Azurocidin-specific-ANCA-related idiopathic necrotizing crescentic glomerulonephritis

An 80-year-old woman who had rapidly progressive glomerulonephritis unaccompanied by systemic vasculitis is described. On renal biopsy, she showed necrotizing crescentic glomerulonephritis by light microscopy and pauci-immune glomerular lesions by immunofluorescent study. No dense deposits were present on electronmicroscopic study. On serum examination, indirect immunofluorescent study showed perinuclear pattern antineutrophil cytoplasmic antibody (ANCA), but myeloperoxidase-ANCA and proteinase 3-ANCA were both negative. Her serum reacted only to azurocidin excluding other ANCA antigens: bactericidal permeability-increasing protein, cathepsin G, elastase, lactoferrin, or lysozyme. Serum creatinine level decreased, and C-reactive protein turned negative after steroid therapy. Azurocidin-ANCA also turned negative. It is suggested that azurocidin-ANCA might have been related to the inflammatory process of pauci-immune necrotizing crescentic glomerulonephritis in this patient.     

Thrombosis associated with cytomegalovirus infection in patients with ANCA-positive vasculitis

Three cases of venous thrombosis with pulmonary embolism in two patients associated with underlying antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis and reactivated cytomegalovirus (CMV) infection are described. In vitro studies previously have shown that infection of endothelium with CMV increases the release of procoagulant factors and stimulates the expression of adhesion molecules. Because the endothelial cell plays a pivotal role in maintaining the equilibrium between procoagulant and anticoagulant states, injury by ANCA-positive vasculitis and additional infection with CMV may ignite a local thrombosis easily. Although venous thrombosis is uncommon in CMV infection (eg, in the immunosuppressed state after organ transplantation), the combination of vasculitis and reactivated CMV infection may have contributed to injury of the vessel wall with subsequent development of thrombosis. A better awareness of this association could improve morbidity and may lead to prevention of potentially life-threatening pulmonary embolism. Patients with ANCA-positive vasculitis and CMV infection may profit from prophylactic anticoagulant therapy with heparin or low-molecular-weight heparin. © 2001 by the National Kidney Foundation, Inc.     

Anti-endothelial cell antibodies in antineutrophil cytoplasmic antibodies negative pauci-immune crescentic glomerulonephritis

Aim: Pauci‐immune crescentic glomerulonephritis (CrGN) is frequently associated with circulating anti‐neutrophil cytoplasmic antibodies (ANCA). However, in patients with ANCA‐negative pauci‐immune CrGN, the pathogenesis is not clear. Anti‐endothelial cell antibodies (AECA) have been implicated in the pathogenesis of vasculitis. The purpose of this study is to investigate the prevalence of AECA and their possible clinical significance in ANCA‐negative pauci‐immune CrGN. Methods: Sera from 19 patients with ANCA‐negative pauci‐immune CrGN, 26 patients with ANCA‐positive pauci‐immune CrGN and 10 healthy blood donors were collected. Soluble proteins extracted from cultured human umbilical vein endothelial cells were used as antigens and western blot analysis was carried out to detect AECA. Results: In ANCA‐negative pauci‐immune CrGN, 10 of 19 patients were serum IgG‐AECA positive and seven bands reactive with endothelial antigens could be blotted. The prevalence of skin rash and thrombocytosis was significantly higher in patients with anti‐76 kDa and anti‐123 kDa autoantibodies than in patients without, respectively. Birmingham Vasculitis Activity Scores of patients with anti‐200 kDa AECA were significantly higher than in patients without. In the sera of 26 ANCA‐positive cases, 23 were AECA positive and 11 bands could be recognized. The prevalence of total AECA and anti‐90 kDa AECA was significantly lower in patients with ANCA‐negative pauci‐immune CrGN than in patients with ANCA‐positive pauci‐immune CrGN. Conclusion: Anti‐endothelial cell antibodies could be found in sera of patients with ANCA‐negative pauci‐immune CrGN; some AECA might have some clinical significance. The discrepancies of AECA might be a possible contributor to the differences between ANCA‐negative and ANCA‐positive pauci‐immune CrGN.     

Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis associated with rheumatoid arthritis: An unusual case report

Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.     

Anti-neutrophil cytoplasmic antibody associated glomerulonephritis in a patient with Down's syndrome

A 9-year-old boy with Down's syndrome developed a glomerulonephritis associated with crescents and anti-neutrophil cytoplasmic antibodies (ANCA). The patient also had type 1 diabetes mellitus, chronic lymphocytic thyroiditis, and bronchial asthma. Prednisone therapy resulted in an improvement in renal function and a reduction in ANCA titers.     

