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We experienced a rare case of membranous glomerulopathy(MN) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis. A 79-year-old woman was admitted to our hospital because of pyrexia, microscopic hematuria, massive proteinuria and positive MPO-ANCA on June, 2007. We diagnosed her as MPO-ANCA-associated vasculitis accompanied by nephrotic syndrome. Intravenous methylprednisolone sodium succinate (500 mg/day for three days)therapy and oral prednisolone (40 mg/day) improved her fever, hematuria, serum CRP and MPO-ANCA titer. Renal biopsy was performed and light microscopic examination of a renal biopsy specimen containing 21 glomeruli revealed global sclerosis in 3 and thickened basement membrane in 18 of the glomeruli. Fibrocellular crescents were found in 2 and segmental necrosis in 1. Immunofluorescence microscopy showed granular staining with IgG and C3 along the capillary walls. Electron microscopic examination disclosed subepithelial dense deposits in the thickened glomerular basement membrane. To investigate the pathogenesis of MN, IgG subclass was examined by means of immunofluorescence microscopy. IgG1 and IgG4 were deposited on the glomerular capillary walls, which suggested secondary MN. However, this patient refused to take any medicines and had no disease such as infection or cancer which cause secondary MN. MPO staining was performed to investigate the relation of MPO-anti-MPO antibody immune complex in the pathogenesis of MN. The results showed only a few MPO-positive cells in the glomeruli and MPO stains on the glomerular capillary walls near the MPO-positive cells. These findings suggested that the patient had MPO-ANCA-associated glomerulonephritis superimposed on idiopathic MN. In the case of nephrotic syndrome with MPO-ANCA, we should consider the coexistence of other types of glomerulonephritis, especially MN.

Background: MPO-ANCA (myeloperoxidase anti-neutrophil cytoplasmic antibody) is closely related to the pathogenesis of MPO-ANCA-associated glomerulonephritis through MPO-positive cells and MPO-positive cell activation. Activated MPO-positive cells, including neutrophils and monocytes, cause glomerular capillary injury via enzyme release, such as MPO. We evaluated glomerular MPO-positive cell infiltration, extracellular MPO localization and glomerular endothelial cell injury in MPO-ANCA-associated glomerulonephritis., Methods: Renal specimens including 282 glomeruli obtained from 19 patients with MPO-ANCA-associated glomerulonephritis were analyzed. Enzyme-labeled antibody assay and immunofluorescence staining of MPO and CD34 were employed. MPO-staining was used to detect MPO-positive cells and extracellular MPO and CD34-staining was used to define glomerular endothelial cell injury. The number of MPO-positive cell infiltrations, and localization of MPO and CD34-staining areas were scored in each glomerulus. These scores were compared with the glomerular damage grading used by PAS and PAM staining., Results: 1) MPO-positive cells increased in number in correlation with the grade of acute glomerular injury. 2) Extracellular MPO were present close to the MPO-positive cells, along the glomerular capillary walls. 3) The CD34-staining area on the glomerular capillary wall decreased, in parallel with the acute glomerular injury grading. 4) MPO depositions along the glomerular capillary wall were shown to be associated with decreased staining of CD34, with immunofluorescence staining on the same glomerular section. 5) Several glomeruli with minor abnormalities showed focal MPO-positive cell infiltration associated with the presence of MPO along the glomerular capillary wall., Conclusion: These results suggest that MPO-positive cells and extracellular MPO play important roles in the pathogenesis of glomerular capillary injury from the early stage of MPO-ANCA-associated glomerulonephritis.

A 51-year-old male who had been working as a building wrecker for 20 years, was admitted to our hospital in June 1999 for proteinuria and hematuria examination. He started this work in 1978. Twelve years later, severe coughing and bloody sputum began and he was diagnosed as having silicosis in 1995. Urinalysis on admission showed proteinuria(294 mg/day), microhematuria(20-30/hpf), RBC cast and granular cast. High serum IgA(770 mg/dl) and high serum interleukin-6(IL-6) (3,280 pg/dl) were found. A renal biopsy showed mild mesangial matrix expansion and mesangial cell proliferation with IgA deposition, which was diagnosed as IgA nephropathy. Chest X-rays showed multiple small nodular lesions on both lung fields indicating silicosis. In Nov. 1999, he resigned from his job as a building wrecker because of increasing coughing and bloody sputum associated with body weight loss. Within 3 months after stopping this work, coughing and bloody sputum disappeared and the abnormal urinalysis findings returned to normal. Serum IgA and serum IL-6 data improved to 462 mg/dl and 2.5 pg/dl, respectively. It is suggested that silicon exposure might be related to the pathogenesis of IgA nephropathy in this patient.

