Crescentic glomerulonephritis associated with infective endocarditis: renal recovery after immediate surgical intervention

A 57-year-old man was referred to our hospital because of acute cardiac failure and acute renal insufficiency. Laboratory data showed elevation of serum immune complex levels and antineutrophil cytoplasmic antibody (ANCA) titers, with cytoplasmic pattern (C-ANCA) on indirect immunofluorescence (IIF), and proteinase 3 specificity (PR3-ANCA) on solid-phase enzyme-linked immunosorbent assay (ELISA). Hemodialysis therapy was initiated, and this relieved the symptoms of cardiac failure. Echocardiography revealed three-grade aortic insufficiency and two large floating vegetations on the aortic valve. Considering the risk of embolism, we immediately performed aortic valve replacement and surgically removed the vegetations, subsequently giving antibiotic therapy. Six weeks after the operation, the patient's renal function showed marked improvement and the serological abnormalities, except for ANCA titers, had normalized, resulting in no need for dialysis. A renal biopsy specimen revealed diffuse proliferative glomerulonephritis (GN) with crescents including more than 50% of glomeruli, and granular deposits of IgM, C3, and C1q on immunofluorescence. ANCA titers remained high, but the patient's renal function has been stable, indicating a discrepancy between ANCA titers and his clinical course. In this patient, treatment by immediate surgical intervention, performed during the acute phase with active GN and highly reduced renal function, led to dramatic renal recovery. This case suggests that surgical removal of vegetations in the early stage of crescentic GN may result in a good renal outcome in patients with rapidly progressive GN associated with endocarditis. Although it has been suggested that ANCA may have some relationship to GN in endocarditis, in this patient, its pathogenetic significance is questionable. Received: March 10, 2000 / Accepted: May 23, 2000     

Renal transplantation in a C-ANCA(+) patient with Behcet disease and rapidly progressive glomerulonephritis

Behcet's disease (BD) is a chronic, relapsing, inflammatory disorder, and the underlying histophatological lesion is vasculitis of unknown cause. Some case reports of BD with positive C-ANCA titers have been reported, but only 2 case reports have documented the association of ANCA-associated glomerulonephritis (GN) and BD, and no renal transplantation cases have been described. We report such a case. A 27-year-old male was referred for consultation due to acute renal failure. Seven years before, BD was diagnosed. At the time of consultation he suffered from uveitis and generalized arthralgias. The serum creatinine was 14 mg/dl and urinalysis showed 4+ protein and microscopic hematuria. Results of serological tests were normal. The ANCA PR 3 titer was 1:100 of cytoplasmic pattern. A renal biopsy showed a rapidly progressive type III glomerulonephritis. In spite of immunosuppressive therapy with cyclophosphamide and high steroid doses, renal function did not recover and hemodialysis therapy was initiated. One year later, the patient underwent a renal transplantation. Follow-up was absolutely normal, and 5 years after transplantation, renal function persisted to be normal, without urinary abnormalities and signs of reactivation of original disease, except for occasional arthralgias. C-ANCA titer was decreased and remained stable (<1:30). He is now receiving maintenance immunosupression with cyclosporin and prednisone. This report shows the long-term successful renal transplantation in a patient with ANCA-associated glomerulonephritis and BD. The success of renal transplant in BD with renal involvement is encouraging and should be pursued.     

Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM crescentic glomerulonephritis

OBJECTIVE: To study the prevalence of ANCA and their target antigen in Chinese patients with anti-GBM crescentic glomerulonephritis (CGN), and to evaluate the possible role of ANCA in Chinese anti-GBM CGN patients with coexisting serum ANCA by studying clinicopathologic features of this disease. MATERIAL AND METHODS: Twenty-three sera were collected from 23 renal biopsy-proven anti-GBM CGN patients. According to the standardized procedures, all of the sera were determined by both, indirect immunofluorescence (IIF) ANCA, and enzyme-linked immunosorbent assay (ELISA) MPO-ANCA, PR3-ANCA and BPI-ANCA. The patients were divided into two groups according to serum ANCA positivity (Group A) or negativity (Group B). Thirty-three ANCA-associated pauci-immune CGN patients were regarded as control group (Group C). Their clinicopathologic features were compared to reveal whether ANCA correlated with disease activity. RESULTS: There were 11 (47.8%) cases with positive serum ANCA in 23 anti-GBM glomerulonephritis patients. There were 4/11 MPO-ANCA (one with positive PR3-ANCA and C-ANCA, three with negative IIF-ANCA), 1/11 PR3-ANCA (with positive MPO-ANCA and C-ANCA), 3/11 P-ANCA (with negative ELISA-ANCA) and 5/11 C-ANCA (one with positive PR3-ANCA and MPO-ANCA, and the other four with negative ELISA-ANCA). No BPI-ANCA was detected. No different clinicopathologic features were found between Groups A and B. Both were different from Group C in age, sex ratio, frequence of anuria and ESRD, variety of crescents, glomerular sclerosis, vessel lesion and prognosis. CONCLUSION: Our data demonstrate that ANCA in Chinese patients with anti-GBM CGN is not rare. The major target antigen of ANCA is MPO. ANCA seems not to be correlated with disease activity.     