Cryptococcosis associated with crescentic glomerulonephritis

Crescentic glomerulonephritis (CGN) is an uncommon form of renal injury in childhood. Whereas many infectious processes are known to be linked to CGN, fungal infections typically are not. This report describes an 11-year-old girl who presented with CGN, cutaneous anergy, and cryptococcal mediastinitis. Whereas cryptococcal disease in children is usually associated with immunodeficiency (inherited or acquired), extensive immunologic evaluation of the patient was notable only for relative CD4 lymphopenia with normal CD4/CD8 ratios. Testing for human immunodeficiency virus was negative. Clinical and diagnostic studies are presented, along with a review of the literature regarding glomerular disease and cryptococcal infections.     

Antineutrophil cytoplasmic antibody-associated glomerulonephritis in Taiwanese

AIMS: This retrospective study defined the clinical features and outcome of antineutrophil cytoplasmic antibody-associated glomerulonephritis in 18 seropositive Taiwanese patients (11 male, seven female; median age 64 years; range 21-82 years) with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis. RESULTS: Fourteen patients had a diagnosis of systemic vasculitis including 10 with microscopic polyangiitis and four with Wegener's granulomatosis; the remaining four had only glomerulonephritis. At onset, 100% of the systemic vasculitis patients had pulmonary lesions with or without haemoptysis, and 29% presented with seizure in the absence of a defined brain lesion. Median serum creatinine concentration was 362.4 micromol/L (range 61.9-857.5 micromol/L) and dialysis therapy was needed in six patients. During follow up (median 16.5 months; range 2-72 months), treatment included cyclophosphamide and corticosteroids (n = 8) or corticosteroids alone (n = 7). In some patients, treatment improved (n = 4) or stabilized (n = 4) renal function. But chronic dialysis was needed in the other 10 patients. Follow-up death occurred because of sepsis (n = 3) and haemorrhage (n = 2). Patient survival rates were 78% (1 year) and 72% (5 years). Renal survival rates were 56 and 39% at 1 and 5 years, respectively. Of the candidate clinical and pathological parameters, chronic glomerular lesions in renal biopsy were the only determinant of poor renal outcome (P = 0.006). CONCLUSION: Antineutrophil cytoplasmic antibody-associated glomerulonephritis should be considered in nephritic patients with extrarenal manifestations, especially pulmonary infiltrate, unexplained seizure, and fever of an unknown origin in Taiwanese patients. Renal biopsy should be performed before initiating immunosuppressive therapy because the most common cause of mortality was sepsis.     

Enterococcal endocarditis associated with crescentic glomerulonephritis

Glomerulonephritis secondary to infective endocarditis (IE) is an uncommon diagnosis and is usually associated with cardiac valvular infection by blood-culture-positive bacteria. We report a case of necrotizing glomerulonephritis associated with culture-positive endocarditis caused by Enterococcus faecalis. The patient presented with renal abnormalities and was further investigated by renal biopsy. He had immune complex-mediated necrotizing and crescentic glomerulonephritis with mesengial and capillary deposition of immunoglobulin M (Ig M), Ig G, and complement 3 (C3). He was treated with antibiotics, including ampicillin and gentamicin. In addition, steroid and cyclophosphamide were administered. The patient died of renal failure 48 days after hospital admission. In conclusion, glomerulonephritis caused by Enterococcus faecalis endocarditis is an immune-complex-mediated disease characterized by necrotizing and crescentic glomerular lesions that can be fatal despite aggressive antimicrobial and immunosuppressive therapy.     

100例新月体肾炎的免疫病理分型及临床病理分析

目的：了解新月体性肾炎的免疫病理分型及其临床病理特点。方法：对我科近10年来经肾活检确诊的100例新月体性肾炎进行回顾性分析,对患者血清进行抗中性粒细胞胞浆抗体（ANCA）和抗肾小球基底膜（GBM）抗体的检测。结果：100例患者中21％为抗GBM抗体型,其中6／21例同时合并ANCA阳性;47％为免疫复合物型,其中9／47型ANCA阳性;32％为少免疫沉积型,其中17／32例为ANCA阳性小血管炎。3种类型相比,抗GBM抗体型以青年男性为主,多有少尿或无尿（P＜0．05）,肾小球受累受为广泛（P＜0．001）,预后差（P＜0．001）。免疫复合物型以中青年为主,多表现为肾病综合征（P＜0．01）,强化免疫抑制治疗有效。少免疫沉积型以中老年为主,有多系统受累（P＜0．05）,治疗效果相对较好。结论：我国新月体肾炎中虽仍以免疫复合物型为主,但抗GBM抗体型和ANCA阳性小血管炎并不少见。肾活检免疫病理和血清自身抗体的联合应用对新月体肾炎进行分类更接近病因学诊断。     

