Incidence and features of dual anti-GBM-positive and ANCA-positive patients

Aims: Goodpasture's syndrome, glomerulonephritis and pulmonary haemorrhage, may be due to a variety of causes. Rarely, patients with Goodpasture's syndrome present with both anti‐glomerular basement membrane (GBM) and antineutrophil cytoplasmic antibody (ANCA). The aim of this report was to determine the incidence, clinical features, management and outcomes of patients presenting with concurrent ANCA and anti‐GBM disease in Auckland. Methods: Potential patients were identified by an electronic search of serology for ANCA and anti‐GBM antibody, diagnostic renal biopsy, or in‐hospital admissions using ICD9 and ICD10 codes between 1998 and 2008. A retrospective case‐note review of all potential cases was performed. Results: Six cases were identified: two women and four men. The incidence was estimated at 0.47 cases per million people per year. The mean age of presentation was 59 years (range 25–85 years). One patient was a smoker and two patients were ex‐smokers. All subjects were anaemic, had haemoptysis and an abnormal chest X‐ray at presentation. The mean creatinine at presentation was 225 µmol/L (range 126–406 µmol/L); all patients had haematuria and proteinuria. All patients received corticosteroids and cyclophosphamide. Two patients were not plasma exchanged and died. Four patients received plasma exchange and are alive. One patient had a clinical relapse 6 years after their initial presentation and is on renal replacement therapy. Conclusion: Concurrent ANCA and anti‐GBM disease is rare. The mortality rate is high. Aggressive immunosuppression with steroids, cyclophosphamide and plasma exchange can induce remission and preserve renal function. Long‐term monitoring for relapses should occur.     

The Goodpasture antigen in Alport's syndrome: studies with a monoclonal antibody

A mouse monoclonal antibody (MCA-P1), which recognizes an antigenic determinant in human glomerular basement membrane against which autoantibodies are directed in Goodpasture's syndrome, was used in indirect immunofluorescence studies to investigate glomerular basement membrane structure in Alport's syndrome. We found reduced or absent binding of MCA-P1 to glomerular and distal tubular basement membranes in renal biopsy tissue from ten patients with Alport's syndrome. Antiglomerular basement membrane antibody eluted from the kidneys of a patient who had died from Goodpasture's syndrome was used to confirm these findings. In contrast, there was bright linear fluorescence of MCA-P1 on glomerular and tubular basement membranes of normal renal material and renal biopsy tissue obtained from patients with a variety of glomerulonephritides. These results suggest an abnormality or a variable quantity of the immunoreactive autoantigen in the glomerular basement membrane of patients with Alport's syndrome. Furthermore, MCA-P1 may be of value in the diagnostic interpretation of renal biopsies from patients with familial nephritis.     

IgA antiglomerular basement membrane disease associated with bronchial carcinoma and monoclonal gammopathy

Antiglomerular basement membrane (anti-GBM) disease is characterized by a linear deposition of immunoglobulins along the glomerular basement membrane. A 67-year-old man with a recently discovered monoclonal gammopathy of unknown significance (MGUS) presented with microscopic hematuria, nephrotic-range proteinuria, and rapidly deteriorating renal function after a pneumonia. Renal histology showed a crescentic glomerulonephritis; immunohistology showed intense linear staining of the GBM with immunoglobulin A (IgA) and moderate linear staining with kappa and lambda light chains. Screening for systemic disease, including diabetes mellitus, lupus erythematodes disseminatus, cryoglobulinemia, was negative. Serological tests for detection of anti-GBM antibodies were positive for IgA class and negative for IgG. Further examination indicated a bronchial carcinoma T2N2M0. This clinical report adds new information to the spectrum of anti-GBM disease and suggests that neoplasia may be associated with unusual exposure of and/or immune response to epitopes in the GBM.     

