应用抗肾小球基底膜抗体的中和性单克隆抗体治疗抗肾小球基底膜肾炎大鼠的实验研究

目的 应用抗肾小球基底膜（GBM）抗体的中和性单克隆抗体注射抗GBM肾炎大鼠,观察各种生化指标及肾脏病理学的变化。 方法 将Wistar大鼠随机分为5组,每组9只：(1)肾炎模型组：经尾静脉注入人抗GBM抗体;(2)正常对照Ⅰ组:经尾静脉注入非抗体性的健康人lgG;(3)对照Ⅱ组：经尾静脉注入抗GBM抗体的中和性单克隆抗体;(4)干预Ⅰ组：经尾静脉注入人抗GBM抗体,第7天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体(1.5 ml/100 g);(5)干预Ⅱ组：经尾静脉注入人抗GBM抗体,第14天后再经尾静脉注入抗GBM抗体的中和性单克隆抗体。分别在实验后第7、14、21天观察大鼠24 h尿蛋白量、BUN、Scr和肾组织病理学的变化。 结果 第21天干预Ⅰ组尿蛋白量为（16.62±5.53） g/d、BUN为（11.53±2.26） mmol/L、Scr为（102.46±16.86） μmol/L,均显著低于肾炎模型组（P < 0.05）;干预Ⅱ组较肾炎模型组也有所降低,但差异无统计学意义（P > 0.05）。干预Ⅰ组和干预Ⅱ组肾脏细胞增生、新月体的形成及免疫复合物的沉积均少于肾炎模型组,但干预I组更为明显。对照Ⅰ组和对照Ⅱ组之间无明显变化。 结论 早期应用抗GBM抗体的中和性单克隆抗体能够有效改善抗GBM肾炎大鼠的肾脏病变。     

Glomerular basement membrane type IV collagen antigens in Goodpasture's and Alport's syndromes

Type IV collagen, the main constituent of the renal glomerular basement membrane, is involved in Goodpasture's syndrome, and autoimmune disease, and in Alport's syndrome, a genetic disease. There are 6 alpha chains, α1(IV) through α6(IV), in type IV collagen in mammals. Immunohistochemical studies, using α-chain-specific monoclonal antibodies on tissue specimens from healthy people and patients with Alport's syndrome, have shown that there are 3 forms of type IV collagen molecules in mammalian basement membranes, namely α1/α1/α2, α3/α4/α5, and α5/α5/α6. Antibody specificity analysis of sera from patients with Goodpasture's syndrome show that all sera have autoantibody, with the highest titer against α3(IV)NC1, although they also have titers against the other 5α chains. This indicates that α3(IV)NC1 is the major target antigen of the disease, although the glomerular basement membrane contains the α1 through α5 chains. Experimental glomerulonephritis in rats, induced by the injection of 6 recombinant α(IV)NC1s with an adjuvant, has shown that α3(IV)NC1 and α4(IV)NC1 are nephritogenic. The lack of, or very poor, nephritogenicity of the other 4 α(IV)NC1s can be explained by the high immunologic tolerance against these chains, which are distributed widely in basement membranes of the whole body. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology,” Tokyo, May 10, 1998.     

Alport's syndrome: specificity and pathogenesis of glomerular basement membrane alterations

In Alport's syndrome (AS) thinning and splitting of the glomerular basement membrane (GBM) are assumed to be characteristic ultrastructural alterations. Both lesions are, however, non-specific because they can occur in other glomerulopathies. In addition, splitting may be found in non-glomerular structures. It should be emphasized that the characteristic lesion in AS is a result of the widespread combination of thin and split GBM in the same biopsy specimen. In our opinion the basic lesion is the thin GBM, which is characterized by a lamina densa (measuring 50–150 nm in thickness) which may begin to split as a result of focal detachment of podocyte pedicles (spacing) and repeated subepithelial deposition of new lamina densa layers. Splitting thus appears to be a secondary lesion. Thinning of GBM may represent a persistent embryonal status of the lamina densa and may thus be the result of a development defect. This assumption is supported by the findings of fetal-like glomeruli and small capillary loops in AS.     

