The diagnostic suspicion for the data given (especially the anti-GBM antibodies and the presence of renopulmonary syndrome) is that of Goodpasture's syndrome. The rest of the data (seminules in the biopsy, linear IgG deposition) supports the diagnosis. Knowing this, the options are easily discarded: option 1 speaks to us of an IgA nephropathy (it is not the case because the deposits are of IgG); option 3 is also discarded, because it is not a primary GMN, like the membranous one, but a secondary glomerulopathy; option 4 is also false: the initial treatment is with corticosteroids and cyclophosphamide associated to plasmapheresis; and option 5 is also false, since the damage is not due to circulating immunocomplexes, but to antibodies deposited in the glomerular basement membrane. This leaves option 2 as true: as it has been previously said, the treatment would be performed combining corticosteroids, cyclophosphamide and plasmapheresis.

The diagnostic suspicion for the data given (especially the anti-GBM antibodies and the presence of renopulmonary syndrome) is that of Goodpasture's syndrome. The rest of the data (seminules in the biopsy, linear IgG deposition) supports the diagnosis. Knowing this, the options are easily discarded: option 1 speaks to us of an IgA nephropathy (it is not the case because the deposits are of IgG); option [HIDDEN], because it is not a primary GMN, like the membranous one, but a secondary glomerulopathy; option [HIDDEN] the initial treatment is with corticosteroids and cyclophosphamide associated to plasmapheresis; and option [HIDDEN], since the damage is not due to circulating immunocomplexes, but to antibodies deposited in the glomerular basement membrane. This leaves option [HIDDEN] as it has been previously said, the treatment would be performed combining corticosteroids, cyclophosphamide and plasmapheresis.

A 38-year-old man consults for dyspnea and hemoptysis. Blood tests show creatinine 7 mg/dL, urea 250 mg/dL and high titer positive anti-GBM (anti-glomerular basement membrane antibodies). Renal biopsy shows crescents in 75% of the glomeruli and immunofluorescence shows a linear Ig deposition pattern. Which of the following is the correct answer?

It is an IgA nephropathy with acute renal failure.

Mycophenolate mofetil is the initial treatment of choice.

Glomerular involvement is caused by the presence of circulating immunocomplexes.

Development of anti-glomerular basement membrane glomerulonephritis during the course of IgA nephropathy: a case report.

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. 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/g<subCr</sub). 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. 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.

Patient with antibody-negative relapse of Goodpasture syndrome.

Smoking in young men may trigger anti-GBM disease manifesting with hemoptysis. We present a male adolescent in whom hemoptysis was mistaken to be a sign of airway infection for several months and who later on underwent an unusual antibody-negative relapse. The 16-year-old patient had a history of smoking and therapy-refractant hemoptysis and, later, acute macrohematuria with renal insufficiency necessitating hemodialysis (initial creatinine 4.2 mg/ dl). Chest X-ray showed diffuse lung infiltration. Renal biopsy revealed linear IgG deposits along the glomerular basement membrane (GBM) and cellular crescents in 13/16 glomeruli, simultaneously increased anti-GBM antibodies were detected. Thus, anti-GBM glomerulonephritis was diagnosed. After treatment with prednisone, oral cyclophosphamide and plasmapheresis, chest X-ray and hemoptysis improved, but renal failure persisted. Anti-GBM antibodies were negative. 4 weeks later, the patient presented again with a clinical relapse of severe hemoptysis and respiratory insufficiency after smoke exposition. Despite negative anti-GBM antibodies, he was treated similarly to a relapse and after the second course of plasmapheresis the patients' general condition improved and hemoptysis subsided. During the next 10 months the patient was stable with negative antibodies. He was under intermittent hemodialysis until laboratory measurements showed improved renal function. Now, 30 months after the acute episode, the patient is off dialysis for 17 months with stable creatinine values of 1.9 - 2.4 mg/dl, and is currently being treated with antihypertensive medicaments, calcitriol, calciumacetate, natriumhydrogencarbonate and allopurinol. The prognosis of anti-GBM glomerulonephritis depends on serum creatinine and the need of dialysis at initial presentation. In these patients, one-year survival rate is 67% and 5% for kidney function. Of note, despite the unfavorable prognosis in our patient, renal function recovered after 1 year of hemodialysis treatment. It is important to consider that in patients with anti-GBM disease antibody-negative relapses are possible.