Transformation from Tubulointerstitial Nephritis to Crescentic Glomerulonephritis: An Unusual Presentation of ANCA-Associated Renal Vasculitis

A 44-year-old man with acute renal failure and antineutrophil cytoplasmic antibodies (ANCA) positivity was described. The first renal biopsy specimen showed tubulointerstitial nephritis (TIN) with normal glomeruli. However, delayed recovery of renal function with low-dose steroid treatment for TIN prompted a second renal biopsy 1 month later; and the specimen demonstrated a dramatically different morphology, with necrotizing and crescentic glomerulonephritis. Improvement in renal function occurred, together with reduction of ANCA titers, following intensive immunosuppressive therapy. This case illustrates an unusual presentation of TIN in ANCA-associated renal vasculitis. The possible pathogenetic mechanism are discussed.     

Anti-neutrophil cytoplasmic autoantibodies in a child with pauci-immune necrotizing and crescentic glomerulonephritis

We report a case of pauci-immune, necrotizing and crescentic glomerulonephritis in a 10-year-old child initially thought to have Henoch-Schönlein purpura. The diagnosis of a Wegener's granulomatosis-microscopic polyarteritis disorder was made on the basis of clinical presentation and a positive anti-neutrophil cytoplasmic auto-antibody (ANCA). This case illustrates the usefulness of the ANCA in the diagnosis and management of childhood vasculitides.     

ANCA-negative pauci-immune crescentic glomerulonephritis complicated with recurrent massive gastrointestinal hemorrhage

On April 25, 2003, a 62-year-old Japanese man had been admitted to a hospital because of heavy proteinuria and elevated serum creatinine level, and purpura on the lower extremities. On May 15, 2003, he was referred to our hospital for evaluation and treatment. Serum immunoglobulin and complements were within normal ranges. Immune serology was negative for antinuclear antibody, antiglomerular basement membrane antibody, and antineutrophil cytoplasmic antibodies. Histological examination of a percutaneous renal biopsy specimen revealed that all of the glomeruli had severe crescent formation without deposits of immunoreactants. A diagnosis of antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis was made. The patient was treated with one cycle of steroid pulse therapy (1000 mg methylprednisolone daily, given on 3 consecutive days), and subsequently with prednisolone (60 mg/day). Despite this treatment, renal failure progressed rapidly and hemodialysis was started 1 month after the acute presentation. On May 30, 2003, he suddenly developed massive hematochezia. A technetium-targeted red-blood-cell scan suggested bleeding in the small intestine. On June 11, he presented with massive melena. A bleeding ulcer was found in the third part of the duodenum, and was treated successfully with endoscopy, using a heater probe. On June 19, he presented with massive hematochezia again. Mesenteric angiography revealed active bleeding from the iliac branch of the superior mesenteric artery. He was treated with continuous intraarterial vasopressin infusion by a catheter seated in the branch artery. The majority of patients with pauci-immune crescentic glomerulonephritis, one of the most common causes of rapidly progressive glomerulonephritis, have glomerular disease as part of a systemic vasculitis. Massive gastrointestinal bleeding, although rare, should be considered one of the serious complications in these patients.     

Crescentic glomerulonephritis: new aspects of pathogenesis

This review provides a summary of recent advances in the understanding of crescentic glomerulonephritis, focusing on antineutrophil cytoplasm antibody (ANCA)-associated vasculitis and anti–glomerular basement membrane (anti-GBM) antibody disease. In ANCA-associated vasculitis (AAV), four main conceptual advances are discussed as follows: (1) evidence for the pathogenicity of ANCA, (2) molecular mimicry and the role of infection in AAV, (3) evidence for aberrant T-cell responses and T-cell regulation in AAV, and (4) advances in understanding of genetic predisposition to AAV. In relation to anti-GBM disease we discuss the following: (1) the nature of the Goodpasture autoantigens, (2) T-cell responses and regulation in anti-GBM disease, and (3) human leukocyte antigen and non–human leukocyte antigen genetic associations.     

Antineutrophil cytoplasmic antibody-positive rapidly progressive glomerulonephritis caused by propylthiouracil: A case report

Propylthiouracil, which is used as an antithyroid drug, is associated with many side effects. Vasculitis is a rare complication of this drug. Recently, antineutrophil cytoplasmic antibodies (ANCA) have been described in association with vasculitic disorders, including rapidly progressive glomerulo-nephritis. We report a case of ANCA-positive rapidly progressive glomerulonephritis caused by propylthiouracil administration. Although renal function was improved by discontinuation of the drug and initiation of steroid therapy, assay results for ANCA to myeloperoxidase remained positive throughout the clinical period.     

