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.

Coexistence of anti-glomerular basement membrane disease and IgA nephropathy: an illustrative case and comprehensive literature review.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored.

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.

An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Antiglomerular basement membrane antibody type rapidly progressive glomerulonephritis with seizures: Two cases and literature review.

BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is clinically manifestations as a rapidly progressive renal failure and pathologically as crescentic and necrotizing lesions with infiltration of inflammatory cells in the glomeruli. Uremic encephalopathy (UE) usually develops in patients who are suffering from acute or chronic renal failure. OBJECTIVE: The purpose of this article is to provide reference for clinical diagnosis and treatment of renal disease complicated with seizures. Patients Two cases of anti-glomerular basement membrane type rapidly progressive glomerulonephritis complicated with seizures were reported. MATERIALS & METHODS: In case 1, a 40-year-old woman was hospitalized for the treatment of nausea, anorexia, and fever. On admission, she presented with elevated serum inflammatory indicators, moderate anemia, and advanced acute kidney injury requiring hemodialysis. Her anti-glomerular basement membrane (GBM) antibody in serum and renal tissues was found to be extremely high. She was finally diagnosed with anti-GBM disease. She was treated with a combination of corticosteroid pulse therapy, oral cyclophosphamide and prednisolone, and plasma exchange, while continued to require maintenance hemodialysis for end-stage kidney disease. During treatment, she suddenly suffered blindness, seizure, and consciousness disturbance. She was diagnosed as posterior reversible leukoencephalopathy syndrome by magnetic resonance imaging (MRI). The posterior reversible leukoencephalopathy syndrome subsided quickly after control of her hypertension and reinforcement of immunosuppressive treatment. In case 2, the patient also developed epileptic symptoms on the basis of GBM disease, and was given treatment similar to that of Case 1, so that the epileptic symptoms were controlled. RESULT: Reversible posterior leukoencephalopathy syndrome, especially when accompanied by cerebral hemorrhage, may lead to irreversible and lethal neurological abnormalities, and nephrologists should, therefore, be aware of the potential risk of reversible posterior leukoencephalopathy syndrome in patients with anti-GBM disease. We can discuss the current two cases in the light of the previous literature.

Anti-Glomerular Basement Membrane Disease in a 10-year-old Child: A Case Report.

Anti-glomerular basement membrane disease is an extremely uncommon entity in children. It has an incidence of 0.5 to 1 per million per year in adults and is even more uncommon in children. It occurs due to autoantibody against glomerular basement membrane collagen and is characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. As the literature on anti-glomerular basement membrane disease is limited from our part of the world, it is important to consider it as the rare cause of rapidly progressive glomerulonephritis as early intervention improves prognosis. We report a case of a 10-year-old male who initially presented with glomerulonephritis and later was diagnosed with anti-glomerular basement membrane disease. Keywords: basement membrane; case reports; glomerulonephritis; kidney.

Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease.

Background and objectives: Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease. Methods: We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival. Results: Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26-64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298-977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr). Conclusion: In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

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.

[Anti-MBG crescentic glomerulonephritis with negative immunofluorescence: case report and literature review].

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rapidly progressive glomerulonephritis characterized by (i) positivity to anti-GBM in serum reacting with a specific antigen present in type IV collagen at both the glomerular and alveolar levels (ii) presence of crescent on light microscopy and positivity to linear deposits of IgG and C3 on immunofluorescence. In the classic variant, the clinic is that of a nephro-pneumological syndrome but there are variants. Rarely, the glomerular damage is pauci-immune. We describe a case of a variant in which there is anti-MBG positivity in serum but negative immunofluorescence and offer a review of the literature and potential treatments.

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.

Rituximab for the Treatment of Anti-glomerular Basement Membrane Disease with Isolated Diffuse Alveolar Hemorrhage.

Anti-glomerular basement membrane (GBM) disease with isolated diffuse alveolar hemorrhage (DAH) is rare. We herein report a 91-year-old man admitted with hypoxia and diagnosed with anti-GBM disease with DAH based on positive bronchoalveolar lavage and serum antibody test results. There was no renal involvement. Although remission was achieved using glucocorticoids and plasmapheresis, the patient experienced DAH relapse one week after the last plasmapheresis. Rituximab 375 mg/m2 was administered 4 times weekly; thereafter, DAH relapse was not observed, and the glucocorticoid dosage was tapered. Rituximab was thus effective in treating anti-GBM disease with isolated DAH in an extremely elderly patient.

Anti-glomerular basement membrane diseases and thrombotic microangiopathy treated with rituximab.

A 68-year-old male patient presented with a 2-week history of malaise and anuria. Renal replacement therapy with haemodialysis was begun for acute kidney injury. His anti-glomerular basement membrane (anti-GBM) antibody titre was 3060 U/ml. Based on this finding, anti-GBM disease was diagnosed. Plasmapheresis and high-dose glucocorticoid therapy were begun, but his haemolytic anaemia and thrombocytopenia progressed. A disintegrin and metalloprotease with thrombospondin type 1 motif, 13 (ADAMTS-13) activity decreased to 33%, but no inhibitor was detected. Secondary thrombotic microangiopathy was suspected, and rituximab therapy was begun. The addition of rituximab is thought to have further reduced the anti-GBM antibodies, prevented recurrence, stabilised the platelet count, and facilitated the patient's withdrawal from plasmapheresis and glucocorticoid therapy. Rituximab may be a viable therapeutic option for anti-GBM diseases complicated with thrombotic microangiopathy.

Anti-glomerular basement membrane disease developing 3 years after the development of Sweet syndrome and 1 year after the development of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3 years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1 year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.

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.

Anti-glomerular basement membrane disease with rupture of the newly formed bilateral corpus luteum cysts: A case report.

RATIONALE: Anti-glomerular basement membrane (anti-GBM) disease during gestation is sparse and even rarer when combined with bilateral large corpus luteum cysts. In this case, we report a case of anti-GBM disease in the early stage of pregnancy with ruptured newly formed bilateral large corpus luteum cysts. PATIENT CONCERNS: A 24-year-old female was initially diagnosed with anti-GBM disease. During treatment, abdominal distention and vaginal bleeding successively staged. The results of the first gynecological ultrasound and abdominal CT were negative. DIAGNOSIS: Based on the dynamic imaging change of the ovaries, the elevated human chorionic gonadotropin (hCG) and sex hormones, and the pathological findings, a diagnosis of anti-GBM disease with rupture of the newly formed bilateral corpus luteum cysts during early pregnancy was considered. INTERVENTIONS: The patient was treated with corticosteroids, plasma-exchange along with intensive hemodialysis. Then, to confirm the diagnosis, laparoscopic debulking of bilateral ovarian cysts and curettage were performed. OUTCOMES: After treatment, the anti-GBM antibody titer declined and the condition of the patient was still stable 2 months following discharge. LESSONS: As clinicians, we should be aware that even if the first imaging tests are negative, the relevant indicators should be reviewed dynamically based on the condition of the patients. Additionally, this case raised the question of whether anti-GBM disease was associated with pregnancy and giant corpus luteum cysts, which needs further investigations.

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.

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.