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

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). 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. 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.

[A case of anti-GBM nephritis (crescentic glomerulonephritis) associated with membranous nephropathy].

We report a case of endstage renal disease due to simultaneous occurrence of membranous nephropathy and crescentic glomerulonephritis associated with anti-GBM antibodies. The patient was a 60-year-old male and was hospitalized for prolonged anorexia and general malaise. On admission, his body temperature was 38.5 degrees C. Urinalysis revealed 3+ proteinuria and the sediment contained abundant erythrocytes. The urea nitrogen was 142.4 mg/dl, the creatinine 19.5 mg/dl, the potassium 6.47 mEq/dl and CRP 10.1 mg/dl. Anti-GBM antibodies were 1000EU/ml. Immediately after initiating hemodialysis, pulse steroid therapy, plasma exchange and continuous heparinization were performed. However, renal function had been impaired and maintenance hemodialysis was required. Histological examination of the renal specimen revealed marked epithelial crescent formation, whereas thickening of basement membrane and mesangial proliferation were not observed. By immunofluorescent staining, both bright linear and fine granular fixation of IgG and fine granular fixations of C3 along the glomerular capillary walls were observed. Electron microscopy showed subepithelial electron lucent deposits and thickening of the glomerular basement membrane, diagnostic of the advanced membranous nephropathy (stage IV).

Goodpasture's syndrome with absence of circulating anti-glomerular basement membrane antibodies: a case report.

Goodpasture's syndrome, a rare disease, is an organ-specific autoimmune disease mediated by anti-glomerular basement membrane antibodies. Its pathology is characterized by crescentic glomerulonephritis with linear immunofluorescent staining for immunoglobulin G on the glomerular basement membrane. Although rare, a few cases with absence of circulating anti-glomerular membrane antibodies have been described. The objective of this clinical case report is to describe and discuss a case of a 27-year-old white man who was hospitalized with a 1-year history of weight loss and a 1-month history of hemoptysis, with aggravation  the day before, having developed dyspnea and cough in the previous 24 hours. An analytical study showed normocytic normochromic anemia with a hemoglobin level of 7.2 g/dL and leukocytosis with normal renal function and coagulation times. A blood transfusion was performed without complications. Chest computed tomography revealed a reticulonodular infiltrate of both lungs. Bronchoscopy showed no apparent lesions. Sputum cultures, rapid urine antigens for Legionella pneumophila and Streptococcus pneumoniae, studies for Influenza, virologic markers and serologic studies for autoimmunity were all negative. At the end of the tenth day his general state deteriorated with fatigue, hematuria, and in 3 days he developed aggravation of renal function with recurrent hemoptysis and anemia. Immunosuppression with daily prednisolone 1 g administered intravenously was initiated. An urgent bronchoscopy showed no lesions. A kidney biopsy showed fibrinoid necrosis and cellular crescents. Immunofluorescence revealed a linear immunoglobulin G deposition compatible with Goodpasture's syndrome. Immunosuppressive therapy with daily cyclophosphamide 120 mg orally was added. Subsequently he was transferred to a referral center at which 21 sessions of plasmapheresis and four sessions of hemodialysis were performed with good response; he currently has no need of hemodialysis. The absence of circulating anti-glomerular basement membrane antibodies in Goodpasture's syndrome adds complexity to the diagnosis creating an unusual setting in a rare disease. In our case a kidney biopsy was essential for diagnosis and clinical approach. Studies have shown that early aggressive therapy leads to an improved prognosis. Physicians should consider tissue diagnoses such as bronchoscopy and kidney biopsy in pulmonary renal syndrome.

Anti-glomerular basement membrane antibody disease with granulomatous lesions on renal biopsy.

