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.

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.

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

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

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.

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: Treatment outcome of cyclophosphamide vs. rituximab induction therapy regimen.

AIM: To study the clinical profile of anti-glomerular basement membrane (anti-GBM) disease and its outcome with two different treatment regimens comprising either cyclophosphamide (CYC) or rituximab (RTX). MATERIALS AND METHODS: A retrospective analysis of anti-GBM crescentic glomerulonephritis patients admitted to our hospital over 5 years. RESULTS: 14 patients were diagnosed with anti-GBM crescentic glomerulonephritis. The mean duration of symptoms was 3.6 ± 1.9 weeks. All patients presented with rapidly progressive glomerulonephritis (RPGN). Five (35.7%) patients had concomitant urinary tract infection (UTI), 2 (14.3% had underlying type 2 diabetes mellitus, 5 (35.7%) patients also had positive anti-neutrophil cytoplasmic antibodies (ANCA), and 9 (64.3%) were dialysis-dependent at presentation. Four (28.6%) patients developed diffuse alveolar hemorrhage (DAH). All patients received baseline corticosteroids, and 7 (50%) patients also received plasmapheresis. Nine (64.3%) patients were treated with CYC, and 3 (21.4%) patients received RTX. In the CYC arm, 2 (28.6%) patients died, 3 had end-stage kidney disease (ESKD) at 3 months, and 2 had chronic kidney disease (CKD) stage III at 3 months of follow-up. Two patients were lost to follow-up. In the RTX arm, all 3 patients survived with no incidence of DAH, 1 patient each had ESKD and CKD stage III, and 1 dialysis-dependent patient achieved normal kidney function at the end of 3 months. CONCLUSION: Most patients presented late with dialysis-dependent renal failure, and many had concomitant UTI. Concomitant infection causes diagnostic confusion with RPGN and DAH, which delays diagnosis and treatment. RTX as an alternative to CYC in addition to baseline corticosteroids and/or plasmapheresis and is associated with favorable outcomes.

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.

Acquired aplastic anemia complicated with anti-glomerular basement membrane disease successfully treated with immunosuppressive therapy: a case report.

BACKGROUND: Aplastic anemia (AA) is a rare but fatal disorder characterized by pancytopenia due to bone marrow hypoplasia. Anti-glomerular basement membrane disease (anti-GBM disease) is an immune complex small-vessel vasculitis that presents as rapidly progressive glomerulonephritis and/or pulmonary hemorrhage. Although both involve autoreactive T cells that are partially triggered by human leukocyte antigen (HLA)-DR15, there have been no reports of their co-existence and the treatment strategy is not well understood. CASE PRESENTATION: A 67-year-old woman presented with fever, malaise, and acute kidney injury with proteinuria and hematuria requiring hemodialysis. She was diagnosed with anti-GBM antibody disease based on high serum anti-GBM antibody titer and crescentic glomerulonephritis on a renal biopsy. Pulse administration of methylprednisolone (MP), oral prednisolone (PSL), and plasmapheresis were performed. Only 2 weeks after the diagnosis of anti-GBM disease, the patient developed pancytopenia requiring frequent blood transfusions. The blood cell count did not recover even 1 month after discontinuing the drugs that could cause pancytopenia. Bone marrow examination showed hypocellularity without abnormal infiltrates or fibrosis, which led to the diagnosis of severe acquired AA. Further HLA phenotyping revealed that she had HLA-DR15. Increased dose of PSL with the secondary MP pulse and the addition of cyclosporine improved pancytopenia. Although she remained dialysis-dependent, anti-GBM disease and pancytopenia did not recur for more than 2 years. CONCLUSIONS: We report the first case of acquired AA complicated with anti-GBM disease in an elderly woman with HLA-DR15, which was successfully treated with immunosuppressive therapy (IST). This report is valuable not only because it shows they may co-occur, but also because it provides a therapeutic option for this complex condition. It was also suggested that pancytopenia in patients with anti-GBM disease recalls serious hematologic diseases including AA that require immediate treatment based on bone marrow examination.

Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known. METHODS: A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity. RESULTS: Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, P=0.005). Antilaminin-521 autoantibodies were predominantly of IgG1 and IgG4 subclasses and significantly associated with lung hemorrhage (P=0.005), hemoptysis (P=0.008), and smoking (P=0.01), although not with proteinuria or serum creatinine at diagnosis. CONCLUSIONS: Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.

Clinical and pathological features of anti-glomerular basement membrane disease associated with membranous nephropathy: an observational study.

To investigate the clinical manifestations, pathological features, pathogenesis, treatment, and prognosis of anti-glomerular basement membrane (anti-GBM) disease with membranous nephropathy (MN). Seven patients with anti-GBM disease and concurrent MN were enrolled in this study. Control subjects included 13 patients with anti-GBM glomerulonephritis (GN) and 6 with anti-GBM disease and concurrent anti-neutrophil cytoplasmic antibodies-associated disease (anti-GBM + ANCA). Laboratory tests and pathological information were analyzed before immunosuppressive therapy or plasmapheresis administration. Prognosis was assessed in continuous follow-up. In the anti-GBM + MN group, 28.57% of patients exhibited acute kidney disease, lower than that in the anti-GBM GN group (84.62%, p = .022). None of the anti-GBM + MN or + ANCA patients exhibited hemoptysis, but 15.4% of anti-GBM GN patients did, with no significant difference (p = .720). Only 14.3% of anti-GBM + MN patients had crescentic GN. The proportion of necrosis averaged 29.0% in the anti-GBM + MN group. Survival curve analysis revealed that renal outcomes in the anti-GBM + MN group were better than those in the anti-GBM GN group (p = .019). Patients with both anti-GBM disease and MN showed atypical anti-GBM GN. They had a lower proportion of glomerular crescents and a better renal function prognosis than patients with classical anti-GBM GN. To improve renal recovery, early identification and treatment of anti-GBM disease associated with MN is needed.

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.

Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

BACKGROUND: The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. CONCLUSION: On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Successful pregnancy in a patient with pulmonary renal syndrome double-positive for anti-GBM antibodies and p-ANCA
.

BACKGROUND: Antiglomerular basement membrane (anti-GBM) antibody disease is a rare condition causing pulmonary hemorrhage and necrotizing glomerulonephritis (pulmonary renal syndrome). CASE: We report a 30-year-old woman who presented with life-threatening pulmonary hemorrhage and an active urinary sediment, with normal glomerular filtration rate in the 13th week of pregnancy. Anti-GBM antibodies in serum were negative, but perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) were detected. A renal biopsy revealed necrotizing glomerulonephritis with linear IgG deposits along the glomerular basement membrane. A diagnosis of pulmonary renal syndrome caused by anti-GBM antibodies and p-ANCA (double-positive) was made. Plasma exchange was started but had to be changed to immunoadsorption because of an allergic reaction to fresh frozen plasma. Oral steroids were introduced. The patient also received one dose of intravenous cyclophosphamide followed by two 1-g doses of rituximab. The patient responded quickly to treatment with resolution of pulmonary hemorrhage and urinary abnormalities. The infant was delivered in the 38th week of pregnancy by caesarian section. It was small for age but otherwise completely healthy with a normal B-cell count. CONCLUSION: To our knowledge, this is the first report of a double-positive pulmonary renal syndrome in pregnancy. Presentation in mid-pregnancy allowed for the application of cyclophosphamide without causing malformations and rituximab without B-cell depletion in the infant.
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Development of anti-glomerular basement membrane glomerulonephritis during the course of IgA nephropathy: a case report.

