Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
Female ; Humans ; Antibodies, Antineutrophil Cytoplasmic ; Organizing Pneumonia ; Autoantibodies ; Glomerulonephritis ; Anti-Glomerular Basement Membrane Disease ; Pneumonia ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications*

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.
Adult ; Anti-Glomerular Basement Membrane Disease ; Antibodies ; Antigen-Antibody Complex ; Azotemia ; Basement Membrane ; Biopsy ; Cyclophosphamide ; Female ; Glomerulonephritis ; Glomerulonephritis, IGA ; Hematuria ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Methylprednisolone ; Nephritis ; Proteinuria

Diffuse alveolar hemorrhage (DAH) is a life-threatening and medical emergency that can be caused by numerous disorders and presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Early bronchoscopy with bronchoalveolar lavage is usually required to confirm the diagnosis and rule out infection. Most cases of DAH are caused by capillaritis associated with systemic autoimmune diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, anti-glomerular basement membrane disease, and systemic lupus erythematosus, but DAH may also result from coagulation disorders, drugs, inhaled toxins, or transplantation. The diagnosis of DAH relies on clinical suspicion combined with laboratory, radiologic, and pathologic findings. Early recognition is crucial, because prompt diagnosis and treatment is necessary for survival. Corticosteroids and immunosuppressive agents remain the gold standard. In patients with DAH, biopsy of involved sites can help to identify the cause and to direct therapy. This article aims to provide a general review of the causes and clinical presentation of DAH and to recommend a diagnostic approach and a management plan for the most common causes.
Adrenal Cortex Hormones ; Anemia ; Anti-Glomerular Basement Membrane Disease ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Autoimmune Diseases ; Biopsy ; Bronchoalveolar Lavage ; Bronchoscopy ; Capillaries ; Emergencies ; Hemoptysis ; Hemorrhage ; Humans ; Immunosuppressive Agents ; Lupus Erythematosus, Systemic ; Pulmonary Alveoli ; Transplants ; Vasculitis

Up to 40% of patients with anti-glomerular basement membrane (GBM) disease, which is a rare autoimmune disorder usually manifesting as rapidly progressive glomerulonephritis (RPGN), are positive for circulating anti-neutrophil cytoplasmic antibody (ANCA). Many previous reports showed poor outcomes in these "double-positive" patients. We report a patient with perinuclear (p)-ANCA positive anti-GBM disease who presented with RPGN and required hemodialysis. Plasmapheresis and steroid and cyclophosphamide therapy were initiated following renal biopsy and resulted in normalization of anti-GBM antibody and p-ANCA titers, recovery of renal function, and discontinuation of hemodialysis. This case suggests that aggressive immunosuppression with plasmapheresis in patients who are p-ANCA positive with anti-GBM disease should be considered, even in those with severe renal dysfunction.
Anti-Glomerular Basement Membrane Disease ; Antibodies, Antineutrophil Cytoplasmic ; Autoantibodies ; Basement Membrane ; Biopsy ; Cyclophosphamide ; Glomerulonephritis ; Hemorrhage ; Humans ; Immunosuppression ; Lung Diseases ; Plasmapheresis ; Renal Dialysis

OBJECTIVETo investigate the clinical and pathologic characteristics of anti-glomerular basement membrane(GBM) disease with normal renal function.

METHODSThe clinical and pathologic data of 6 patients with anti-GBM disease and normal renal function in Peking Union Medical College Hospital were reviewed retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired renal function in the same period in the same hospital were enrolled as the control group. Factors that may influence the prognosis were analyzed.

RESULTSSix (17.1%) of all 35 patients maintained normal renal function for 12-133 months during follow-up. Five patients had microhematuria and proteinuria, one had pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the glomerular capillary walls by immunofluorescence. As shown by normal light microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a large amount of fibrinoid necrosis of glomerular capillary walls were observed in different patients; however, most pathological changes were mild. Five of these six patients were treated with immunosuppressive drugs and/or plasma exchange. Compared with the control group, the 6 patients with normal renal function had significantly higher hemoglobin[(77.97±20.62 vs.(99.67±19.80 g/L P=0.024], lower titers of anti-GBM antibody[(224.34 ± 145.79 vs.(80.23 ± 85.73 EU/ml P=0.027], and lower ratio of glomeruli with crescents[(0.58±0.29 vs.(0.17±0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for 12-133 months, among whom 4 patients achieved complete remission and 2 had mild proteinuria and microhematuria.