We present the case of a 56-year-old woman with anti-glomerular basement membrane (anti-GBM) antibody disease accompanied by granulomatous reaction in the kidney. Three months prior to admission to our kidney center, she had suffered from interstitial pneumonia and had a slightly elevated level of MPO-ANCA (13 EU). Her serum level of creatinine was normal (0.72 mg/dl) but proteinuria (1+) and hematuria (2+, 1-4/HF) were present. She was admitted to our hospital because of general fatigue, loss of appetite, high fever (over 38.5 degrees C) and a rapid decline in renal function (creatinine 8.50 mg/dl). Hemodialysis therapy was started immediately after admission. The serological study was negative for MPO-ANCA and PR3-ANCA but positive for anti-GBM antibody (139 EU). Renal biopsy demonstrated necrotizing glomeruli, cellular crescents and grauloma formation with multinucleated giant cells. Immunofluorescence microscopy revealed linear staining of IgG and C3. We diagnosed graulomatous, crescentic and necrotizing glomerulonephritis, patho-logically. She was diagnosed as having anti-GBM antibody disease because alveolar hemorrhage was absent. Steroid therapy including methylprednisolone pulse therapy (500 mg/day, 3 days) and 2 courses of plasma exchange were effective in reducing the fever, anti-GBM antibody titer and C-reactive protein level. Her renal function recovered and she was able to quit hemodialysis therapy 68 days after the start of hemodialysis and she has shown no signs of pulmonary alveolar hemorrhage to date. The present case suggests that intensive therapy may restore renal function in anti-GBM disease even though renal function was sufficiently damaged and required hemodialysis therapy and active pathological changes were observed in renal biopsy specimens.

Goodpasture syndrome manifesting as nephrotic-range proteinuria with anti-glomerular basement membrane antibody seronegativity: A case report.

The Goodpasture syndrome is an extremely rare disease, with renal and pulmonary manifestations, and is mediated by anti-glomerular basement membrane (anti-GBM) antibodies. Renal pathological changes are mainly characterized by glomerular crescent formation and linear immunofluorescent staining for immunoglobulin G on the GBM. There are few reports on the atypical course of the syndrome involving serum-negative anti-GBM antibodies. Therefore, we present a case of Goodpasture syndrome that presented with nephrotic-range proteinuria and was seronegative for anti-GBM antibodies. A 38-year-old Chinese man presented with a lung lesion that was discovered by physical examination a month prior to presentation. The chief concern was occasional hemoptysis without fever, cough, chest pain, and edema. Laboratory testing revealed that the urinary protein level and urine erythrocyte count were 7.4 g/24 hours and 144/high-power field (HPF), respectively. Serological testing for anti-GBM antibodies was negative. Chest computed tomography revealed multiple exudative lesions in both lungs, indicating alveolar infiltration and hemorrhage. Electronic bronchoscopy and pathological examination of the alveolar lavage fluid indicated no abnormalities. However, kidney biopsy suggested cellular crescent formation and segmental necrosis of the globuli, with linear IgG and complement C3 deposition on the GBM. These findings were consistent with the diagnosis of anti-GBM antibody nephritis. The patient underwent 7 sessions of double filtration plasmapheresis. He was also administered with intravenous methylprednisolone and cyclophosphamide. After renal function stabilization, he was discharged under an immunosuppressive regimen comprising of glucocorticoids and cyclophosphamides. Three months later, follow-up examination revealed that the 24-hour urine protein had increased to 13 g. Furthermore, the urine erythrocyte count was 243/HPF. After a 6-month follow-up, the patient achieved partial remission, with a proteinuria level of 3.9 g/24 hours and a urine erythrocyte count of 187/HPF. This extremely rare case of Goodpasture syndrome manifested with seronegativity for anti-GBM antibodies and nephrotic-range proteinuria. Our findings emphasize the importance of renal biopsy for the clinical diagnosis of atypical cases. Furthermore, because renal involvement achieved only partial remission despite therapy, early detection and active treatment of the Goodpasture syndrome is necessary to improve the prognosis of patients.

An unusual case of IgA-mediated anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease is mediated by circulating autoantibodies, principally IgG, targeted at the type IV collagen of GBM. The IgA variant of anti-GBM disease has rarely been described. We report a 65-year-old man with uremia, undergoing hemodialysis, who was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis. Circulating IgA anti-GBM antibody was found, as well as the presence of significant IgA deposition in a linear pattern along the GBM, suggesting an anti-GBM antibody-mediated disease. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.

[Case of rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody in the course of MPO-ANCA-associated pachymeningitis].