全反式维甲酸对抗肾小球基底膜肾炎小鼠模型肾脏损害的保护作用

目的探讨全反式维甲酸对肾毒性血清肾炎(NTSN)小鼠模型的作用及机制。 方法使用肾毒性血清(NTS)尾静脉注射构建NTSN模型,设置对照组、NTS组、NTS＋维甲酸组。NTS注射前5 d给予羊免疫球蛋白和完全弗氏佐剂腹腔注射预处理,预处理后24 h给予16 mg/kg全反式维甲酸或溶媒腹腔注射,NTS注射后7 d处死小鼠。ELISA法检测小鼠白蛋白尿/肌酐比值、小鼠BUN;肾组织石蜡切片HE染色,定量分析新月体肾炎、肾小球节段硬化的百分比;肾组织冰冻切片行CD8^＋、CD4^＋、CD68免疫荧光染色,并定量分析;QPCR方法分析肾皮质炎症细胞趋化因子如人单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)、淋巴细胞趋化因子(LTN)的表达量。 结果维甲酸处理组显著减轻肾毒性血清肾炎小鼠模型的蛋白尿[NTS组和NTS＋维甲酸组尿微量白蛋白/肌酐比值(UACR)分别为：(4.52±0.36)×10^－3mg/g、(2.63±0.18)×10^－3mg/g;q＝18.45,P< 0.01]、肾功能[NTS组和NTS＋维甲酸组BUN分别为：(16.81±1.23)mmol/L、(13.33±0.62)mmol/L;q＝6.155,P<0.01]、减轻肾组织病变[NTS组和NTS＋维甲酸组含新月体的肾小球百分比分别为：[(36±1.58)%、(22.2±1.92)%;q＝21.46,P<0.01]。维甲酸处理组每低倍镜视野下CD8^＋淋巴细胞计数、CD4^＋淋巴细胞计数、每高倍镜视野下CD68阳性细胞面积较NTS组均明显减少,差异有统计学意义(q值分别为：9.545、8.610、11.08;P<0.01);维甲酸可以显著抑制炎症细胞趋化因子(MCP-1、ICAM-1、LTN)的基因表达。 结论维甲酸通过抑制炎症细胞趋化因子的表达、减少炎症细胞的浸润,减轻NTSN小鼠模型的蛋白尿、新月体形成等肾损害。     

Variants of Alport's syndrome

Variants of Alport's syndrome include mainly those associated with hereditary macrothrombocytopenia (and occasionally leukocyte inclusions) or with esophageal, tracheobronchial and genital leiomyomatosis. Within Alport's syndrome there appears to be no justification for differentiating those with nephritis and deafness from those with nephritis alone. However, in indirect immunofluorescence studies using the mouse monoclonal antibody, MCA-P1, which recognizes the glomerular basement membrane (GBM), reduced or absent binding was found in 20 of 42 cases of hereditary nephritis. Most of these showed typical ultrastructural GMB changes. These results suggest that there is probably a subset of patients characterized by typical GBM lesions and an absence, inaccessibility or abnormality of the GBM antigen recognized by MCA-P1.     

Anti-glomerular basement membrane antibody disease: a case report and a review of Japanese patients with and without alveolar hemorrhage

A 73-year-old man was admitted to our hospital because he had developed loss of appetite, abnormal behaviors, and consciousness disturbances that had begun in late February 1998. On admission, a renal biopsy was performed because of progressive deterioration of renal function, as evidenced by a serum urea nitrogen (UN) level of 109 mg/dl and a serum creatinine level of 16.3 mg/dl. Light microscopic examination showed severe cellular crescent formation with fibrin deposition in glomeruli and markedly degenerated Bowman's capsule. Immunofluorescence examination revealed linear deposits of IgG along glomerular basement membranes (GBM), and granular deposits of C3 on the GBM, as well as deposits of fibrinogen in Bowman's capsule. The patient was diagnosed as having anti-GBM antibody disease, based on negative results for myeloperoxidase (MPO)/proteinase-3 (PR-3)-anti-neutrophil cytoplasmic antibody (ANCA), high serum anti-GBM antibody titers, and the absence of pulmonary hemorrhage. He was treated with both combination therapy (cyclophosphamide and prednisolone) and plasmapheresis. In spite of the disappearance of anti-GBM antibody, his renal function did not improve, and he has been treated with regular hemodialysis since March 1998. We reviewed 49 cases of anti-GBM antibody disease in patients with alveolar hemorrhage (group A; Goodpasture's syndrome) and 39 cases in patients without it (group B) reported in Japan from 1975 to 1999, examining the differences between these groups, and we clarified the characteristics of these rare diseases in Japan. There was no difference in age, sex, and ANCA positivity between the two groups. The mortality rate was higher in group A (56.2%) than in group B (18.4%). About half of the patients underwent plasmapheresis, but it did not reduce the mortality rate or improve the renal prognosis. Received: November 20, 2000 / Accepted: November 19, 2001     