CONCLUSIONAnti-GBM disease with normal renal function is not uncommon. Most patients have mild pathologic changes and good prognosis.

Adult ; Anti-Glomerular Basement Membrane Disease ; pathology ; physiopathology ; Female ; Follow-Up Studies ; Humans ; Kidney ; physiopathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVETo examine the cellular components at different stages of the crescent formation in four most common types of human crescentic glomerulonephritis (CGN), including anti-GBM disease (GBM-CGN), crescentic IgA nephropathy (IgA-CGN), ANCA associated pauci-immune CGN (ANCA-CGN) and crescentic lupus glomerulonephritis (LN-CGN).

METHODSRenal biopsy specimens of patients with GBM-CGN (n = 10), IgA-CGN (n = 12), ANCA-CGN (n = 12), and LN-CGN (n = 11) were selected. Immunohistochemistry was adopted to identify the cellular components using different cell markers including cytokeratin (PEC), CD68 (macrophage), nestin (podocyte), podocalyxin (podocyte), CD3 (lymphocyte), CD15 (neutrophil) and PCNA.

RESULTSThere were different subtypes of cell components identified during the formation of a cellular crescent in 4 different types of human CGN. Mainly of PEC 11.4 (0.0, 95.0)%, macrophage 8.0 (0.0, 35.0)% and podocyte 5.5 (0.0, 22.0)% and their constitutive percentages were different among various CGNs (P < 0.01). In all the CGNs studied, there were 50% of cells were negative to all the cell markers adopted for this expeiment. Podocalyxin positive cells 0.5 (0.0, 9.6)% were significantly less than nestin positive cells 5.5 (0.0, 22.0)% in all CGNs. PCNA positive cells were 44.7 (16.7, 83.3)% in the cellular crescent of all CGNs and co-localized with nestin (38/45 cases), CK (42/45 cases) or CD68 (24/45 cases).

CONCLUSIONSPEC, macrophage and podocyte might play important roles in the formation of crescents. The staining disparity of nestin and podocalyxin indicates that podocyte dedifferentiation may occur during the crescent formation. PEC, podocytes and macrophages may participate in the formation of crescent in common CGNs through active cellular proliferation.

Anti-Glomerular Basement Membrane Disease ; metabolism ; pathology ; Antibodies, Antineutrophil Cytoplasmic ; metabolism ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Cell Proliferation ; Epithelial Cells ; metabolism ; pathology ; Glomerulonephritis ; classification ; metabolism ; pathology ; Glomerulonephritis, IGA ; metabolism ; pathology ; Humans ; Intermediate Filament Proteins ; metabolism ; Keratins ; metabolism ; Lupus Nephritis ; metabolism ; pathology ; Macrophages ; metabolism ; pathology ; Nerve Tissue Proteins ; metabolism ; Nestin ; Podocytes ; metabolism ; pathology ; Proliferating Cell Nuclear Antigen ; metabolism ; Sialoglycoproteins ; metabolism

Adolescent ; Anti-Glomerular Basement Membrane Disease ; pathology ; Diagnosis, Differential ; Granulomatosis with Polyangiitis ; pathology ; Humans ; Kidney ; pathology ; Lung ; pathology ; Lupus Erythematosus, Systemic ; pathology ; Male