A 56-year-old female developed rapidly progressive glomerulonephritis in the course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated pachymeningitis that had been found four years previously. On admission, her serum creatinine increased from 0.8 mg dL to 1.84 mg dL and to 3.66 mg dL every 3 to 4 weeks. Urinalysis revealed that urinary protein excretion was 1.25 g day and 3+ hematuria. MPO-ANCA titer was found to be 50 EU and anti-glomerular basement membrane (GBM) antibody was also elevated to as high as 174 EU. Renal pathology revealed cellular to fibrocellular crescents in 21 out of 23 glomeruli with interstitial inflammation and fibrosis. Immunohistochemistry with anti IgG antibody showed linear staining along the glomerular capillary walls. Following plasma exchange and methylprednisolone pulse therapy, oral prednisolone at a dose of 50 mg day was instituted, but without significant effect. Subsequent cyclophosphamide pulse therapy was effective, resulting in the stabilization of serum creatinine at 2 mg dL and disappearance of urine abnormalities. In addition, the MPO-ANCA titer and anti-GBM antibody titer of the patient decreased to within the normal range in one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases. one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases.

[A case of Goodpasture's syndrome with massive pulmonary hemorrhage ameliorated by cyclophosphamide pulse therapy].

A 22-year-old woman was admitted to our hospital for evaluation of fever, renal dysfunction, and a 3-month-history of macrohematuria. Laboratory evaluation revealed proteinuria (1.8 g/day), hypoproteinemia, microcytic microchromic anemia, renal failure (blood urea nitrogen 30.3 mg/dl, serum creatinine 4.0 mg/dl), and positive serum antiglomerular basement membrane (anti-GBM) antibody. Renal biopsy revealed cellular crescents in all 8 glomeruli and partial rupture of the GBM. The interstitium showed severe inflammatory cell infiltration. Immunofluorescent examination revealed linear deposits of IgG and C3 along the GBM. Pulmonary biopsy revealed linear deposits of IgG along the alveolar basement membrane in the immunofluorescent examination. A diagnosis of Goodpasture's syndrome was made because all of the diagnostic criteria were fulfilled. After admission, the patient's renal function deteriorated rapidly. Hemodialysis was started, and the patient was treated with methylprednisolone pulse therapy and oral prednisolone with double filtration plasma pheresis (DFPP). However, her renal function did not improve. On the 30th hospital day, she showed hemoptysis, and a chest X-ray and CT revealed massive bilateral pulmonary hemorrhage. Despite treatment with pulsed methylprednisolone, oral prednisolone (80 mg/day), and DFPP, the pulmonary hemorrhage improved only transiently, worsening again 5 days later. Cyclophosphamide pulse therapy was administered. After this treatment, the patient's pulmonary manifestations and pulmonary hemorrhage improved. At the present time she is on maintenance dialysis therapy without pulmonary manifestations. These findings suggest that cyclophosphamide pulse therapy is effective against Goodpasture's syndrome with massive pulmonary hemorrhage showing resistance to other conventional therapy.

IgA variant of anti-glomerular basement membrane glomerulonephritis associated with pulmonary hemorrhage and microangiopathic hemolytic anemia.

A 70-year-old man with uremia was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgA along the glomerular basement membrane (GBM). No thrombotic microangiopathy was noted on renal biopsy. Circulating IgG anti-GBM antibody was not detected, and IgA anti-GBM antibody was not tested. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.

[Acute kidney failure in glomerulonephritis and in angiitis].

Some cases of postinfectious glomerulonephritis initially are oligoanuric. Renal biopsy is essential to distinguish the purely endocapillary and exsudative form from that with endo- and extracapillary proliferation. The former characterises spontaneously regressive poststreptococcal glomerulonephritis, which is now rare, whilst the latter is caused by various strains of gram-positive and gram-negative strains and entails a much less favourable outcome in terms of renal and patient survival. Acute renal failure is a common complication of angiitis, mainly polyarteris nodosa (PAN) and Wegener granulomatosis. A third variety of crescentic glomerulonephritis is due to anti-glomerular basement membrane (GBM) antibodies, with or without pulmonary haemorrhage. Glomerular immunofluorescence discloses a typical pattern of linear IgG deposits along the GBMs. Treatment based on plasma exchanges, corticosteroids and alkylating agents can prevent end stage renal failure when undertaken early. Other glomerulopathies may be complicated with acute renal failure, including haematuric forms of IgA nephropathy.