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.     

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.     

Clinical investigation of anti-myeloperoxidase antibodies in patients with glomerulonephritis with crescent formation

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.     

Antineutrophil cytoplasmic autoantibodies and associated diseases: a review

Antineutrophil cytoplasmic autoantibodies (ANCA) are specific for constituents of neutrophil primary granules and monocyte lysosomes. There are different types of ANCA with different specificities. By indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate, two major categories of ANCA can be recognized, one with cytoplasmic staining (C-ANCA) and the other with artifactual perinuclear staining (P-ANCA). Some C-ANCA have specificity for proteinase 3 (PR3-ANCA) and some P-ANCA have specificity for myeloperoxidase (MPO-ANCA), but there are additional C-ANCA and P-ANCA specificities. ANCA are found in the blood of patients with necrotizing systemic vasculitis, such as Wegener's granulomatosis and polyarteritis nodosa, and patients with idiopathic crescentic glomerulonephritis. The glomerular lesion in patients with systemic and renal-limited ANCA-associated diseases is the same, ie, a pauci-immune necrotizing and crescentic glomerulonephritis. No matter where the vascular lesions of ANCA-associated disease are (eg, kidney, lung, gut, muscle, skin), they are characterized by necrotizing inflammation and a paucity of immune deposits. The distribution of disease correlates to a degree with the ANCA specificity, although there is substantial overlap. For example, patients with Wegener's granulomatosis most often have C-ANCA and patients with renal-limited disease most often have P-ANCA. In patients with P-ANCA-associated glomerulonephritis, approximately 90% of the P-ANCA have specificity for MPO. The clinical manifestations of ANCA-associated diseases often begin following a flu-like illness. The onset is most often in the winter and least often in the summer. The renal disease usually presents as rapidly progressive renal failure with nephritis. One of the most life-threatening components of the systemic involvement is pulmonary hemorrhage caused by a necrotizing alveolar capillaritis. Intravenous cyclophosphamide plus steroids is as effective as oral cyclophosphamide plus steroids for controlling ANCA-associated diseases. Using life-table analysis, the 2-year patient and renal survival rate in both patients with renal-limited and systemic disease is greater than 70%. There is evidence that in addition to being a useful serologic marker, ANCA are directly involved in the pathogenesis of the vascular injury in patients with ANCA-associated diseases. Although ANCA antigens are normally in the cytoplasm of neutrophils and monocytes, priming of these cells, as occurs following exposure to certain cytokines, results in the release of small amounts of ANCA antigens at the cell surface. In vitro, ANCA-IgG causes cytokine-primed neutrophils to undergo a respiratory burst and degranulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been identified as a diagnostic marker in primary systemic vasculitis, and immunofluorescence assays identify two patterns of binding: cytoplasmic (C-ANCA and perinuclear (P-ANCA). We have examined retrospectively the use of such assays in long-term monitoring of disease activity, in order to determine the relationship between presence of ANCA and relapse, and to assess their suitability as a guide to therapy. Seventy patients were studied over a period of 50 months, using clinical and laboratory criteria for the diagnosis of relapse and the internationally standardised immunofluorescence assay for detection of ANCA. In 19 patients C- or P-ANCA were detectable throughout the study period; six of these (with C-ANCA) relapsed. In 18 patients ANCA were undetectable during long-term follow-up; none of these patients relapsed. In 33 patients C- or P-ANCA were intermittently present; nine of these relapsed and all had C-ANCA detectable at the time of relapse. In six of the nine cases, relapse was accompanied or closely preceded by reappearance of C-ANCA. We conclude that continuing presence and reappearance of ANCA may identify patients who are at risk of relapse and who are most likely to benefit from long-term immunosuppressive therapy.     

