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

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

Goodpasture syndrome: a rare case presenting with recurrent haemoptysis.

Goodpasture syndrome is a rare autoimmune disease which affects young adults with a male preponderance and can be triggered at any point in life with a classical clinical triad of rapidly progressive glomerulonephritis, diffuse pulmonary haemorrhage and circulating anti-glomerular basement membrane antibody (anti-GBM antibody). Here we are presenting a case of a young man with hypertension in his early 20s who presented with fatigue, recurrent haemoptysis, breathlessness and decreased urine output without features of infection. He was diagnosed at an early stage of the disease with the help of clinical, serological and radiological findings. An early diagnosis with effective treatment using plasma exchange, intravenous high-dose methylprednisolone, and cyclophosphamide showed a rapid improvement in the patient's condition with an immediate decrease in anti-GBM titres and proteinuria.

Atypical form of Goodpasture's disease.

Goodpasture's disease and anti-glomerular basement membrane nephritis (anti-GBM nephritis) are rare autoimmune small vessel vasculitis predominantly affecting young men. Goodpasture's disease plays an important part in differential diagnosis of pulmonary - renal syndrome. The evidence of circulating autoantibodies, a typical histological appearance of the kidney biopsy with finding of the crescent glomerulonephritis and clinical presentation of nephritic syndrome play an important role in diagnosis. Our case report describes a case of a young male with anti-GBM nephritis that presents as rapidly progressive glomerulonephritis (RPGN) with progression to dialysis-dependent renal failure. The atypical sign of the case was development of nephrotic syndrome with volume-dependent hypertension. The case was complicated by heparin-induced thrombocytopenia. During combined immunosuppressive therapy with plasmapheresis, the condition of the patient has stabilized. However, renal function did not recover. This previously fatal disease has nowadays a very good survival rate because of immunosuppresion therapy, plasmapheresis and hemodialysis.

Immunity in the balance: Fatal disseminated adenovirus infection in a patient undergoing plasma exchange and immunosuppressive chemotherapy for anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease (formerly known as Goodpasture's syndrome) is a rare autoinflammatory condition that affects the renal and/or pulmonary capillaries. The standard therapeutic regimen for anti-GBM disease involves therapeutic plasma exchange (TPE), cyclophosphamide, and corticosteroids to rapidly remove and inhibit autoantibody production and reduce organ inflammation. Herein we report an 82-year-old female who developed anti-GBM disease but expired despite therapy, secondary to multi-organ failure in the setting of disseminated adenovirus disease. We discuss the utility and potential adverse effect of daily TPE for a protracted course (ie, 10-14 days), the recommended TPE intensity in the 2023 American Society for Apheresis guidelines, updated from every-other-day TPE in the 2019 guidelines, despite no new data. We also highlight the potential for unusual infections to occur in these patients due to the profound immunosuppression, and discuss the importance of balancing immunosuppression to treat the disease with close surveillance of any potential opportunistic infections.

Therapeutic plasma exchange for anti-glomerular basement membrane disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is treated with immunosuppressive medications and plasma exchange. However, whether plasma exchange, in addition to pulse glucocorticoid therapy, would benefit patients with anti-GBM disease with dialysis-dependent kidney failure without diffuse alveolar hemorrhage remains unclear. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients diagnosed with anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage from July 2010 to March 2020. We compared in-hospital mortality within 10 days of hospitalization between patients who received therapeutic plasma exchange in addition to pulse glucocorticoid therapy and those who received pulse glucocorticoid therapy alone. Overlap weighting based on propensity score was performed to adjust for potential confounders. RESULTS: We identified 207 eligible patients; 168 patients received therapeutic plasma exchange plus pulse glucocorticoid therapy, while 39 patients received pulse glucocorticoid therapy alone. The mean dose of therapeutic plasma exchange was 52.2 ml/kg/day of albumin and/or fresh frozen plasma. Therapeutic plasma exchange in addition to pulse glucocorticoid therapy was associated with a lower in-hospital mortality risk in the unweighted (10.7% versus 28.2%; risk difference, 17.5%; 95% confidence interval, 2.6-32.4%; P = 0.02) and weighted analyses (11.5% versus 28.4%; risk difference, 17.0%; 95% confidence interval, 1.5-32.5%; P = 0.03) than pulse glucocorticoid therapy alone. CONCLUSIONS: This retrospective cohort study using a national database suggests that therapeutic plasma exchange may improve the in-hospital prognosis of anti-GBM disease with dialysis-dependent kidney failure and without diffuse alveolar hemorrhage.