Linear glomerular IgG fixation in renal allografts: incidence and significance in Alport's syndrome

Twelve of 767 renal allograft recipients developed linear fixation of IgG along the glomerular basement membrane (GBM) by direct immunofluorescence technique. This was associated with linear fixation along the tubular basement membrane in 7 of them. Circulating anti-GBM antibodies were not detected by indirect immunofluorescence or radioimmunoassay in any patient whereas anti-TBM antibodies were found in 2 of 4 with linear TBM fixation. Among the 12 patients with linear GBM fixation, 5 had Alport's syndrome; the 7 others had various renal diseases, excluding anti-GBM nephritis. Among the 767 patients, 34 had Alport's syndrome or variants (i.e., 4.5%). The incidence of linear GBM fixation is much higher in Alport's syndrome than in other renal diseases. Linear GBM fixation was not clearly related to anti-GBM antibodies and was not accompanied by significant deterioration of graft function. These findings may be relevant, however, to the missing GBM antigen in Alport's syndrome.     

Circulating anti-glomerular basement membrane autoantibodies against α3(IV)NC1 undetectable by commercially available enzyme-linked immunosorbent assays

Aim: Cases with anti‐glomerular basement membrane (GBM) disease have been reported with linear deposit of immunoglobulin G (IgG) along GBM, but have undetectable anti‐GBM antibodies in circulation by enzyme linked immunosorbent assays (ELISA). We speculated that the structure of the antigens recognized by these antibodies may contribute to the negative results of ELISA. Methods: Sera from four patients were collected, with typical linear deposit of IgG along GBM but no anti‐GBM reactivity by commercial ELISA kits. Circulating anti‐GBM antibodies were detected by indirect immunofluorescence. Antigen specificity and its conformational structure was investigated by western‐blot analysis, using recombinant human α1–α5(IV)NC1 and chimeric proteins E_A and E_B as antigens. Results: The presence of circulating anti‐GBM antibodies were confirmed by indirect immunofluorescence with linear deposit of IgG towards cryptic epitopes along GBM on normal kidney sections. These antibodies did not recognize recombinant human α1, α2, α4 or α5(IV)NC1, but could blot α3(IV)NC1 under non‐reducing non‐boiling conditions on western‐blot analysis, when the conformational epitope(s) on α3(IV)NC1 were thought to be preserved. When α3(IV)NC1 was prepared under reducing conditions with β‐mercaptoethanol and/or boiled to destroy the disulfide bonds, the binding with the antibodies disappeared. Moreover, these antibodies recognized neither E_A nor E_B, indicating their distinct epitope repertoire. Conclusion: Circulating anti‐GBM antibodies undetectable by ELISA could recognize cryptic and conformation‐dependent epitopes restricted on α3(IV)NC1, distinct from E_A and E_B. Indirect immunofluorescence was necessary for antibody detection and treatment monitoring under such circumstances.     

Atypical antiglomerular basement membrane disease associated with thin membrane nephropathy

Antiglomerular basement membrane (anti-GBM) disease is characteristically described with linear deposition of IgG along the GBM. We report two unusual cases of IgA and IgM anti-GBM disease associated with diffuse thinning of the GMB, and review the literature on atypical immunoglobulin species in this disorder. Both patients were male, aged 55 and 49 years, and presented with isolated microscopic haematuria, neither having shown evidence of impaired renal or pulmonary function on follow-up for 4 and 6 years respectively. Renal histology revealed minor focal mesangial changes only, but immunoperoxidase preparations demonstrated intense linear staining of the GBM with IgA in one case, and IgM with C3 in the other. On electron-microscopy there was diffuse thinning of the GBM in both cases, mean thickness 220 and 295 nm respectively (normal range 350-450 nm). Antinuclear antibodies were not detected and their glucose tolerance tests were normal. Assays for circulating IgG anti-GBM antibodies using indirect immunofluorescence (IF) and radioimmunoassay (RIA) were negative in both patients, although IgA anti-GBM antibodies with specificity confirmed by inhibition studies were identified in the first case. Thin GBMs in these patients may expose the Goodpasture antigen to toxic or infectious insults, thus altering its antigenic profile and promoting this unusual immune response.     