De novo glomerulonephritis in patients during remission from Wegener's granulomatosis.

In a cohort of 20 consecutive patients with Wegener's granulomatosis and biopsy-proven pauci-immune crescentic glomerulonephritis three patients were in remission, but developed again a nephritic sediment without signs of systemic disease or positive ANCA titers. The second renal biopsy showed de novo mesangial IgA deposits 6, 17 and 28 months following admission for systemic disease and institution of immunosuppressive treatment. All patients were male, HLA-DR-2 positive and exhibited repeated upper respiratory tract infections. A fourth patient was admitted in end-stage renal failure with high titers of C-ANCA of the IgG isotype and proteinase 3 ab without clinical evidence of systemic manifestations of WG. Renal biopsy showed chronic sclerosing GN with marked IgA deposits. De novo development of IgA-GN is observed in a remarkable proportion of patients with WG and must be distinguished from exacerbation of the systemic disease.     

Cytoplasmic antineutrophil cytoplasmic antibody positive pauci-immune glomerulonephritis associated with infectious endocarditis

Renal deterioration often occurs in cases of infectious endocarditis (IE), but, IE- associated nephritis with rapidly progressive glomerulonephritis (RPGN) is rare. Patients with severe infection (e.g., IE) sometimes show positivity for cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA). Therefore, diagnosis and treatment are very difficult in cases of RPGN with IE and positivity for C-ANCA. Such cases are rare, only 12 have been reported in the English literature. Herein, we describe the case of a 50-year-old man who presented with RPGN with IE and tested positively for C-ANCA. He was referred to our hospital because of leg edema, purpura and renal dysfunction. Laboratory tests revealed serum creatinine elevation and positivity for C-ANCA and proteinase 3-specific (PR3)-ANCA. RPGN and acute renal failure were diagnosed. Hemodialysis and steroid therapy were started. Streptococcus oralis was isolated by blood culture. Transthoracic echocardiography revealed grade III mitral valve insufficiency with two vegetations. Therefore, IE was diagnosed. The steroid therapy was stopped, and antibiotic therapy was begun. Because there was no improvement, surgical therapy was performed. The operation was successful, but the patient died of brain hemorrhage. Our experience in this case indicates C/PR3-ANCA positive RPGN must be ruled out in patients with infectious disease, particularly IE, together with renal symptoms, and renal biopsy should be performed.     

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.     

Two cases of ANCA-associated vasculitis in post-transplant kidney: relapse and de novo

Abstract:  Two cases of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (ANCA-V) occurred in the transplanted kidney were reported. Case 1 was a 57 yr-old female whose original disease was MPO-ANCA-V. A relapse of necrotizing crescentic glomerulonephritis occurred one year after transplantation with positive serum reaction for MPO-ANCA. In spite of several immunosuppressive treatments, the disease progressed and she returned to hemodialysis treatment three yr and seven months after transplantation. Case 2 was a 34 yr-old female whose original disease was IgA nephropathy. She had a stable clinical condition during 13 yr after transplantation; however, de novo onset of necrotizing crescentic glomerulonephritis occurred at 14 yr 10 months after transplantation with positive serum reaction for MPO-ANCA. She returned to hemodialysis treatment five yr after the onset of ANCA-V. Urinary abnormities such as microhematuria and proteinuria were useful diagnostic findings but the titers of serum MPO-ANCA were relatively low in both patients. Concerning the treatment, steroid pulse therapy was effective in some extents but the disease progressed to graft failure in both cases. ANCA-V is a severe glomerulonephritis which can occur in kidney allograft in the manner of relapse and de novo . Detection of urinary abnormalities and positive serum ANCA combined with histological confirmation of necrotizing crescentic glomerulonephritis and/or vasculitis is required for early diagnosis and effective treatment of ANCA-V in renal transplant patients.     

Treatment of antineutrophil cytoplasmic autoantibody-positive systemic vasculitis and glomerulonephritis with pooled intravenous gammaglobulin.