ANCA-associated glomerulonephritis in systemic-onset juvenile idiopathic arthritis

Systemic-onset juvenile idiopathic arthritis is an inflammatory disease of unknown cause and is not commonly associated with kidney involvement. We describe 3 patients with systemic-onset juvenile idiopathic arthritis with high disease activity who developed antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis 1-6 years after the onset of systemic-onset juvenile idiopathic arthritis. Renal and systemic-onset juvenile idiopathic arthritis remission occurred in one patient under anti-interleukin 1 (anti-IL-1) treatment associated with immunosuppressive drugs. The other 2 patients developed end-stage renal disease, and one of those patients died. This report suggests that the diagnosis of ANCA-associated glomerulonephritis must be considered in patients with systemic-onset juvenile idiopathic arthritis with persistently active systemic disease who present with proteinuria. Furthermore, use of an anti-IL-1 agent might be an effective therapeutic option.     

The clinical and pathological characteristics of Chinese patients with pauci‐immune crescentic glomerulonephritis

SUMMARY In the present study, we investigated pauci‐immune crescentic glomerulonephritis (PICGN) in Chinese patients. During 13 years (1985–98), 6400 patients underwent non‐transplanting renal biopsy in the Nanjing Jinling Hospital. Twenty‐four patients were diagnosed as having PICGN. They were 16 women and eight men with a median age of 33 (range 10–76 years). Microscopic polyarteritis (33.3%) and polyarteritis nodosa (8.3%) were the secondary diseases. The incidence of PICGN was 0.37% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. Onset gross haematuria was noted in 58.3% of the patients, hypertension 45.8%, nephrotic syndrome 41.7%, and oliguria 25.0%. However, systemic symptoms were rare except anaemia. Pathologically, we observed necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in interstitium (53.3%), in addition to glomerulosclerosis more than 50% (45.8%), severe tubular atrophy (83.3%) and interstitial fibrosis (75.0%). Antineutrophil cytoplasmic antibodies were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were subjected to long‐term follow up (median 29.8, range 8–92 months), 12 of them had life‐sustaining renal function, four had normal range of serum creatinine (< 124 μmol/L), only four patients were dialysis dependent.     

Impact of clinical and histopathological factors on outcome of egyptian patients with crescentic glomerulonephritis

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.     

Hemorrhagic complications associated with PR3-ANCA crescentic glomerulonephritis

Abstract

Hemorrhagic complications of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis are life-threatening conditions. Of these, alveolar hemorrhage is the most common and well-described hemorrhagic complication and is a prominent component of the pulmonary-renal syndrome. The clinical presentation of alveolar hemorrhage is highly variable ranging from mild to serious disease that may require respiratory support. Less attention has been directed at hemorrhagic complications that have been reported in other organs and which may be as severe or more severe with regard to morbidity and mortality. For example, among the most serious non-pulmonary complications are those related to cerebral and gastrointestinal hemorrhage. Cerebral hemorrhage is the clearly the most critical issue with a persistent high mortality rate. The prognosis of gastrointestinal hemorrhage, once an ominous complication has improved with medical and surgical intervention. Not to be dismissed are the consequences of hemorrhagic issues related to skin, soft tissue or muscle involvement. Muscle hematomas, while rare, also accompanied by significant morbidity.     

骨调素对巨噬细胞在新月体肾炎肾脏组织局部浸润的影响

目的观察骨调素（ＯＰＮ）在大鼠实验性新月体肾炎肾脏组织中的表达及功能性抑制ＯＰＮ的活性对巨噬细胞在肾脏局部浸润的影响。方法ＯＰＮ在肾脏组织蛋白和基因水平的表达分别应用免疫组化双标记及原位杂交技术。结果在实验性新月体肾炎肾脏组织内ＯＰＮ的表达明显升高，并与肾脏局部巨噬细胞的浸润、肾脏病理损害程度及肾功能的下降明显相关。应用抗ＯＰＮ抗体治疗以后可显著抑制ＯＰＮ在肾脏组织的表达，同时巨噬细胞在肾脏组织局部的浸润也明显减少，肾脏病理损害减轻、肾功能明显改善。结论ＯＰＮ的高表达是实验性新月体肾炎发病过程中巨噬细胞在肾脏组织局部浸润的重要介导因子，抑制ＯＰＮ的表达和功能可显著抑制肾脏局部巨噬细胞的聚集及改善肾功能。