Focal segmental glomerulosclerosis (FSGS) associated with type C virus (HCV) hepatitis has not been described in the literature to date. However, we experienced a 30-year-old man, who had had HCV hepatitis, developed nephrotic syndrome and was admitted to our hospital. The first renal biopsy showed FSGS which was diagnosed by light, immunofluorescent, and electron microscopic study. FSGS diagnosis was based upon the findings of focal segmental glomerular sclerosis associated with hyalinosis and foam cells, segmental deposition of IgM and C3 on glomeruli, and epithelial cell vacuolization in the Bowman's space. HCV hepatitis was treated with interferon-alpha (INF-alpha) over 6 months. The treatment brought the disappearance of not only HCV-RNA from the blood, but also the manifestation of nephrotic syndrome. Therefore, the second renal biopsy was performed, but did not reveal any great pathological improvement. Five months later after the remission, he again had an elevated HCV-RNA level and a relapse of nephrotic syndrome. He was retreated with the same therapy and achieved a second remission of nephrotic syndrome. FSGS associated with HCV hepatitis is described first and the implication of INF-therapy in the improvement of proteinuria is discussed.

We report here a case of Cogan's syndrome associated with systemic vasculitis as well as myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA)-related glomerulonephritis. A 71-year-old woman with the diagnosis of aortitis syndrome and pulmonary fibrosis for 7 years, complained of vertigo and hearing impairment. A diagnosis of serous otitis media was made. Although steroid therapy was effective, the symptoms relapsed several times. Seven months after the first manifestation of aural symptoms, she developed painful red eyes bilaterally and proteinuria. On admission, perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MOP-ANCA was detected by enzyme linked immunosorbent assay using the 363 ELISA Unit. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. A diagnosis of atypical Cogan's syndrome with systemic vasculitis and pulmonary fibrosis was made from the clinical and histological findings. As nephrotic syndrome progressed after admission, she was started on high-dose corticosteroid administration. Urinary protein and other symptoms, except for hearing acuity, improved in parallel with a decrease in the MPO-ANCA titer to normal values. While tapering the dose of corticosteroid, the MPO-ANCA titer increased again and dyspnea occurred. Although pulse methylpredonisolone therapy was performed, the patient died of respiratory failure complicated with sepsis. Postmortem lung biopsy showed pulmonary fibrosis and massive alveolar hemorrhage. The findings of this case study suggest that MPO-ANCA may be closely related to the pathogenesis of Cogan's syndrome.

It is well known that the myoglobinuric acute renal failure caused by drugs is an important clinical aspect of nephrology. On the other hand, neuroleptic malignant syndrome is an uncommon, but potentially fatal, idiosyncratic reaction to neuroleptics and is characterized by muscular rigidity, fever, autonomic dysfunction and altered consciousness. The most common serious complication of malignant syndrome is rhabdomyolysis. We investigated 10 cases with acute renal failure induced by haloperidol and other neuroleptics. At the time they developed acute renal failure, the patients were taking a wide variety of medications. However, seven of the patients who developed acute renal failure, had received haloperidol, phenothiazine and anticholinaergic drugs, and 2 cases with acute renal failure were taking lithium. Characteristic clinical manifestations of malignant syndrome were observed in 7 patients who had been administered haloperidol orally or intravenously. All of the patients with acute renal failure induced by haloperidol, lithium and other neuroleptics were treated successfully with blood purification therapy (HD or HDF). We concluded that acute renal failure associated with malignant syndrome evoked by haloperidol is an indication for blood purification therapy.

A 42-year-old female with progressive systemic sclerosis (PSS) developed rapidly progressive renal insufficiency. Renal pathology revealed crescentic glomerulonephritis (CrGN) without mucoid intimal proliferation of the interlobular arteries and fibrinoid necrosis of the afferent arterioles. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Not only anti-glomerular basement membrane antibody (anti-GBM Ab), but also myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were simultaneously detected by an enzymelinked immunosorbent assay (ELISA). She did not develop pulmonary hemorrhage. These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of serum creatinine level (over 6.0mg/dl), a high titer of MPO-ANCA (660.7 ELISA unit/ml) and anti-GBM Ab (409 units). Therefore, she was started on methylprednisolone pulse therapy and temporary hemodialysis. After immunosuppressive therapy, both antibodies titers had fallen to within the normal range. However, end-stage renal failure did not improve and maintenance hemodialysis was introduced. Recently, six patients of PSS with MPO-ANCA were first reported in Japan. These autoantibodies detected in this case strongly suggested that there may be associations between anti-GBM Ab nephritis and ANCA-related vasculitis and PSS.