抗肾小球基底膜抗体伴抗中性粒细胞胞浆抗体阳性肾炎(四例报告及文献复习)

目的　了解抗肾小球基底膜抗体（ Ａｎｔｉ Ｇ Ｂ Ｍ） 伴抗中性粒细胞胞浆抗体（ Ａ Ｎ Ｃ Ａ） 阳性患者的临床病理特点。方法　对我科近４ 年来６８ 例 Ａｎｔｉ Ｇ Ｂ Ｍ 和（ 或） Ａ Ｎ Ｃ Ａ 阳性患者进行 Ａｎｔｉ Ｇ Ｂ Ｍ 及 Ａ Ｎ Ｃ Ａ 检测,对其中４ 例两者均阳性患者进行临床病理分析。结果　６８ 例患者中４ 例两者均阳性,占全部 Ａｎｔｉ Ｇ Ｂ Ｍ 阳性患者的２４ ％ ,占全部 Ａ Ｎ Ｃ Ａ 阳性患者的７ ％ 。该４ 例患者 Ａｎｔｉ Ｇ Ｂ Ｍ 的百分结合率较单纯 Ａｎｔｉ Ｇ Ｂ Ｍ 阳性患者低。４ 例中３ 例髓过氧化物酶 Ａ Ｎ Ｃ Ａ（ Ｍ Ｐ Ｏ Ａ Ｎ Ｃ Ａ） 阳性,１ 例蛋白酶３ Ａ Ｎ Ｃ Ａ（ Ｐ Ｒ３ Ａ Ｎ Ｃ Ａ） 阳性,全身系统表现较多,与单纯性 Ａ Ｎ Ｃ Ａ 阳性患者相似。所检病例肾脏病理多为新月体肾炎,免疫荧光检查多为 Ｉｇ Ｇ、 Ｃ３ 呈细颗粒样分布于 Ｇ Ｂ Ｍ。虽经积极治疗,多数患者预后较差,类似单纯 Ａｎｔｉ Ｇ Ｂ Ｍ 肾炎。结论　 Ａｎｔｉ Ｇ Ｂ Ｍ 伴 Ａ Ｎ Ｃ Ａ 阳性患者全身表现类似单纯 Ａ Ｎ Ｃ Ａ 相关小血管炎患者,但治疗效果及预后相对较差又类似于 Ａｎｔｉ Ｇ Ｂ Ｍ 肾炎患者     

Childhood thin GBM disease: review of 22 children with family studies and long-term follow-up

Thin glomerular basement membrane (GBM) disease is generally known to have a good renal prognosis, although renal insufficiency has sometimes been reported and the overlap with Alport syndrome implies that a good prognosis cannot be guaranteed. In order to shed light on long-term prognosis of thin GBM disease we have retrospectively evaluated 22 children with persistent haematuria and biopsy-proven thin GBM. Mean follow up was 7 years (range 2–17 years), mean age at onset was 7 years (range 1.5–15). Biopsies were performed a mean of 3.8 years after detection of hematuria. The light microscopy (LM) and immunofluorescence (IF) findings were essentially unremarkable in all of the children, while electron microscopy (EM) showed thinning of the GBM in all cases and no changes characteristic of Alport syndrome. The family history was positive for renal disease in 17 (77.3%) patients with hematuria in 8 (36.3%) families, and hematuria with renal failure (RF) or deafness in 9 (40.9%). It was completely negative for renal disease in 4 (18.2%) and unavailable in 1 (4.5%). Four patients (18%) showed a decline in renal function after 6, 8, 9 and 12 years of follow-up, and 1 of these also developed hearing impairment. None developed hypertension.Our study suggests that thin GBM disease is not always benign and a child with thin GBM should never be assigned such a prognosis, especially if there is a family history of renal impairment or deafness, where careful follow-up is needed due to the risk of late onset renal failure.     