Antineutrophil cytoplasmic autoantibody (ANCA) is considered a serological marker for disease activity in patients with ANCA(+) systemic vasculitis. Recently, ANCA has been implicated as a pathogenic antibody that may be associated with neutrophil degranulation and release of lytic enzymes. Since intravenous gammaglobulin (IVIG) is known to contain antiidiotypic antibodies to ANCA, which could decrease the activity of the later, we chose to treat two patients with symptomatic ANCA(+) systemic vasculitis and glomerulonephritis with high-dose IVIG. The first patient, a 66-year-old man, developed rapidly progressive renal failure despite treatment with intravenous (IV) cyclophosphamide. The second patient, a 14-year-old boy, had relapsed 3 months after cessation of treatment with prednisone and cyclophosphamide. Both patients improved dramatically after treatment with IVIG, with the former recovering renal function within 11 days of therapy. In both patients, a concomitant reduction in serum ANCA titers was also observed. The second patient is currently in a sustained remission 14 months after his last IVIG dose on no other medication. These cases provide clinical evidence that IVIG has therapeutic benefit in modifying the immune-mediated injury associated with ANCA(+) systemic vasculitis and glomerulonephritis. In addition, IVIG may provide an additional safe therapeutic option to clinicians treating patient's with ANCA(+) vasculitis and glomerulonephritis who are not responsive to or are experiencing toxicity from conventional therapy.     

A case of relapse of C-ANCA-associated glomerulonephritis in post-transplant patients

We experienced a case of relapse of proteinase 3-specific antineutrophil cytoplasmic autoantibody (C-ANCA)-associated rapid progressive glomerulonephritis (RPGN) in a patient after renal transplantation. A 19-yr-old man, who underwent a living donor kidney transplantation, presented a rapid renal function deterioration along with a sign of infection. Initially he was treated as acute rejection, but renal function did not improve. Renal biopsy revealed crescentic glomerulonephritis, and C-ANCA titer was 12 EU/mL, resulting in the diagnosis of C-ANCA-associated RPGN. He was treated with three consecutive methylprednisolone pulses twice in addition to the basal immunosuppressive medications (cyclosporine A and mizoribine), then his renal function improved to normal. Bearing the possibility of recurrence of glomerulonephritis in mind, we re-evaluated the nature and disease course of renal failure of original kidney. He experienced a rapid deterioration of renal function in 1992, and eventually CAPD was started in 1992. His serum in 1992 revealed high titer of C-ANCA (24 EU/mL), and renal biopsy performed in 1992 showed a crescentic glomerulonephritis. Taken together, we diagnosed this event as a relapse of C-ANCA-associated GN. Lessons from our experience are: 1) steroid pulse and high-dose corticosteroid therapy may be useful for the treatment of relapse of C-ANCA-associated GN patients after renal transplantation; 2) the possibility of a relapse of C-ANCA-associated GN following renal transplantation has to be kept in mind, especially when infection precedes the deterioration of allograft kidney function.     

Antineutrophil cytoplasmic autoantibody-associated glomerulonephritis in children.

Aretrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcome of antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in children. Thirty-four ANCA-seropositive Japanese pediatric patients with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis were identified. Of these, 3 cases associated with Wegener's granulomatosis were excluded because of the small sample size. Among the 31 patients studied, 10 had a diagnosis of necrotizing crescentic glomerulonephritis alone and 21 had microscopic polyangiitis. Females predominated (87%), and the median age at onset was 12 yr. Twenty-six patients received treatment with cyclophosphamide and corticosteroids, and five patients received treatment with corticosteroids alone; 84% of patients achieved remission, and 39% of responders relapsed in a median of 24 mo. ANCA titers correlated with response to treatment and disease activity, with some exceptions. Patients were followed for a median of 42 mo (range, 3 to 96 mo). Nine of 31 patients (29.0%) progressed to end-stage renal disease, 6 (19.4%) had reduced renal function, and 15 (48.4%) had normal renal function at the last observation. One patient (3.2%) died from cytomegalovirus infection 3 mo after initiation of therapy. Life-table analysis showed 75% renal survival at 39 mo. Patients who subsequently developed end-stage renal disease (n = 9) had significantly higher average peak serum creatinine levels and more chronic pathologic lesions at diagnosis compared with patients with favorable renal outcome (n = 15). In conclusion, our clinical experience suggests that the clinical disease spectrum of ANCA-associated glomerulonephritis is similar in pediatric and adult patients, but there is a female predominance in children.     

Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis

Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti-LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti-LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti-LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti-proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti-LAMP-2 titers, respectively. There was no correlation between anti-LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti-LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti-LAMP-2 antibodies and ANCA glomerulonephritis.     