We report a case of microscopic polyarteritis nodosa associated with myeloperoxidase-antineutrophil cytoplasmic autoantibodies (MPO-ANCA). A 38 year-old female was admitted to our hospital, because of proteinuria, recurrent pyrexia, polyarthralgia, abdominal pain and purpura. She had a history of severe pulmonary hemorrhage and 4 kg weight loss for 8 months. On admission perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MPO-ANCA was detected by enzyme linked immunosorbent assay. But anti-nuclear antibodies, immune complexes and anti-glomerular basement membrane antibodies were not detected. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. Skin biopsy revealed leukocytoclastic vasculitis. Diagnosis of microscopic polyarteritis nodosa was made by these clinical and histological evidence of vasculitis. As renal failure progressed after admission, corticosteroid and cyclophosphamide administration were started. Renal function and other symptoms improved paralleled with decreased MPO-ANCA titer to normal values. It is suggested that MPO-ANCA may be closely related to the pathogenesis of microscopic polyarteritis nodosa and it may be a good serological marker for diagnosis and disease activity of this disease.

We report a case of idiopathic crescentic glomerulonephritis with pulmonary hemorrhage associated with anti-myeloperoxidase antibodies (anti-MPO ab). A 74 year-old female was admitted to our hospital because of rapidly progressive glomerulonephritic syndrome and dyspnea with bloody sputum. On admission anti-MPO ab, one of anti-neutrophil cytoplasmic antibodies, were detected but anti-GBM antibodies and immune complexes were not detected. Renal biopsy showed crescentic glomerulonephritis and lung biopsy showed massive alveolar hemorrhage. Both tissue had pauci-immune deposit by immunofluorescence microscopy. Hemodialysis and steroid administration were started. Pulmonary hemorrhage was improved remarkably, but renal failure progressed rapidly to end stage kidney, then hemodialysis was continued. Although subsequent 3 years uneventful maintenance hemodialysis had been performed, she admitted to our hospital again because of progressive dyspnea with hemoptysis after upper respiratory tract infection. On admission anti-MPO ab were detected again and steroid administration was started. Pulmonary hemorrhage was improved with decreased anti-MPO ab titer. While tapering the dosis of steroid, anti-MPO ab again increased and pulmonary hemorrhage recurred. Although pulse methylprednisolone therapy and plasma exchange were performed, respiratory failure progressed rapidly and she died of sepsis. Postmortem examination showed no evidence of systemic vasculitis. In this case, titer of anti-MPO ab was associated with not only idiopathic crescentic glomerulonephritis but also with pulmonary hemorrhage. We tried to detect enzymatically active MPO in serum. Titer of serum MPO was also associated with disease activity and anti-MPO ab. It is suggested that both anti-MPO ab and serum MPO are closely related to the pathogenesis of idiopathic crescentic glomerulonephritis and pulmonary hemorrhage.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been found in patients with systemic vasculitis and crescentic glomerulonephritis. Recently two types of ANCA were identified, one is anti-myeloperoxidase antibodies (Anti-MPO Ab) stained perinuclear pattern of alcohol-fixed neutrophils by immunofluorescence test, and the other is autoantibodies with no reactivity with myeloperoxidase stained diffuse cytoplasmic pattern (C-ANCA). We investigated 59 patients with various glomerulonephritis with or without crescent to detect anti-MPO Ab and C-ANCA by an enzyme-linked immunosorbent assay. The results were as follows: 1) Anti-MPO Ab were detected only in patients with various glomerulonephritis with crescent. 2) Titers of anti-MPO Ab were high related to percentage of crescent in some cases of glomerulonephritis. 3) Titers of anti-MPO Ab were elevated at stage of cellular and fibro-cellular crescent. 4) C-ANCA were detected only in patients with Wegener's granulomatosis. These data suggested that anti-MPO Ab may play important roles in crescent formation and may be a marker of crescent formation in various glomerulonephritis.