The glomerular basement membrane defect in Alport-type hereditary nephritis: absence of cationic antigenic components

Alport-type hereditary nephritis is a familial disorder which results in progressive renal insufficiency and sensorineural hearing loss. It is thought to result from a biochemical defect affecting basement membranes. To study this further, non-collagenous components of type IV collagen were prepared from the glomerular basement membrane (GBM) by collagenase digestion from three male patients with hereditary nephritis. The normal Goodpasture antigenicity of the 28 and 26 kD monomers and 54 and 50 kD dimers which may be isolated from the GBM was absent on one-dimensional immunoblots. Two-dimensional electrophoresis and immunoblotting studies showed absence of Goodpasture antigenicity of these molecular weight components as well as all cationic monomeric and dimeric spots. It is concluded that the expression of the Goodpasture antigen is altered in basement membranes of hereditary nephritis patients. The altered antigenicity thus acts as a marker for the underlying abnormality.     

Reactivity of monoclonal antibody P1 with glomerular basement membrane in thin-membrane nephropathy

A monoclonal antibody, P1, possessing antiglomerular basement membrane specificity similar to that of naturally-occurring Goodpasture antibody, was used to study renal biopsy material from patients with thin-membrane nephropathy. Immunofluorescence and immunoperoxidase techniques were employed to detect tissue localisation after sections had been incubated with P1. Staining of glomerular and tubular basement membranes in the 14 patients with thin-membrane nephropathy was similar to that in 10 subjects with various other renal diseases, whereas three patients with Alport's syndrome all gave diminished or absent staining, as has been reported previously. These observations confirm that Goodpasture antigen is present in the basement membranes in thin-membrane nephropathy and that it reacts normally with P1 antibody. They also add to the evidence that the lesions of thin-membrane nephropathy and Alport's syndrome are fundamentally different. The staining method may be used as a differential diagnostic test.     

抗肾小球基底膜病临床病理及血浆置换疗效分析

目的 分析抗肾小球基底膜（GBM）病的临床病理特点和预后;评价双膜血浆置换（DFPP）清除抗GBM抗体的有效性和安全性。 方法 回顾分析北京协和医院1999年10月至2010年5月确诊为抗GBM病的35例住院患者的临床病理资料。患者根据临床表现分为3组：组Ⅰ：24例严重肺出血或急进型肾小球肾炎（RPGN）者,接受甲泼尼龙（7.5~15 mg·kg-1·d-1,3~5 d）冲击和（或）DFPP治疗,后续以泼尼松（1.0 mg·kg-1·d-1）和（或）环磷酰胺（CTX 0.1 g/d）;组Ⅱ：5例无严重肺出血或RPGN者予泼尼松和（或）CTX治疗;组Ⅲ：5例就诊时已为终末期肾病（ESRD）和1例肾功能正常者未给予免疫抑制治疗。观察患者临床病理特点,连续监测4例患者DFPP治疗前后抗GBM抗体滴度变化情况,计算抗体的清除率。分析影响预后的相关因素。 结果 35例患者平均年龄（41.06±16.55）岁,男女比例4∶3;16例（45.7%）患者表现为Goodpasture综合征;18例（51.4%）表现为抗GBM肾小球肾炎。24例接受肾穿刺活检患者中,13例（54.2%）表现为新月体肾小球肾炎;7例患者并发其他肾小球肾炎。组Ⅰ死亡7例,50%患者肾脏长期存活。与组Ⅱ相比,组Ⅰ患者入院时Scr水平、抗GBM抗体滴度、肾小球新月体比例均显著升高（P < 0.05）;老年患者、贫血、入院时Scr水平高（>300 μmol/L)及硬化肾小球比例更高;入院时少尿或无尿、需要血液透析治疗、肾脏预后差更普遍。18例患者的94次DFPP治疗中,无明显出血、低血压;4例连续动态监测抗GBM抗体滴度的患者中,4~6次DFPP后抗GBM抗体转阴,中位清除率为55%。 结论 根据不同临床表现选择个体化的治疗方案有助于改善预后,减少并发症。DFPP能安全有效地清除抗GBM抗体。     