[A case of anti-basement membrane (BM) mediated disease presenting renal and pulmonary symptoms by divergent timing].

A case of 49-year-old man with anti-GBM antibody and who manifested pulmonary and renal symptoms at divergent times. Thirty-six years previously, renal disease with unneglectable degree of proteinuria was noticed. One month before admission, he was found by chance to have elevated serum creatine (Scr); 3.4 mg/dl. At admission, his Scr was 13.7 mg/dl and Hb 12.7 g/dl, TP 5.2 g/dl with 3+ proteinuria and no glucosuria. He was a heavy smoker and remained so while admitted. Renal biopsy presented fibrocellular crescents in 100% of glomeruli with striking tubulointerstitial involvement. Immunofluorescence showed linear IgG deposition along the glomerular capillary wall. Hemodialysis was instituted, and after 13 hospital days, anti-GBM antibody at admission was high at 128 U, with negative PANCA. Plasmapheresis was also performed, but on the next day pulmonary hemorrhage occurred with a concomitant rise of anti-GBM to 250 U. Thus, steroid pulse therapy was conducted in combination with plasmapheresis. Pulmonary hemorrhage subsided along with lowering of anti-GBM (48 U), but renal failure persisted. The patient died of septicemia. Based on the clinical course of the case, the term "anti-BM mediated disease" may more properly delineate the entity of the disease rather than the classical eponym "Goodpasture's disease" which requires coexistence of pulmo- and renal manifestations for definition.

[An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

[An experience of treatment of double positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and anti-glomerular basement membrane antibodies in Goodpasture's syndrome onset of crescentic glomerulonephritis].

A 68-year-old woman was admitted to Kinki University Hospital because of progressive renal failure. She had been well until two months before admission. Laboratory data were as follows: serum creatinine 4.1 mg/dl, BUN 69 mg/dl, MPO-ANCA 33 EU, anti-glomerular basement membrane antibodies (AGBMA) 118 U. Histological findings showed cellular and fibrocellular crescents in many glomeruli. Therefore, we diagnosed rapidly progressive glomerulonephritis (RPGN) due to MPO-ANCA and anti-GBM associated renal disease. The patient was started on prednisolone and double filtration plasmapheresis (DFPP) therapy. Subsequently, the values of MPO-ANCA and AGBMA decreased. However, the patient's condition suddenly worsened and she died of interstitial pneumonia. Autopsy examination revealed crescentic glomerulonephritis and alveolar hemorrhage with linear deposition of IgG along the glomerular and alveolar capillary walls by immunofluorescence studies. We considered this to be a rare case of Goodpasture's syndrome associated with not only anti-GBM antibodies, but also MPO-ANCA.

A Case Report of Crescentic Glomerulonephritis With Positive Serum Anti-glomerular Basement Membrane Without Linear Glomerular Basement Membrane Immunofluorescent Staining.

Anti-glomerular basement membrane (anti-GBM) disease is an autoimmune disorder characterized by the production of circulating immunoglobulin G (IgG) antibodies that affect the kidneys and lungs, mainly in the form of rapidly progressive crescentic glomerulonephritis and pulmonary hemorrhage. Typically diagnosed on tissue biopsy, findings mainly include glomerular crescent formation, bright linear staining of GBM for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Variation in the laboratory results, where histological findings of linear IgG IF staining were present in the absence of circulating anti-GBM antibodies, have recently led to the use of the term "atypical anti-GBM disease," which usually has a distinct benign clinical outcome as compared to typical anti-GBM disease. We report a case of a middle-aged woman who presented with renal failure without lung involvement. Upon further investigation, the patient was found to have strongly positive serum anti-GBM antibodies, but the tissue biopsy did not show typical findings of the anti-GBM disease. The patient showed modest improvement after multiple sessions of plasmapheresis and steroids, with stabilization of her renal parameters after the initial response. In our case, we will address the possibilities of the discrepancies between the serological and histopathological findings.

[Goodpasture syndrome: treatment initiation with plasmapheresis before histologic diagnostic verification].