Injured kidney cells express SM22α (transgelin): Unique features distinct from α-smooth muscle actin (αSMA)

Aim: SM22α (transgelin) has been focused upon as a player in the process of phenotypic changes of types of cells. The SM22α expression in the rat anti‐glomerular basement membrane (GBM) nephritis model and differences from an established phenotypic marker for the myofibroblast, α‐smooth muscle actin (αSMA), were investigated. Methods: The rat kidney tissues were processed for histological studies, immunohistochemical and immunoelectronmicroscopy analyses on days 0, 7, 28, 42 and 56 after injection of rabbit anti‐GBM serum for the disease induction. Results: Immunohistochemistry with anti‐SM22α antibodies (Ab) revealed that kidneys of the nephritic rats on day 7 expressed SM22α in podocytes, crescentic cells and epithelial cells of Bowman's capsule. After 28 days, SM22α was also expressed in peritubular interstitial cells. Double immunofluorescence with anti‐SM22α Ab and anti‐αSMA Ab showed that SM22α was preferentially expressed in podocytes, whereas αSMA was positive in mesangial cells on day 7. After day 28, both molecules became positive in peritubular interstitial cells. Conclusion: SM22α was expressed in epithelial cells of inflamed glomeruli in the early phase, and then also in peritubular interstitial cells in the later phase of anti‐GBM nephritis model. SM22α presented unique kinetics of expression distinct from αSMA.     

Allograft rejection and glomerular basement membrane antibodies in Alport's syndrome

BACKGROUND: Anti-glomerular basement membrane (GBM) antibodies occasionally occur in Alport patients after renal allograft transplantation. METHODS: We report a patient with Alport's syndrome who lost four transplants each within the first year post transplantation. We searched for the presence of anti-GBM antibodies using recombinant NC1 domains of type IV collagen. Immunoblotting, enzyme linked immunosorbent assay (ELISA), and immunofluorescence were used to detect the presence of antibodies against the glomerular basement membrane. RESULTS: High antibody titers to the alpha3 chain (the Goodpasture antigen) and alpha5 chain of type IV collagen were detected. Review of pathologic specimens showed features of vascular rejection in all specimens. CONCLUSION: The association of high titer anti-GBM antibodies and vascular rejection may be important. When vascular rejection occurs in Alport patients, the presence of anti-GBM antibodies should be sought. Recombinant anti-GBM assays should be used if standard anti-GBM testing is equivocal.     

Concurrent Antiglomerular Basement Membrane Disease and Immune Complex Glomerulonephritis

Antiglomerular basement membrane (GBM) disease is characteristically described with linear deposition of IgG along GBM. However, the concurrent glomerular immune complex deposition was not rare and might be contributed to the development of anti-GBM disease. In the current series, glomerular immune complexes were identified in 10 of 47 patients who presented with renal-biopsy-proven anti-GBM disease. Six of the 10 patients complicated with a well-documented glomerulonephritis, including two patients with membranous nephropathy, one patient with IgA nephropathy, one patient with membranoproliferative glomerulonephritis, one patient with Schonlein–Henoch nephritis, and one patient with hepatitis B virus associated membranous nephritis. The other four patients had immune complexes with IgG or IgM predominance deposited in glomerular mesangium without a well-documented glomerulonephritis. Clinical and pathological data of patients with immune complex deposition (n = 10) were compared with those of patients with anti-GBM disease alone (n = 37). There was no significant difference in age, gender, clinical and pathological manifestations, and renal outcome between the two groups. In general, the association of glomerular immune complexes did not lead to a benign prognosis. Plasma exchange and extensive immunosuppressive therapy should be carried out as soon as possible. The immune complexes deposited in glomeruli might participate in the initiation of anti-GBM disease.     