Goodpasture syndrome and anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is a rare life-threatening small vessel vasculitis that typically affects the capillaries of kidneys and lungs, with most of patients developing rapidly progressive crescentic glomerulonephritis, and 40%-60% concomitant alveolar haemorrhage. It is caused by the deposition in alveolar and glomerular basement membrane of circulating autoantibodies directed against antigens intrinsic to the basement membrane. The exact mechanism that induces the formation of autoantibodies is unknown, but probably environmental factors, infections or direct damage to kidneys and lungs may trigger the autoimmune response in genetically susceptible individuals. Initial therapy includes corticosteroids and cyclophosphamide to prevent autoantibodies production, and plasmapheresis to remove the circulating autoantibodies. Good renal outcomes may be achieved by a prompt treatment initiation. However, when patients present with severe renal failure requiring dialysis or with a high proportion of glomerular crescents at biopsy, renal outcomes are bad. Relapses are rare and when renal involvement is present, the suspect of concomitant diseases, such as ANCA-associated vasculitis and membranous nephropathy, should be raised. Imlifidase is showing promising results, which if confirmed will cause a paradigm shift in the treatment of this disease.

High-frequency plasma exchange therapy for immunocompromised, type I crescentic glomerulonephritis complicated with IgA nephropathy: A case report and literature review.

RATIONALE: Anti-glomerular basement membrane (anti-GBM) disease has been reported to coexist with other immune-mediated glomerular disorders, including antineutrophil cytoplasmic autoantibody positive glomerulonephritis and membranous glomerulopathy. It is well known that anti-GBM disease often manifests as type I crescentic glomerulonephritis on renal biopsy. However, concurrent cases of both type I crescentic glomerulonephritis and IgA nephropathy are rare. PATIENT CONCERNS: We report the case of a 40-years-old woman with microscopic hematuria, mild proteinuria and an immunocompromised status. Laboratory data revealed serum creatinine showed progressive progress, suddenly rising from the normal range to 316.2µmol/L within 4 months. The CD4 lymphocyte count was 0.274 × 109/L (reference value 0.35-1.82 × 109/L). The anti-GBM antibody titer was 192.4 IU/mL (reference range: <20 RU/mL). DIAGNOSES: Renal biopsy was performed after admission. The pathological diagnosis was type I crescentic glomerulonephritis, IgA nephropathy, and clinical anti-GBM disease. INTERVENTIONS: The patient was seriously ill on admission and progressed rapidly. Combined with poor immune function, we immediately initiated high-frequency plasma exchange (PE). In addition, to avoid rebound of antibody levels, PE was performed for 5 times. Follow-up treatment was combined with standard-dose corticosteroids and cyclophosphamide. OUTCOMES: The patient was followed up for 1 year. On the last visit, her serum creatinine decreased to 103.5µmol/L, anti-GBM antibody remained negative, and proteinuria and hematuria disappeared. LESSONS: This case illustrates that when crescentic nephritis or anti-GBM disease is combined with other immune diseases, especially when the immune function is extremely low, if the application of high-dose steroid shocks may induce fatal infections, to some extent high frequency PE has certain advantages.

An atypical anti-GBM disease complicated by idiopathic nodular glomerulosclerosis: Case report.

Both atypical anti-glomerular basement membrane (anti-GBM) disease and idiopathic nodular glomerulosclerosis are rare diseases. We report a case of a 53-year-old non-diabetic male who presented with leg edema, nephritic range proteinuria, microscopic hematuria, and decreased renal function. The renal biopsy demonstrated membranoproliferative glomerulonephritis (MPGN) pattern of glomerular injury with focal crescent and segmental nodular glomerulosclerosis. The immunofluorescence studies showed intense linear IgG (IgG1 and IgG4) deposits along the GBM but negative serology. Electron microscopy demonstrated GBM thickening and fibrillar deposition. The presence of MPGN with crescents and the linear IgG along the GBM were consistent with a diagnosis of atypical ant-GBM disease. Superimposed nodular glomerulosclerosis was considered to be idiopathic by excluding other glomerular diseases characterized by fibrillar deposition and nodular glomerulosclerosis. Both diseases were found to have a strong causative association with patient's history of long-term heavy smoking. This unusual case with combination of atypical anti-GBM disease and idiopathic nodular glomerulosclerosis, has brought great challenge for the diagnosis and also made the clinical course highly complicated. This nodular glomerulosclerosis with anti-GBM-like glomerulonephritis may represent a distinct pattern of kidney injury observed in heavy smokers.

Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients.

