, atypical cases of anti-GBM disease are also seen in clinical practice.Case presentationWe herein report the rare case of a patient with atypical anti-GBM disease whose serum was negative for the anti-GBM antibody but positive for the myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) and another atypical ANCA. Laboratory test results showed severe renal insufficiency with a creatinine level of 385 μmol/L. Renal biopsy specimen analysis revealed 100% glomeruli with crescents; immunofluorescence showed immunoglobulin G (IgG) linearly deposited alongside the GBM. Finally, the patient was discharged successfully after treatment with plasmapheresis, methylprednisolone and prednisone.ConclusionThis patient, whose serum was negative for the anti-GBM antibody but positive for p-ANCA and another atypical ANCA, had a rare case of anti-GBM disease. Insights from this unusual case might help physicians diagnose rare forms of glomerulonephritis and treat affected patients in a timely manner.

Sequential occurrence of microscopic polyangiitis and anti-glomerular basement membrane disease in a patient with small cell lung cancer: a case report

BackgroundThe association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC).Case presentationA 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air.ConclusionsTo our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome.

Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P=.46) or VA- versus VV-ECLS (P=1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P<.001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P<.01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P=.086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P=1 and P=.94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.

Clinical and immunologic characteristics of Japanese patients with anti-glomerular basement membrane disease: case reports and literature review

BackgroundClinical studies of anti-glomerular basement membrane (GBM) disease were limited because of the low incidence. We aimed to report the characteristics, treatments, and outcomes of patients with anti-GBM disease at a tertiary reference medical center in Japan and review the literature of mortality in patients with anti-GBM disease.Case presentationCase 1 was a 72-year-old Japanese man that was referred with worsening of the serum creatinine (from 1.1 to 27.3 mg/dL). Anti-GBM disease was confirmed by renal biopsy, and treatments with oral prednisolone and plasmapheresis were initiated. Although his anti-GBM antibody decreased (from 476 to 18 units/mL) after the treatments, the patient died from lung abscess. Case 2 was a 32-year-old Japanese man that presented with fever and macroscopic hematuria. At presentation, his serum creatinine was 4.2 mg/dL, and anti-GBM antibody was 265 units/mL. Renal biopsy confirmed the diagnosis of anti-GBM disease, and intensive treatments with plasmapheresis and methyl prednisolone were started, followed by oral prednisolone. Living-donor kidney transplantation was performed because his anti-GBM antibody had remained undetectable for 1 year after diagnosis. In the main text, clinicopathological characteristics of 12 patients with anti-GBM disease at our institution were summarized.ConclusionsWe found that the 1-year survival rate of patients with anti-GBM disease was 88% in our cohort, which was comparable to previous studies. Multicenter, nationwide studies are expected to evaluate prognosis of Japanese patients with this rare entity.

Concurrent Anti–Glomerular Basement Membrane Antibody Disease and Membranous Nephropathy: A Case Series

Anti-glomerular basement membrane (GBM) disease is a rapidly progressive glomerulonephritis which, in some instances, occurs concurrently with other diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Rarely, it also occurs with membranous nephropathy (MN). We report a series of such patients, characterizing their long-term follow up. Case series. Twelve patients referred to 1 medical center between 2001 and 2019 with anti-GBM disease and MN whose clinical characteristics and course were described. Patients' ages ranged from 20 to 81 years old, and all presented with severe acute kidney injury requiring dialysis on presentation or shortly thereafter. Only 1 patient had pulmonary findings on presentation. The predominant pathology was crescentic and necrotizing glomerulonephritis with linear staining for immunoglobulin G along the GBM associated with epimembranous electron-dense immune-type deposits. All 11 patients who were tested had significant titers of anti-GBM antibodies, but only 1 of the 5 tested for phospholipase A2 receptor (PLA2R) on biopsy was positive. Eight patients received therapy with cyclophosphamide, prednisone, and plasmapheresis; 2 patients with prednisone and plasmapheresis; and 2 with rituximab-based regimens. Progression to a requirement for kidney replacement therapy occurred in all 12 patients, but 2 patients later recovered kidney function. Recurrence of anti-GBM disease did not occur for any of the patients studied. Incomplete testing for PLA2R in biopsy and serum, limited sample size, and lack of uniform treatment regimen. In this case series, the presentation of concurrent anti-GBM disease and MN was characterized by rapidly progressive glomerulonephritis and poor kidney outcomes. These findings suggest possible value from earlier diagnosis and the need for identification of more effective treatment regimens.