肾组织中缺乏IgG线样沉积的抗肾小球基底膜病患者的临床病理特点

目的 研究肾组织中缺乏IgG沿肾小球毛细血管袢线样沉积的抗肾小球基底膜（GBM）病患者的临床、病理及预后特点。 方法 选取北京大学第一医院肾内科1991年至2008年确诊的抗GBM病患者93例,其中40例肾脏病理中冰冻切片直接免疫荧光检查缺乏IgG沿肾小球毛细血管袢沉积的患者为研究组（A组）,53例肾组织中有IgG沿肾小球毛细血管袢线样沉积的经典抗GBM病患者为对照组（B组）,比较两组患者的临床、病理和预后的差异。 结果 两组患者在性别、年龄、咯血、少尿或无尿和肉眼血尿的发生率、蛋白尿水平、贫血程度、循环中抗GBM抗体百分结合率、ANCA阳性率、肾脏病理肾小球中新月体的比例及组成成分、患者的生存率以及肾脏预后等方面,差异均无统计学意义（均P > 0.05）。肾组织中缺乏IgG沉积的患者,从起病到确诊所需的时间较长（68 d比36 d,P = 0.013）;确诊时的血肌酐水平较低（716.0 μmol/L比896.8 μmol/L,P = 0.027）。其中4例患者肾组织石蜡切片行直接免疫荧光检查可以见到IgG沿GBM呈线样沉积。 结论 肾脏病理冰冻切片直接免疫荧光缺乏IgG线样沉积的抗GBM病患者,与经典抗GBM病患者相比,肾脏病变进展较慢,但其他临床及病理表现并无显著差异,肾脏预后及患者存活率亦无显著差异。因此,临床上应尽早检测血清抗GBM抗体,早期给予血浆置换治疗,以改善预后。     

Concurrent antiglomerular basement membrane disease and immune complex glomerulonephritis

Antiglomerular basement membrane (GBM) disease is characteristically described with linear deposition of IgG along GBM. However, the concurrent glomerular immune complex deposition was not rare and might be contributed to the development of anti-GBM disease. In the current series, glomerular immune complexes were identified in 10 of 47 patients who presented with renal-biopsy-proven anti-GBM disease. Six of the 10 patients complicated with a well-documented glomerulonephritis, including two patients with membranous nephropathy, one patient with IgA nephropathy, one patient with membranoproliferative glomerulonephritis, one patient with Schonlein-Henoch nephritis, and one patient with hepatitis B virus associated membranous nephritis. The other four patients had immune complexes with IgG or IgM predominance deposited in glomerular mesangium without a well-documented glomerulonephritis. Clinical and pathological data of patients with immune complex deposition (n = 10) were compared with those of patients with anti-GBM disease alone (n = 37). There was no significant difference in age, gender, clinical and pathological manifestations, and renal outcome between the two groups. In general, the association of glomerular immune complexes did not lead to a benign prognosis. Plasma exchange and extensive immunosuppressive therapy should be carried out as soon as possible. The immune complexes deposited in glomeruli might participate in the initiation of anti-GBM disease.     

Fibrillary glomerulonephritis presenting as rapidly progressive glomerulonephritis

Fibrillary glomerulonephritis (GN) is an uncommon cause of rapidly progressive kidney failure. We report a case of rapidly progressive kidney failure with kidney biopsy showing crescentic GN on light microscopy and immunofluorescence showing linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G and C3, consistent with anti-GBM disease. However, electron microscopy showed fibrillary deposits in the GBM, suggesting a diagnosis of fibrillary GN. As exemplified by this case, it is important to consider fibrillary GN in the differential diagnosis of crescentic GN with linear immunoglobulin G deposits within the GBM. Electron microscopy is crucial to make this diagnosis.     