Background: Several 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. Methods: 109 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. Results: In 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). Conclusion: In 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.

A case report of atypical anti-glomerular basement membrane disease.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic necrotizing glomerulonephritis, with linear deposits of immunoglobulin G (IgG) in the GBM. Classic anti-GBM disease is clinically associated with rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Some patients have a better renal prognosis and milder symptoms than those with classic anti-GBM disease, which is termed atypical anti-GBM disease. CASE PRESENTATION: A 43-year-old Japanese woman was admitted to our hospital complaining of hematuria that had persisted for more than one month. Serological examination revealed negativity for anti-nuclear, anti-neutrophilic cytoplasmic, and anti-GBM antibodies. However, renal biopsy showed cellular crescents. Immunofluorescence revealed strong diffuse linear capillary loop staining for IgG. An indirect immunofluorescence antibody method was performed by applying the patient serum to normal kidney tissue to confirm the presence of autoantibodies binding to the GBM. Using this method, anti-GBM antibodies were detected. The patient was treated with high-dose steroids, cyclophosphamide, and plasma exchange. Aggressive treatment resolved proteinuria and hematuria and improved renal function. CONCLUSIONS: Renal biopsy is crucial in the diagnosis of anti-GBM disease, especially when serological tests are negative. Accurately identifying the presence of anti-GBM disease is important to initiate optimal treatment.

A unique case of anti-GBM disease with concomitant anti-PLA2R positivity.

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.

Great prognosis of concurrent anti-GBM disease and IgA nephropathy in a young woman: A case report.

RATIONALE: The causal relationship between anti-glomerular basement membrane (anti-GBM) disease and immunoglobulin A (IgA) nephropathy is still unclear and cases of concurrent anti-GBM disease and IgA nephropathy are very rare, especially with a good prognosis and long-term follow-up. Here, we report a case of concurrent anti-GBM disease and IgA nephropathy. By using corticosteroids and cyclophosphamide in combination with plasmapheresis, the patient achieved a very good prognosis with complete normalization of renal function and complete disappearance of hematuria and proteinuria at the subsequent follow-up. To our knowledge, no previous case with such a long follow-up and such a good prognosis have been reported. PATIENT CONCERNS: This case report describes a 26-year-old Chinese woman who presented with fever as the initial symptom, followed by dysmorphic hematuria, overt proteinuria and rapidly worsening renal function. Before admission, the patient received symptomatic supportive treatment such as intravenous albumin infusion, improvement of circulation, but the symptoms were not significantly improved. DIAGNOSIS: Per the results of kidney biopsy, the patient was diagnosed with crescentic glomerulonephritis and anti-GBM disease with IgA nephropathy. INTERVENTIONS: The key to obtain a good prognosis was the early application of corticosteroids and cyclophosphamide in combination with plasmapheresis to make the anti-GBM antibody turn negative quickly. OUTCOMES: After 2 weeks of therapy, the patients' anti-GBM antibody turned negative and serum creatinine improved to a normal range. After 10 months, the patient's proteinuria level reached complete remission. After 12 months, the patient's hematuria had disappeared completely. LESSONS: This case provides experience in the treatment of concurrent anti-GBM disease and IgA nephropathy and highlights the importance of early application of plasmapheresis and immunosuppressive therapy to obtain a good prognosis.

Relationship Between Serum Complement C3 Levels and Outcomes Among Patients With Anti-GBM Disease.

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.

Anti-glomerular basement membrane disease associated with thin basement membrane nephropathy: A case report.

RATIONALE: Simultaneous occurrence of anti-glomerular basement membrane (anti-GBM) disease and thin basement membrane nephropathy (TBMN), both of which invade the type IV collagen subunits, is very rare. Here, we present the case of a 20-year-old male patient diagnosed with both anti-GBM disease and TBMN upon presenting dyspnea and hemoptysis. PATIENT CONCERNS: No laboratory abnormalities, except arterial hypoxemia (PaO275.4 mmHg) and microscopic hematuria, were present. Chest computed tomography revealed bilateral infiltrations in the lower lung fields; thus, administration of empirical antibiotics was initiated. Gross hemoptysis persisted nonetheless, and bronchoscopy revealed diffuse pulmonary hemorrhage with no endobronchial lesions. Broncho-alveolar lavage excluded bacterial pneumonia, tuberculosis, and fungal infection. DIAGNOSIS: Enzyme-linked immunosorbent assay of his serum was positive for anti-GBM antibody (95.1 U/mL). Human leukocyte antigen (HLA) test was positive for both HLA-DR15/-DR04. Other than diffuse thinning of the GBM (average thickness, 220 nm), index kidney biopsy did not demonstrate any specific abnormalities such as crescent formation. INTERVENTIONS: Methylprednisolone was administered intravenously for 7 consecutive days (500 mg/day), followed by the daily dose of oral prednisolone (80 mg). Cyclophosphamide was also orally administered every day for 3 months (250 mg/day). Following 6 sessions of plasmapheresis, the anti-GBM antibody in serum became negative. OUTCOMES: There was no clinical evidence suggesting recurrence of pulmonary hemorrhage or azotemia during hospitalization and 12-month follow-up period. Twelve months after hospital discharge, oral prednisolone was discontinued. LESSONS: The patients with concurrent anti-GBM disease and TBMN will have a favorable prognosis after proper therapy. However, further research is needed to elucidate the pathogenesis and long-term outcome of the comorbidity of these 2 diseases.