A 28 years old male patient presented, after a history of previous recurrent hemoptysis, with diffuse bilateral air space consolidation at chest radiography (CXR). Within 48 hours, partial respiratory insufficiency developed and required intubation. On a clinical and roentgenographic basis, the diagnosis of a Goodpasture syndrome was suspected. Plasmapheresis and immunosuppressive therapy with prednisone and cyclophosphamide were started immediately. Three days after admission, macrohematuria developed and serum creatinine began to rise to a maximum of 3.9 mg/dl. Totally, 13 plasmaphereses were performed within 27 days. Clinical, laboratory and radiological findings improved markedly. 30 days after admission, the patient was discharged and followed on an outpatient basis. Serum creatinine eventually decreased to 1.1 mg/dl. Initially, circulating antibodies against glomerular basement membrane (GBM) were positive, controls remained negative. Renal biopsy was performed after the acute phase and showed glomerulonephritis and linear immunoglobulin deposition along the GBM. Radiologic findings at CXR and high resolution computed tomography are demonstrated.

Anti-glomerular basement membrane glomerulonephritis with subsequent pulmonary hemorrhage in the course of pulmonary tuberculosis.

A 66-year-old man with uremia and on hemodialysis was referred to our hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure accompanied by hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). Circulating IgG anti-GBM antibody was not detected. Because the findings of renal biopsy suggested anti-GBM disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture submitted on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immunosuppressive agents were discontinued and antituberculous agents were administrated. No relapse of pulmonary hemorrhage occurred during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement             membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is characterized by             crescentic glomerulonephritis with immunoglobulin G (IgG) autoantibodies to the             non-collagenous (NC1) domain of α3(IV) collagen presenting along the GBM. The             patient clinically manifests with rapidly progressive glomerulonephritis (RPGN)             with pulmonary hemorrhage (Goodpasture syndrome). In rare cases, other immunocomplexes             of IgA or IgM are involved, but their specificities have not been determined.             We report a rare case of a 31-year-old female who was diagnosed as having anti-GBM             disease with extensive IgA deposits in the mesangium. This patient presented heavy             hematuria, proteinuria with increasing creatinine, but no lung hemorrhage. Renal             biopsy showed crescentic glomerulonephritis (type Ⅰ) with strong IgA (3+) as lump             and branch shape. Therapies with pulse methylprednisolone, plasmapheresis and             cyclophosphamide administration were less effective. This case is different from             the present type Ⅰ crescentic glomerulonephritis and the specificity of IgA deposits             may implicate the pathogenesis of anti-GBM disease.

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 m<sup2</sup 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.

[A case of rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody in the course of MPO-ANCA positive interstitial pneumonia].

A 78-year-old man developed rapidly progressive glomerulonephritis (RPGN) in the course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive UIP that had been found four years previously. When UIP was diagnosed, the MPO-ANCA titer was low and urine was negative for proteinuria and hematuria. On admission, his serum creatinine increased to 16.89 mg/dL and hemoglobin decreased to 5.2 g/dL. Urinalysis revealed that urinary protein excretion was 0.423 g/day and hematuria (30-40/HPF). The MPO-ANCA titer increased to 95.6 U/mL and anti-glomerular basement membrane (GBM) antibody titer elevated to 140 EU. Renal pathology revealed cellular crescents in 10 out of 11 glomeruli excluding two global sclerotic glomeruli. Immunofluorescence showed heavy linear deposits of IgG and C3 along the GBM. Treatments were begun after admission with hemodialysis and intravenous methylprednisolone pulse therapy, oral prednisolone at the dose 30 mg/day. Both MPO-ANCA and anti-GBM antibody were within the normal range after four months. However, the renal function was not restored despite treatment and he died of pulmonary infectious disease after six months from the onset of RPGN. Recently, many cases of RPGN with both MPO-ANCA and anti-GBM antibody have been reported. In this case, persistent UIP-associated MPO-ANCA appeared to have triggered RPGN by anti-GBM antibody.

Crescentic glomerulonephritis in children.