Alport综合征患者肾组织层粘连蛋白α2链异常分布

目的 观察Alport综合征(AS)患者肾组织层粘连蛋白α2链、α5链和γ1链的分布。方法 采用免疫荧光方法,运用普通荧光和激光共聚焦扫描显微镜观察抗层粘连蛋白α2链、α5链和γ1链单克隆抗体在肾组织中的沉积情况。肾组织标本来自11例AS患者,其中男8例,女3例,年龄11~52岁。10例患者符合X伴性显性遗传(XLAS),1例女性患者符合显性遗传。8例男性XLAS患者肾小球基底膜(GBM)、远端肾小管基底膜均无Ⅳ型胶原α3、5链沉积,表皮基底膜(EBM)无α5(Ⅳ)链沉积;2例女性XLAS患者肾组织α3、5(Ⅳ)链和EBM α5(Ⅳ)链均呈不连续表达,另1例女性患者则同正常肾组织。正常人肾组织标本作为正常对照,9例IgA肾病(IgAN)、6例局灶节段硬化性肾小球病(FSGS)、5例薄基膜病(TBMD)和6例肾小球轻微病变(GML)患者作为疾病对照。结果 正常人肾组织层粘连蛋白α2链主要沉积于肾小球系膜区,层连蛋白α5、γ1链沉积于GBM、所有肾小管基底膜和入球小动脉基底膜。10例XLAS和1例显性遗传AS患者肾组织除了肾小球系膜区外,层粘连蛋白α2链在GBM上亦出现表达。IgAN、TBMD和FSGS患者层粘连蛋白α2链仅在肾小球系膜区沉积。层粘连蛋白α5、γ1链在AS患者和其他肾脏病组织沉积同正常肾组织。结论 层粘连蛋白α2链在AS患者GBM出现异位表达,为继Ⅳ型胶原α链异常之后发现的又一AS基底膜成分的异常,其对于AS可能具有重要的诊断价值。     

Outcome of thirty patients with Alport's syndrome after renal transplantation

Graft antiglomerular basement membrane nephritis in patients with Alport's syndrome (AS) is a unique complication related to the glomerular basement membrane (GBM) abnormality characteristic of the disease. Its prevalence and clinical significance however remain unknown. We used strict criteria of AS to select 30 patients (26 men, 4 women), aged 17 to 44 years (m: 27) in whom 35 grafts (30 first, 5 second) had been performed at our center between 1968 and 1988. Patient and graft survival were, respectively, 96 and 75% at 5 years, 77 and 42% at 10 years. Graft survival and function, as well as the incidence of rejection episodes in the AS group were not different from those of a control group without AS, matched for age, sex, graft origin, and immunosuppressive regimen. Fifteen grafts were examined by immunofluorescence at least 3 months after TP: linear IgG deposits along GBM were present in 5 cases in the absence of signs of crescentic glomerulonephritis. Circulating anti-GBM antibodies detected in one of these cases 8 months post-TP had disappeared 24 months later. The presence of linear IgG did not seem to influence graft survival and function. We conclude: (1) the overall outcome of TP in AS patients does not differ from a control group without AS; (2) appearance of linear glomerular IgG is frequent but is not necessarily associated with a poor graft outcome; (3) the course of de novo graft anti-GBM disease may be benign; and (4) the aggressivity of the disease could be determined by the degree of immunosuppression and/or by the specificity of the anti-GBM antibodies.     