The effects of vitamin E on tissue oxidation in nephrotoxic (anti-glomerular basement membrane) nephritis

The effects of vitamin E on tissue oxidation, kidney function and morphology were studied in rats with nephrotoxic nephritis (NTN). Thirty-six nephritic animals received no treatment (group 1), while 36 were treated with vitamin E (group 2). Twenty-four hours after the administration of anti-glomerular basement membrane antibody, sulfhydryl-containing renal protein was significantly lower in group 1 than in group 2 (0.70±0.16 and 1.08±0.06 mmol/100 g kidney tissue, respectively), suggesting a free oxygen radical scavenging effect of vitamin E in group 2. The difference was similar on day 14. The creatinine clearance was significantly lower in group 1 than in group 2 on day 1 (40±30 and 204±60 l/min per 100 g body weight, respectively). The protein excretion was initially high in both groups, but a significant decrease was detected in group 2 relative to group 1 on day 14 (25±18 and 92±38 mg/24 h, respectively). The morphological changes were less severe in group 2. Vitamin E treatment did not alter any of the above values significantly in healthy animals. The release of oxygen free radicals in NTN might play an important role in the pathogenesis, which can be influenced by free radical scavengers through changes in kidney function and morphology.     

Urinary excretion of glomerular basement membrane-related peptides in children with renal disorders

Urinary excretion of glomerular basement membrane (GBM)-related peptides was analysed in 72 patients with a variety of renal diseases by immunoblotting using polyclonal antibodies against either collagenase or pepsin digests of human GBM. The specificity of the antibodies was verified by elution of antibodies bound to urinary GBM-related peptides on nitrocellulose blots and demonstration of reactivity of the eluted antibodies with the respective GBM digests. Furthermore, six mice immunized with urinary GBM-related peptides all developed focal linear deposits of mouse IgG along their GBM, linear and mesangial deposits of C3 in the glomeruli and serum antibodies reactive with human GBM. Monoclonal antibodies against urinary GBM-related peptides of one of the mice reacted with different peptides of the non-collagenous and collagenous domains of type IV collagen, the major structural protein of GBM. In the majority of the 75 patients' urines tested, excretion of GBM-related peptides with molecular weights of 33, 50, 80 and 150 kilodaltons (kD) was detectable. Patients with a diminished glomerular filtration rate (GFR) demonstrated excretion of the 33 kD peptide more frequently (91%) and never of the 80 kD peptide as compared with patients with normal GFR (33 kD [42%] 80 kD [87%]). The pattern of urinary GBM-related peptides was not specific for the underlying renal disease as in Alport's syndrome.     

Failure of two subsequent renal grafts by anti-GBM glomerulonephritis in Alport's syndrome: case report and review of the literature

Abstract. We describe a patient with Alport's syndrome who developed severe crescentic glomerulonephritis after each of two successive transplantations, leading to accelerated graft failure on both occasions. This complication occurred in the 7th postoperative month for the first transplant and in the immediate postoperative period for the second. Immunopathological studies of the second transplant demonstrated that the glomerular lesions were mediated by antiglornerular basement membrane (GBM) antibodies displaying the same pattern of reactivity as the MCA-P1 monoclonal antibody directed against the Goodpasture antigen. This observation indicates that the anti-GBM immunization induced by renal transplantation in some patients with Alport's syndrome may be responsible for recurrent graft failure.     