A Case of Seronegative Pulmonary-renal Syndrome: Diagnostic and Therapeutic Challenge

BACKGROUND: Pulmonary renal syndrome (PRS) is not a single entity but is caused by varied etiologies, including anti-neutrophil cytoplasmic antibody (ANCA), associated small vessel vasculitis (such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss vasculitis), Goodpasture’s syndrome, systemic lupus erythematosus, Henoch-Schonlein purpura, cryoglobulinemia, and rare causes such as druginduced vasculitis and subacute endocarditis.&#x0D; CASE REPORT: We report a case of a 51-year-old man who was referred to our hospital with a 2-month history of breathing difficulties, mild hemoptysis, and deteriorated renal function with a serum creatinine of 269 μmol/L. Serological testing was negative for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody, and also all cultures, including blood and urine, remained negative. In the renal biopsy, not linear deposition of IgG along the GBM and crescents at varying stages with extracapillary glomerulonephritis emphasizes the possibility of a double-seronegative pulmonary renal syndrome. Regarding therapeutic dilemmas, on the 3rd day of hospitalization, we initiated immunosuppression with cyclophosphamide and corticosteroids as well as plasma exchange (5 treatments). Under immunosuppressive therapy and plasma exchange, the patient’s status continually improved; there was no pulmonary bleeding, but the serum creatinine remained high and renal function remained in stage 4 chronic kidney disease. Four weeks later, he was hospitalized again, and we faced a new therapeutic dilemma because of the rapid relapse during immunosuppressive therapy and renal function deterioration that required hemodialysis treatment. Despite repeatedly negative results for anti-GBM and ANCA, initial immunosuppressive therapy with plasma exchange (9 treatments) was included again. The patient was discharged 30 days after admission in a stable general condition, with the maintenance immunosuppressive therapy with mycophenolate mofetil and hemodialysis 3 times/week. After 24 months, we have received information from the hemodialysis center that he is on regular hemodialysis and that he is in good condition.&#x0D; CONCLUSION: We think that in this atypical case, intensive plasma exchange and immunosuppressive therapy are crucial in the early stage and maintenance therapy is necessary for vasculitis in remission. This reported case has important clinical implications because pulmonary-renal syndrome with negative ANCAs and anti-GBM antibodies is extremely rare and no treatment recommendations have been established yet.

Double-positive Anti-glomerular Basement Membrane Disease in a Child with Crescentic Glomerulonephritis: A Case Report and Review of Literature

‘Double-positive’ with anti-glomerular basement membrane (anti-GBM) antibody and anti-neutrophil cytoplasmic antibody (ANCA) is an extremely rare cause of small vessel vasculitis in children. Studies have reported a distinct hybrid phenotype in double-positive patients which requires an aggressive treatment approach. The data on double positive children are scarce with few case reports available with varied outcomes. A case of 9-year-old girl from India who had double-positive anti-GBM disease is reported here. The patient presented with complaints of edema, oliguria, gross hematuria with rising creatine and was diagnosed as rapidly progressive glomerulonephritis (RPGN). Histological examinations of linear immunoglobulin G deposits along with glomerular capillaries were suggestive of anti-GBM disease. The anti-GBM and p-ANCA antibody titers were also high, and the aforementioned findings led to a diagnosis of ‘double-positive’ anti-GBM with RPGN. She was treated with standard plasma exchange therapy along with pulse methyl prednisolone (3 doses of 30 mg/kg/day on Days 1 to 3), oral prednisolone (1.5 mg/kg on Day 4), single intravenous injection of cyclophosphamide (500 mg/m2 on Day 5) and mycophenolate mofetil (MMF; 1000 mg/m2 on Day 6) followed by maintenance treatment with oral prednisolone (1 mg/kg/day) and MMF (800 mg/m2/day) from Day 7 onwards. Overall, the anti-GBM and p-ANCA levels declined throughout the treatment period but the patient progressed towards end stage renal disease.