成年人肾小球基底膜厚度及基底膜变薄标准研究

目的 了解成年人肾小球基底膜（GBM）厚度及拟建议薄基底膜肾病（TBMN）的GBM弥漫变薄的标准。 方法 选取肾癌根治性切除患者29例,分析性别、年龄、尿常规、Scr以及既往史、家族史等临床资料。选取远离病灶的肾皮质组织,进行光镜、免疫荧光及透射电镜检查,并进行GBM厚度测量和Ⅳ型胶原α3、α5链免疫荧光检查。 结果 29例中,男15例、女14例,年龄（55.9±14.9）岁（20~80岁）,所有病例均无肾脏病家族史。肾组织GBM厚度为（363.6±46.8） nm。GBM厚度与性别相关,男性为（384.0±41.7） nm,女性为（335.0±39.2） nm,差异有统计学意义（P = 0.008）。建议以均数减去两倍标准差作为GBM变薄的标准,即GBM厚度＜270 nm。 结论 成年人肾组织的GBM厚度为（363.6±46.8） nm。GBM厚度和性别相关,男性GBM厚度大于女性,差异有统计学意义。TBMN的GBM弥漫变薄的诊断标准建议为GBM厚度＜270 nm,也建议今后制定TBMN标准中应考虑男女的差异。     

A nephrotic case of vesicoureteral reflux representing focal segmental glomerulosclerosis associated with podocytic infolding lesions

The case was a 54-year-old woman who had suffered from occasional incontinence of urine after a craniotomy for subarachnoid hemorrhage in 1991. In June 1998 she was admitted for nephrotic syndrome without hematuria. Intravenous pyelography and voiding cystourethrography revealed bilateral hydronephrosis, atonic bladder, and vesicoureteral reflux (VUR). Renal biopsy demonstrated the presence of focal segmental glomerulosclerosis with cellular lesions. However, periodic-acid methenamine silver (PAM) staining revealed bubbling and spike appearance in the diffuse peripheral loops, although immunofluorescence microscopy showed negative findings in the glomeruli. Electron microscopy revealed diffuse thickening of the glomerular basement membrane (GBM) accompanying diffuse podocytic infolding lesions into the GBM and numerous spherical microstructures in the GBM. No findings of dense deposits were observed in the GBM and mesangium. Her urinary protein excretion decreased and renal function improved after placement of an urethral catheter for one year. A second renal biopsy revealed a remarkable decrease in podocytic infolding lesions, although microstructures in the GBM remained. Although mechanisms of the occurrence of these peculiar podocytic infolding lesions are unclear, it is speculated that podocyte damage due to hydronephrosis may have caused the lesions.     

Evolution of antiglomerular basement membrane glomerulonephritis into membranous glomerulonephritis

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare disease characterized by autoantibodies to the alpha 3 chain of type IV collagen in the GBM. It is also known as Goodpasture’s syndrome when associated with pulmonary hemorrhage due to autoantibodies to the alpha 3 chain of type IV collagen also present in pulmonary alveoli. Even more rare is the evolution of anti-GBM GN into membranous nephropathy (MN). We report the management of a 9-year-old Caucasian girl with anti-GBM GN that evolved into MN and briefly review the literature.     

Clinical features and outcome of patients with both ANCA and anti-GBM antibodies

BACKGROUND: Patients have been described who have both anti-neutrophil cytoplasm antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies. We have attempted to define the true prevalence of such "double positive" patients, and describe in detail their clinical features and outcome. METHODS: We have reviewed all serologic assays performed between 1990 and 2000 in a single institution, and the case notes of patients having sera positive for both ANCA and anti-GBM antibodies. During this time 20,392 sera were initially tested for ANCA, and 4808 sera tested for anti-GBM antibodies. RESULTS: Five percent of all ANCA-positive serum samples were also positive for anti-GBM antibodies, and 32% of all anti-GBM positive samples had detectable ANCA. Of 27 patients with both antibodies, 82% had anti-myeloperoxidase specific P-ANCA. Pulmonary hemorrhage occurred in 44%. Renal biopsy showed extensive glomerular cellular crescents in most patients. Patient and renal survival rates were 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis-dependent at presentation, and none of these recovered renal function, despite immunosuppression with or without plasma exchange. CONCLUSION: Serologic evidence of double positivity for both ANCA and anti-GBM antibodies is common in patients with either antibody. In our study these patients have a poor prognosis when presenting with severe disease and initially behave more like anti-GBM disease than vasculitis. Recovery from severe renal failure is rare.