Anti-glomerular basement membrane nephritis in a 5-year-old girl

.We report a 5-year-old girl with anti-glomerular basement membrane nephritis. Her outcome was excellent with clearance of antibody and recovery of renal function 5 weeks after the start of immunosuppression and plasmaphaeresis. Received December 11, 1995; received in revised form May 16, 1996; accepted May 20, 1996     

Alport's syndrome as a cause of renal failure in Europe

We studied the geographical distribution, male to female ratio, and age at the start of renal replacement therapy (RRT) for end-stage renal failure (ESRF) in 600 patients with hereditary nephritis with nerve deafness (Alport's syndrome) reported to the European Dialysis and Transplant Association Registry since 1975. Annual age- and sex-specific acceptance rates for RRT showed a variable peak incidence according to country, ranging between, 0 and 2.4 patients per million population in males aged 15–24 years, but with only about half this incidence in females. In Scandinavian countries there were very few females who started RRT, and males were older than in the rest of Europe. The overall male to female ratio was 4:1. The median age at the start of RRT was: males (n=479) 24.3 years (1st quartile 19.5 years; 3rd quartile 31.5 years); females (n=121) 31.5 years (1st quartile 23.0 years; 3rd quartile 43.2 years). Our study provided confirmation that males reach ESRF earlier than females. In addition, we detected previously unrecognized geographical differences. Offprint requests to: S. R. Dykes, EDTA Registry, St Thomas's Hospital, London SE1 7EH, UK     

Failure of two subsequent renal grafts by anti-GBM glomerulonephritis in Alport's syndrome: case report and review of the literature

We describe a patient with Alport's syndrome who developed severe crescentic glomerulonephritis after each of two successive transplantations, leading to accelerated graft failure on both occasions. This complication occurred in the 7th postoperative month for the first transplant and in the immediate postoperative period for the second. Immunopathological studies of the second transplant demonstrated that the glomerular lesions were mediated by antiglomerular basement membrane (GBM) antibodies displaying the same pattern of reactivity as the MCA-Pl monoclonal antibody directed against the Goodpasture antigen. This observation indicates that the anti-GBM immunization induced by renal transplantation in some patients with Alport's syndrome may be responsible for recurrent graft failure.     

Clinicopathological characteristics and predictors of poor outcome in anti-glomerular basement membrane disease – a fifteen year single center experience

IntroductionAnti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis affecting the renal and lung capillary beds. We aim to study the clinicopathological characteristics and predictors of poor outcome of this disease in our population.Materials and methodsThis is a 15 year retrospective, single center observational study of Indian cohort. Patients with biopsy proven anti-GBM disease were studied.ResultsAnti-GBM disease was found in 0.5% of the total cases. The mean age at presentation was 46.7 years. Compared to renal limited disease those with pulmonary-renal syndrome had a higher frequency of hypertension, oliguria, percentage of crescents, interstitial inflammation and glomerulosclerosis. Double positive (anti-GBM and ANCA antibodies) patients showed more of glomerulosclerosis, tubular atrophy/interstitial fibrosis (IFTA) as well as periglomerular granulomas on biopsy. Patient survival at one year was 40.4% and death censored renal survival was 9.7%. Factors affecting the dialysis dependency at presentation were oligoanuria (p = .04), creatinine levels >5.7 mg/dl (p = .003), and high mean anti-GBM titers (p = .008). Atypical cases accounted for 8.3% of these patients. Oligoanuria (HR = 5.0, p = .05), high serum creatinine (HR = 1.55, p = .05), severe glomerulosclerosis (HR = 1.09, p = .03), and IFTA (HR = 2, p = .04) were associated with poor renal outcome. Advanced age (HR = 1.92, p = .03), high serum creatinine (HR = 1.9, p = .04) and high anti-GBM titers (HR = 1.01, p = .03) were associated with poor patient survival.ConclusionsAnti-GBM is a rare disease with poor prognosis and varied presentations. Patients with pulmonary-renal syndrome showed severe disease whereas double positive had more of chronic changes. The predictors of poor prognosis include advanced age, oliguria, serum anti-GBM levels, serum creatinine levels, degree of glomerulosclerosis and IFTA. Atypical anti-GBM cases should be kept in mind while evaluating renal biopsies.     