Seronegative Goodpasture's syndrome associated with organising pneumonia.

Goodpasture's syndrome is a rare vasculitis associated with anti-glomerular basement membrane (anti-GBM) autoantibodies that target type IV collagen found in the basement membranes of glomeruli and alveoli. We present a case of a 79-year-old man with seronegative Goodpasture's syndrome with predominant respiratory symptoms and mild acute kidney injury that initially improved. Final diagnosis was made by immunofluorescent staining on open lung biopsy which also revealed concomitant organising pneumonia. The patient underwent treatment with corticosteroids, cyclophosphamide, haemodialysis and plasmapheresis. This was an atypical presentation wherein the patient only exhibited pulmonary symptoms early in the course of illness in the setting of negative anti-GBM antibody serum testing, which made diagnosis challenging. With this case, we emphasise that clinicians should have a high suspicion for Goodpasture's syndrome in the setting of unexplained severe pulmonary or renal disease despite negative anti-GBM antibody testing.

Anti-glomerular Basement Membrane Disease with Antiphospholipid Syndrome.

A 48-year-old woman presented with a fever, microscopic hematuria, proteinuria, and rapid deterioration of the renal function. Pulmonary alveolar hemorrhaging and a high level of anti-glomerular basement membrane (GBM) antibodies (700 IU/mL) were observed. Based on her medical history and positive findings of serum lupus anticoagulant, anti-phospholipid antibody syndrome (APS) was suspected. A renal biopsy revealed cellular crescentic glomerulonephritis with thrombosis, suggesting anti-GBM disease with catastrophic APS. The patient was treated with pulse steroid therapy, plasma exchange, hemodialysis, and intravenous cyclophosphamide pulse therapy. To our knowledge, this is the first report of a patient with anti-GBM disease and APS.

SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report.

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.

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

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Twelve patients referred to 1 medical center between 2001 and 2019 with anti-GBM disease and MN whose clinical characteristics and course were described. RESULTS: 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. LIMITATIONS: Incomplete testing for PLA2R in biopsy and serum, limited sample size, and lack of uniform treatment regimen. CONCLUSIONS: 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.

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: A Rare Case Report of Changing Clinical Phenotype and Atypicalities.

A man in his late 20s, a smoker, presented with nephrotic-range proteinuria and mild renal failure. He had no macroscopic hematuria or decreased urine output. Kidney biopsy was done which revealed a surprising diagnosis of anti-glomerular basement membrane (anti-GBM) disease. He was started on intravenous methylprednisolone, plasma exchanges, and cyclophosphamide. His anti-GBM antibody was, however, weak positive. After five sessions of plasma exchange, he was discharged with a negative anti-GBM antibody. The patient defaulted drugs and presented with rapidly progressive renal failure and hemoptysis after 1½ months. The patient was started on intravenous methylprednisolone, hemodialysis, plasma exchanges, and cyclophosphamide. Repeat biopsy after stabilization was suggestive of anti-GBM disease with fibrocellular crescents. Anti-GBM antibody was negative. Although the patient presented with an estimated glomerular filtration rate of 10 mL/min/1.73 m2 and fibrocellular crescents, the patient improved with treatment and was discharged with a serum creatinine of 2.2 mg/dL. This patient had two presentations: one with nephrotic-range proteinuria and mild renal failure, revealing anti-GBM disease on biopsy, and the second with rapidly progressing renal failure which improved with treatment. There were many atypical features in his presentation. Nonabstinence from smoking might be a triggering factor for the second episode. The pathological antibodies may be against a nonconventional epitope or poorly complement fixing, resulting in negative anti-GBM antibody and good recovery in spite of severe renal failure.