To date, there is insufficient knowledge about crescentic glomerulonephritis (cGN), the most frequent immunologic cause of acute kidney injury in children. Over a period of 16 years, we retrospectively analyzed kidney biopsy results, the clinical course, and laboratory data in 60 pediatric patients diagnosed with cGN. The underlying diseases were immune complex GN (n = 45/60, 75%), including IgA nephropathy (n = 19/45, 42%), lupus nephritis (n = 10/45, 22%), Henoch-Schoenlein purpura nephritis (n = 7/45, 16%) and post-infectious GN (n = 7/45, 16%), ANCA-associated pauci-immune GN (n = 10/60, 17%), and anti-glomerular basement-membrane GN (n = 1/60, 2%). Patient CKD stages at time of diagnosis and at a median of 362 days (range 237-425) were CKD I: n = 13/n = 29, CKD II: n = 15/n = 9, CKD III: n = 16/n = 7, CKD IV: n = 3/n = 3, CKD V: n = 13/n = 5. Course of cGN was different according to class of cGN, duration of disease from first clinical signs to diagnosis of cGN by biopsy, percentage of crescentic glomeruli, amount of tubular atrophy/interstitial fibrosis and necrosis on renal biopsy, gender, age, nephrotic syndrome, arterial hypertension, dialysis at presentation, and relapse. Forty-eight/60 children were treated with ≥ 5 (methyl-) prednisolone pulses and 53 patients received oral prednis(ol)one in combination with mycophenolate mofetil (n = 20), cyclosporine A (n = 20), and/or cyclophosphamide (n = 6), rituximab (n = 5), azathioprine (n = 2), tacrolimus (n = 1), and plasmapheresis/immunoadsorption (n = 5). The treatment success of cGN is dependent on early diagnosis and aggressive therapy, as well as on the percentage of crescentic glomeruli on renal biopsy and on the underlying type of cGN. CsA and MMF seem to be effective alternatives to cyclophosphamide.

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

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. 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. 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.

Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy.

Anti-glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

[A case of anti-GBM-antibody positive rapidly progressive glomerulonephritis who was weaned from hemodialysis after combination therapy with steroid and plasmapheresis].

We report an anti-GBM antibody-positive crescentic glomerulonephritis patient who benefitted from maintenance hemodialysis 4 months after the initial treatment, which included steroid pulse therapy and plasma exchange. A-29-year-old male was referred to our hospital because of high fever, abnormal urinary findings (leukocytes 3+, protein 2+, occult blood 3+) and a moderate degree of azotemia(S-Cr 2.9 mg/dl). C-reactive protein (CRP) was 18.9 mg/dl and antibiotics were administered intravenously for 7 days under the diagnosis of pyelonephritis. High fever persisted, however, and S-Cr increased to 9.2 mg/dl even though a sufficient volume of urine was maintained. Blood and urine cultures were negative for bacteria. A kidney biopsy was performed and cellular crescents were observed around the glomeruli. No abnormal finding was observed in the lung and the nasopharyngeal region. To treat the crescentic glomerulonephritis, steroid and cyclophosphamide were administered while hemodialysis was carried out simultaneously. Although P-ANCA and C-ANCA were negative, anti-GBM antibody was proven to be positive thereafter (169 U) and six sessions of plasmapheresis were additionally performed to remove the antibody. Two months after the last plasmapheresis, the reduced urine volume (300 ml/day) gradually returned to normal. Hemodialysis was terminated because the S-Cr concentration reached a plateau at 4 mg/dl. Repeated biopsy revealed marked glomerulosclerosis, hence hypertension treatment and a low protein diet were ordered. In conclusion, residual renal function might improve even after 4 months of hemodialysis in cases of intensively treated anti-GBM-positive crescentic glomerulonephritis, though consecutive renoprotective therapy is required.

Rapidly progressive glomerulonephritis

Classification RPGN can be classified into three types, based upon the immunofluorescence patterns: Type I Accounting for approximately 20% of RPGN, type I RPGN, also called anti-GBM glomerulonephritis, is characterized by the presence of autoantibodies directed against type IV collagen (specifically, the noncollagenous region of its α3 chain) in the glomerular basement membrane (GBM). Some cases are associated with antibodies directed against the basement membrane of lung alveoli, producing Goodpasture syndrome. The majority of type I disease, however, features anti-GBM antibodies alone; these cases are considered idiopathic. Type II Characterized by deposition of immune complexes in glomerular tissues, type II RPGN accounts for 25% of cases. Any immune complex disease—including systemic lupus erythematosus, acute proliferative glomerulonephritis, Henoch–Schönlein purpura, and IgA nephropathy—that involves the glomerulus may progress to RPGN if severe enough.