Incidence and outcome of antiglomerular basement membrane disease in Chinese

Background: Antiglomerular basement membrane (anti‐GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti‐GBM disease in Asians. To study the incidence and clinical characteristics of anti‐GBM disease among Chinese patients, we reviewed our experience of anti‐GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. Methods: All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti‐GBM antibodies were detected by either enzyme‐linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti‐GBM disease during this 11‐year period, yielding an incidence of approximately 0.6 cases per million population per year. Results: In this cohort, anti‐GBM disease predominantly affected older patients (mean age: 58.6 ± 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1‐year renal and patient survival was 15% (95% CI 0–40%) and 70% (95% CI 42–98%), respectively. Most patients presented with non‐specific symptoms as well as impaired renal function. Detection of anti‐GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long‐term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. Conclusion: Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long‐term preservation of renal function after the initial attack is unusual.     

Heparanase inhibition reduces proteinuria in a model of accelerated anti-glomerular basement membrane antibody disease

BACKGROUND: The beta-d-endoglycosidase, heparanase, is emerging as an important contributor to the pathogenesis of proteinuria. The purpose of the present study therefore was to examine the role of heparanase in a model of accelerated anti-glomerular basement disease (anti-GBM). METHODS: Accelerated anti-GBM disease was induced and animals sacrificed at day 10 to establish heparanase expression using immunohistochemistry and western blot analysis. In addition, cortex was isolated from normal and diseased glomeruli to determine if mRNA levels altered with disease. A previously validated anti-heparanase antibody associated with proteinuria reduction, in a model of membranous nephropathy, was administered prior to disease induction to establish its impact on protein excretion in this model. RESULTS: At day 10 of anti-GBM disease, an increase in glomerular heparanase was shown using immunohistochemistry. Sequential staining studies revealed that this increase was associated with glomerular endothelial, epithelial cells and invading ED-1-positive inflammatory cells. RT-PCR revealed an insignificant 1.2-fold induction of mRNA at day 10 of disease. Western blot analysis of kidney cortex confirmed that the active 58-kDa heparanase species was restricted to diseased kidney at day 10. The inactive 65-kDa precursor, however, was found only in cortex derived from normal kidney. Proteinuria at day 10 of disease was significantly reduced, in the absence of altered rat anti-sheep antibody titres, after administration of a validated polyclonal anti-heparanase antibody (P < 0.05). Furthermore, sheep IgG deposition was not altered by administration of the anti-heparanase antibody. CONCLUSION: These data suggest that heparanase contributes to the pathogenesis of proteinuria in a model of anti-GBM disease.     

Anti-glomerular basement membrane antibody disease in Japan: part of the nationwide rapidly progressive glomerulonephritis survey in Japan

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rare, but well characterized cause of glomerulonephritis. It is defined by the presence of autoantibodies directed at specific antigenic targets within the glomerular basement membrane. This pattern of rapidly progressive glomerulonephritis and alveolar hemorrhage is often referred to as Goodpasture’s syndrome. The prognosis for patients with anti-GBM antibody disease is poor. In Japan, to improve the prognosis of patients with rapidly progressive glomerulonephritis (RPGN), we conducted a nationwide survey of patients with RPGN and investigated the initial symptoms, laboratory findings including renal biopsy findings, treatment methods, and outcomes. Among patients with RPGN, patients with anti-GBM antibody disease were rare: 6.6% (47/715). Alveolar hemorrhage (Goodpasture’s syndrome) was observed in 23.4% of patients with anti-GBM antibody disease. Most patients with anti-GBM antibody disease had renal failure at the time of diagnosis. The mean serum creatinine level of patients with renal-limited anti-GBM antibody disease was 7.07 ± 4.21 mg/dl and that of patients with Goodpasture’s syndrome was 7.99 ± 4.31 mg/dl. The mean level of crescent formation was 78.99 ± 23.54% in patients with anti-GBM antibody disease, and a cellular crescent form was observed in 63.2% of those patients. The prognosis for patients with anti-GBM antibody disease is poor; the renal survival rate at 6 months after onset was 20.9%, and the mortality at 6 months after onset was 23.3%. To improve the prognosis for anti-GBM antibody disease, it may be necessary to detect this disease in the early stages and to treat it without delay. Presented at the 36th Eastern Regional Meeting of the Japanese Society of Nephrology.