The Diagnostic and Prognostic Significance of ANCA

Antineutrophil cytoplasmic antibodies (ANCA) constitute a family of autoantibodies directed against various components of the neutrophil cytoplasm. Their identification and association with vasculitis and rapidly progressive glomerulonephritis has led to considering these diseases as possible autoimmune disorders. In addition, ANCAs constitute a diagnostic tool and a guideline for therapy during follow-up. Originally identified by Davies et al. in 1982 in 8 patients who had necrotizing glomerulonephritis but no immune deposits or systemic vasculitis (1), ANCA are now regarded as a serological marker for active pauci-immune necrotizing and crescentic glomerulonephritis, either in their renal-limited form or associated with systemic vasculitis such as Wegener's granulomatosis (WG), microscopic polyangütis (mPA), and Churg-Strauss syndrome (CSS) (2-9). The usefulness of ANCA detection for the diagnosis of these forms of vasculitis is now established but its usefulness on follow-up remains disputed (10-13). Two major ANCA antigens have already been identified. Proteinase 3 (PR3) in a serine protease of 29 kDa initially identified by Kao and producing a cytoplasmic staining pattern termed cANCA by indirect immunofluorescence (IIF) (14,15). Myeloperoxidase (MPO) is another myeloid lysosomal enzyme producing an artefactual perinuclear staining of ethanol-fixed neutrophils termed pANCA (2,16). Both are localized in the azurophilic granules of neutrophils and monocytes, are translocated to the cell surface during cell activation (17), and are able to interact directly with ANCA. Despite this common location, MPO and PR3 are associated with a broad spectrum of clinical conditions.     

Analysis of clinical features and prognosis of anti-glomerular basement membrane antibody positive patients with anti-neutrophil cytoplasmic antibodies

Objective To investigate the characteristics and outcome of glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Methods The sera of 23 anti-GBM glomerulonephritis patients were collected and were tested for ANCA respectively. Characteristics and outcome of patients with coexisting anti-GBM antibody and ANCA were analyzed, and were compared with anti-GBM glomerulonephritis patients without coexisting ANCA. Results Among the 23 sera with anti-GBM antibody, 7 sera had coexisting ANCA (7 MPO-ANCA, 1 PR3-ANCA), which represented 30.4% of the anti-GBM glomerulonephritis patients. The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group was significantly higher than that in ANCA--anti-GBM glomerulonephritis group (P＜0.05). No significant difference in age, sex, other clinical manifestations and pathological features were found between patients with and without coexisting serum ANCA. Conclusion The incidence of hemoptysis and hematuria in ANCA+-anti-GBM glomerulonephritis group is significantly higher than that in ANCA--anti-GBM glomerulonephritis group, but the prognoses of the two groups were poor.     

A pediatric occurrence of crescentic glomerulonephritis associated with antineutrophil cytoplasmic antibodies and mesangial IgA deposits

Antineutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis usually shows histopathologic features of pauciimmune crescentic glomerulonephritis and occurs late in life. We report a 14-year-old Japanese girl presenting with proteinuria, hematuria and mildly elevated serum creatinine. A renal biopsy specimen demonstrated crescentic glomerulonephritis, immunofluorescence showed mesangial IgA staining. Electron microscopic examination disclosed paramesangial deposits. Serum ANCA against myeloperoxidase (MPO) were detected at high titers. Myeloperoxidase-ANCA-related nephritis accompanied by IgA nephropathy is considered rare in childhood and teen years. Yet, if ANCA assays and detailed electron microscopic examination of renal specimens were performed routinely in patients with rapidly progressive glomerulonephritis, the diagnosis might be more frequent in young patients.     

Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in collagen diseases associated with vasculitic syndrome in Japan.

The present study was undertaken to determine the anti-neutrophil cytoplasmic antibody (ANCA) levels in 96 patients with various collagen diseases associated with renal vasculitis and vasculitic syndrome in Japan. The results indicated that cytoplasmic(C)-ANCA is an autoantibody highly specific to Wegener's granulomatosis (WG) and that it is also active in renal injury. The relationships between ANCA and focal segmental necrotizing GN, i.e., renal vasculitis as proposed by Balow, were investigated. Perinuclear(P)-ANCA was detected with high sensitivity and specificity in renal vasculitis without WG, and the severity of necrotizing and crescentic nephritis in WG was correlated especially well with the C-ANCA titer. Detection of ANCA is considered clinically useful for the etiological differentiation of renal vasculitis, suggesting the possibility that C-ANCA may be involved in the onset of vasculitis of the glomerular capillary vessels in WG. The presence of C-ANCA and cytokines (IL-1 beta and TNF-alpha) is important in the pathogenesis of vasculitis and GN in WG.