BACKGROUND: Anti-glomerular basement membrane (GBM) glomerulonephritis does not usually coexist with another glomerulonephritis such as IgA nephropathy. We present a rare case having a combination of these two diseases, and furthermore, histological evaluation could be performed before and after the development of anti-GBM glomerulonephritis over a period of only10 months. CASE PRESENTATION: A 66-year-old woman was admitted with complaints of microscopic hematuria and mild proteinuria for the past 3 years. Serum creatinine level was normal at that time. The first renal biopsy was performed. Light microscopy revealed mesangial proliferative glomerulonephritis with fibro-cellular crescents in one out of 18 glomeruli, excluding one global sclerotic glomerulus. Immunofluorescence (IF) showed IgA and C3 deposition in the mesangium. Therefore, the diagnosis was IgA nephropathy. Eight months later, the patient's serum creatinine suddenly rose to 4.53 mg/dL and urinalysis showed 100 red blood cells per high power field with nephrotic range proteinuria (12.3 g/gCr). The serological tests revealed the presence of anti-GBM antibody at the titer of 116 IU/mL. Treatments were begun after admission, consisting of hemodialysis, plasma exchange, and intravenous methylprednisolone pulse therapy. At 4 weeks after admission, the second renal biopsy was performed. Light microscopy revealed crescents in 18 of 25 glomeruli, excluding six global sclerotic glomeruli. IF showed linear IgG deposition along the GBM in addition to granular IgA and C3 deposition. Based on these findings, the diagnosis of anti-GBM glomerulonephritis and IgA nephropathy was confirmed. Renal function was not restored despite treatment, but alveolar hemorrhage was prevented. CONCLUSIONS: We report a patient with a diagnosis of anti-GBM disease during the course of IgA nephropathy. This case strongly suggests that the presence of autoantibodies should be checked to rule out overlapping autoimmune conditions even in patient who have previously been diagnosed with chronic glomerulonephritis, such as IgA nephropathy, who present an unusually rapid clinical course.

A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis.

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

Etiology and outcome of pulmonary renal syndrome: Retrospective study from a tertiary care hospitaln.

To determine the aetiology, clinical characteristics and outcome of patients admitted with pulmonary renal syndrome (PRS). This retrospective analysis was conducted at Aga Khan University Hospital from 2011 to 2015. A total of 17 adult patients admitted with PRS were included and followed up for a period of one year for the outcome of PRS as recovery, dialysis dependency or death. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) was found to be the single most frequent cause in 13 (76.4%) patients. The c o mm o n e s t c a u s e o f A AV w a s fo u n d t o b e Granulomatous polyangitis (GPA) in 10 (58.8%) followed by Microscopic angitis in 3 (17.6%) patients. Around 12 (70.5%) patients survived, 11 (64.7%) recovered while 1 patient remained dialysis dependent. Mortality rate was 29.4% and all these patients had severe alveolar haemorrhages. None of our patient died or relapsed during one year follow up.

Antiglomerular Basement Membrane Disease.

Antiglomerular basement membrane (anti-GBM) disease is a rare but life-threatening autoimmune vasculitis that is characterized by the development of pathogenic autoantibodies to type IV collagen antigens expressed in the glomerular and alveolar basement membranes. Once deposited in tissue, these autoantibodies incite a local capillaritis which manifests as rapidly progressive glomerulonephritis (GN) in 80 to 90% of patients, and with concurrent alveolar hemorrhage in ∼50%. A small proportion of cases may present with pulmonary disease in isolation. Serological testing for anti-GBM antibodies may facilitate rapid diagnosis, though renal biopsy is often required to confirm the presence of necrotizing or crescentic GN and linear deposition of autoantibody on the glomerular basement membrane. Alveolar hemorrhage may be evident clinically, or detected on imaging, pulmonary function testing, or bronchoscopy. Prompt treatment with plasmapheresis, cyclophosphamide, and steroids is usually indicated to remove pathogenic autoantibodies, to prevent their ongoing production, and to ameliorate end-organ inflammation. Alveolar hemorrhage is usually responsive to this treatment, and long-term respiratory sequelae are uncommon. Renal prognosis is more variable, though with aggressive treatment, independent renal function is maintained at 1 year in more than 80% of patients not requiring renal replacement therapy at presentation. Relapse in uncommon in anti-GBM disease, unless there is a concomitant antineutrophil cytoplasm antibody (present in 30-40%), in which case maintenance immunosuppression is recommended.