Anti-glomerular basement membrane (Anti-GBM) nephritis is an autoimmune disorder characterized by rapidly progressive crescentic glomerulonephritis (RPGN). The treatment of anti-GBM nephritis with plasmapheresis, steroids and immunosuppressant has improved outcomes. An early diagnosis is essential for the survival of patients and a recovery of renal function. The diagnosis of anti-GBM disease has been traditionally based on the demonstration of linear deposits of immunoglobulins along the glomerular basement membrane by immunofluorescence (IF) microscopy. However, a kidney biopsy cannot always be easily performed in such ill patients. Recent development of specific enzyme immunoassays for anti-GBM antibody in the serum has made possible a provisional diagnosis without a kidney biopsy. A 46-year-old male patient with hypertension and hepatitis B presented with generalized edema and general weakness. Laboratory findings were compatible with acute renal failure and nephrotic syndrome with positive serum anti-GBM antibodies. After plasmapheresis with steroid pulse therapy, renal biopsy was performed and diagnosed as membranoproliferative glomerulonephritis (MPGN) with granular deposit of Ig G and C3. Follow-up antibody titers were negative. This case demonstrates the possibility of false-positive anti-GBM antibody in the serum. Therefore, enzyme immunoassay for anti-GBM antibody should be used only as a screening or follow-up test in patients that have been confirmed positive by IF microscopy.
Acute Kidney Injury ; Anti-Glomerular Basement Membrane Disease ; Antibodies ; Autoantibodies ; Basement Membrane ; Biopsy ; Early Diagnosis ; Edema ; False Positive Reactions ; Fluorescent Antibody Technique ; Follow-Up Studies ; Glomerular Basement Membrane ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative ; Hepatitis B ; Humans ; Hypertension ; Immunoenzyme Techniques ; Immunoglobulins ; Kidney ; Male ; Mass Screening ; Microscopy ; Middle Aged ; Nephritis ; Nephrotic Syndrome ; Plasmapheresis ; Steroids

PURPOSE: Growing data on the relationship between cytokine expression and the progression of renal diseases make these cytokines potential targets for therapeutic interventions. Weexamined the helper T1-cell- and macrophage-associated cytokines in anti-glomerular basement membrane (GBM) antibody-induced nephritis in mice and their temporal relationships with renal tissue fibrosis. METHODS: Kidneys were harvested on days 1, 3, 7, 11, and 16 after glomerulonephritis was induced with anti-GBM antibody. The progression of renal fibrosis was serially monitored to quantitate the accumulation of cortical extracellular matrix, and various cytokines were measured simultaneously. RESULTS: A single injection of anti-GBM antibody successfully produced severe crescentic glomerulonephritis. Proteinuria increased abruptly and both mesangial matrix expansion and interstitial fibrosis progressed rapidly. Cortical fibronectin and type III collagen increased continuously, reaching a peak on day 7, and the deposition of type III collagen followed the same pattern, in parallel with that of urinary transforming growth factor 1 (TGF-1) expression. Serial cytokine measurements revealed a sustained increase in interleukin (IL) 6 and monocyte chemoattractant protein 1 (MCP1) from day 3, but neither IL12, IL18, nor interferon changed significantly. Real-time polymerase chain reaction confirmed these features at the transcription level. CONCLUSION: MCP1 and IL6 correlated with the progression of renal fibrosis, with no increase in Th1- inducing cytokines. This confirms MCP1 and IL6 as attractive therapeutic targets for renal fibrosis in crescentic glomerulonephritis.
Animals ; Anti-Glomerular Basement Membrane Disease ; Autoantibodies ; Basement Membrane ; Chemokine CCL2 ; Collagen Type III ; Cytokines ; Extracellular Matrix ; Fibronectins ; Fibrosis ; Glomerulonephritis ; Interferons ; Interleukin-12 ; Interleukin-18 ; Interleukin-6 ; Interleukins ; Kidney ; Mice ; Nephritis ; Proteinuria ; Real-Time Polymerase Chain Reaction ; Transforming Growth Factors

Anti-glomerular basement membrane disease is a rare autoimmune disease characterized by rapidly progressive renal failure and/or pulmonary hemorrhage. The presence of severe crescentic glomerular inflammation with linear deposition of immunoglobulin G along the glomerular basement membrane is pathognomonic. Because renal function is rapidly and often irretrievably destroyed, many patients require hemodialysis all through their lifetime. We report a case of 33 year(s)-old man who was diagnosed as anti-glomerular basement membrane disease without pulmonary hemorrhage. The patient was treated with pulse methylprednisolone and plasmapheresis followed by oral corticosteroid and cyclophosphamide. His renal function was successfully recovered with early diagnosis and aggressive treatment.
Adrenal Cortex Hormones ; Anti-Glomerular Basement Membrane Disease ; Autoimmune Diseases ; Cyclophosphamide ; Early Diagnosis ; Glomerular Basement Membrane ; Hemorrhage ; Humans ; Immunoglobulin G ; Immunosuppression ; Inflammation ; Methylprednisolone ; Plasmapheresis ; Renal Dialysis ; Renal Insufficiency