Recurrent, atypical anti-glomerular basement membrane disease

Anti-glomerular basement membrane disease (GBM) (Goodpasture's disease) typically presents with acute manifestations of rapidly progressive glomerulonephritis often accompanied by lung haemorrhage. Anti-GBM disease is usually monophasic. However, atypical presentations with indolent renal involvement are being increasingly recognized. Herein we report a patient who presented with lung haemorrhage, minimal renal involvement, and negative result for serum anti-GBM antibody, while immunofluorescence examination of the renal biopsy provided the diagnosis leading to the institution right treatment with excellent response. Interestingly, he had presented 10 years earlier with lung hemorrhage, more significant renal involvement clinically and histologically, with positive serum anti-GBM antibody. The present case is intended to increase our awareness regarding the variable presentations of anti-GBM disease, such as with negative serology and recurrence of anti-GBM disease. The presentation of anti-GBM nephritis with non-proliferative, non-crescentic glomerulonephritis is also highlighted. The possible explanations for negative serum anti-GBM antibody are explored with a brief review of literature.

Clinicopathological characteristics and predictors of poor outcome in anti-glomerular basement membrane disease – a fifteen year single center experience

Introduction Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis affecting the renal and lung capillary beds. We aim to study the clinicopathological characteristics and predictors of poor outcome of this disease in our population. Materials and methods This is a 15 year retrospective, single center observational study of Indian cohort. Patients with biopsy proven anti-GBM disease were studied. Results Anti-GBM disease was found in 0.5% of the total cases. The mean age at presentation was 46.7 years. Compared to renal limited disease those with pulmonary-renal syndrome had a higher frequency of hypertension, oliguria, percentage of crescents, interstitial inflammation and glomerulosclerosis. Double positive (anti-GBM and ANCA antibodies) patients showed more of glomerulosclerosis, tubular atrophy/interstitial fibrosis (IFTA) as well as periglomerular granulomas on biopsy. Patient survival at one year was 40.4% and death censored renal survival was 9.7%. Factors affecting the dialysis dependency at presentation were oligoanuria (p = .04), creatinine levels >5.7 mg/dl (p = .003), and high mean anti-GBM titers (p = .008). Atypical cases accounted for 8.3% of these patients. Oligoanuria (HR = 5.0, p = .05), high serum creatinine (HR = 1.55, p = .05), severe glomerulosclerosis (HR = 1.09, p = .03), and IFTA (HR = 2, p = .04) were associated with poor renal outcome. Advanced age (HR = 1.92, p = .03), high serum creatinine (HR = 1.9, p = .04) and high anti-GBM titers (HR = 1.01, p = .03) were associated with poor patient survival. Conclusions Anti-GBM is a rare disease with poor prognosis and varied presentations. Patients with pulmonary-renal syndrome showed severe disease whereas double positive had more of chronic changes. The predictors of poor prognosis include advanced age, oliguria, serum anti-GBM levels, serum creatinine levels, degree of glomerulosclerosis and IFTA. Atypical anti-GBM cases should be kept in mind while evaluating renal biopsies.

Anti-Glomerular Basement Membrane Disease as a Potential Complication of COVID-19: A Case Report and Review of Literature

Since the COVID-19 outbreak has started, many reports showed that COVID-19 does not affect only the respiratory system but can alter multiple organs including kidneys. Anti-glomerular basement membrane disease (anti-GBM) is a systemic disease affecting mainly kidneys and lungs. It can sometimes be triggered by a respiratory infection such as influenza however the mechanism is not clear yet. We describe a novel case of Anti-GBM disease possibly complicating COVID-19. We report a case of a 63-year-old man who was admitted to our hospital for fever and myalgia and was found to have COVID-19. During hospitalization, he developed kidney injury along with pulmonary hemorrhage and was found to have anti-GBM antibodies. Our patient was treated as a case of Anti-GBM disease potentially triggered by COVID-19. Hence, the anti-GBM disease could be a potential complication of COVID-19.