Atypical Anti-Glomerular Basement Membrane Disease With Diffuse Crescentic Membranoproliferative Glomerulonephritis: Case Report and Review of Literature.

Anti-glomerular basement membrane (anti-GBM) disease occurs in fewer than two cases per million population. Patients usually present with features of rapidly progressive glomerulonephritis (RPGN) with or without pulmonary involvement. Anti-GBM disease is classically diagnosed by both demonstrating GBM linear immunofluorescence staining on kidney biopsy and detecting anti-GBM antibodies in serum. More than 90% of patients with anti-GBM disease either become dialysis-dependent or die if left untreated. Here, we report a 37-year-old man who presented with bilateral lower limb edema, hypertension, acute kidney injury (creatinine of 212 μmol/L), microscopic hematuria, and nephrotic range proteinuria (15 g/day). His kidney biopsy showed diffuse crescentic membranoproliferative glomerulonephritis and bright linear staining of GBM by immunoglobulin G consistent with anti-GBM disease; however, serum anti-GBM antibodies were negative. The patient was diagnosed with atypical anti-GBM disease and treated aggressively with intravenous pulse steroids, plasmapheresis, oral cyclophosphamide, and oral prednisolone with significant improvement in kidney function and proteinuria. Atypical anti-GBM disease should be considered in patients presenting with RPGN, even in the absence of serum anti-GBM antibodies. Early diagnosis and aggressive treatment in such cases are warranted to prevent irreversible kidney damage as the course of the disease might not be as benign as previously thought.

Effectiveness of Plasmapheresis in a Patient with Anti-glomerular Basement Membrane Antibody Glomerulonephritis with Advanced Kidney Dysfunction.

Patients with anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) have severe kidney dysfunction, leading to end-stage renal disease. The effect of plasmapheresis and immunosuppressive treatment in patients with severe glomerular changes is controversial. A 62-year-old man was admitted with rapidly progressive glomerulonephritis and diagnosed with anti-GBM GN. He required hemodialysis. All glomeruli in the kidney biopsy specimen had cellular crescents without fibrotic changes, suggesting reversible damage. He was treated with plasmapheresis until the anti-glomerular basement membrane antibodies disappeared. His kidney function recovered, and dialysis was able to be discontinued. Frequent plasmapheresis in patients with dialysis-dependent anti-GBM GN may improve the kidney prognosis.

Rapidly progressive glomerulonephritis

Diagnosis Serum analysis often aids in the diagnosis of a specific underlying disease. The presence of anti-glomerular basement membrane (GBM) antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN; and type III and idiopathic RPGN are frequently associated with anti-neutrophil cytoplasmic antibodies (ANCA)-positive serum. Impaired kidney function in an individual who has had the condition for fewer than three months is characteristic of RPGN. An ultrasonographic examination of the abdomen should be obtained. Although the presence of sediment in the urine on examination can indicate proliferative glomerulonephritis, many cases of rapidly progressive glomerulonephritis need a renal biopsy to make a diagnosis. Classification RPGN can be classified into three types, based upon the immunofluorescence patterns:

Membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli. MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults. It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not. Type There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood. Type I Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits. It is believed to be associated with the classical complement pathway. Type II

Monoclonal gammopathy of renal significance

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) involves monoclonal immunoglobulins (usually IgG) depositing in the glomeruli and activating compliment leading to glomerular inflammation. Light microscopy shows a membranoproliferative, endocapillary proliferative or membranous glomerulonephropathy with electron dense deposits in the glomeruli being present on electron microscopy. The lesions stain positive for the Ig (usually IgG) as well as compliment; leading to granular immunofluorescent deposits in the mesangium and glomerular basement membrane.

Glomerulonephritis

Rapidly progressive glomerulonephritis, also known as crescentic GN, is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a nephritic syndrome. In management, steroid therapy is sometimes used, although the prognosis remains poor. Three main subtypes are recognised: Type 1 is Goodpasture syndrome, an autoimmune disease also affecting the lung. In Goodpasture syndrome, IgG antibodies directed against the glomerular basement membrane trigger an inflammatory reaction, causing a nephritic syndrome and the coughing up of blood. High dose immunosuppression is required (intravenous methylprednisolone) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.